One issue with using excess mortality to manage epidemics:
too many places report deaths with no urgency;
the worst may be over long before those reports are available.
CDC most recent mortality data is for 18 months ago.
for cases < 20 days, approximating contagious cases
orange
for 3 < cases < 6 days, to compare with:
red
for cases < 3 days
darker red
for new case counts greater than for (orange) previous 3 days
as well as 3 days one week previous;
to ignore fluctuations in new case counts with 7 day periodicity.
Darker red for e.g. Colleton than Washington, DC means that,
while DC may have more new cases per 100K over the most recent 3 days,
that rate is lower than for their previous 3 days (orange)
while Colleton experienced an increased case rate.
Places like NYC now approach 3% gray, and random testing suggests that
many places have about 6 times as many folks with antibodies as confirmed cases,
so New York may be approaching 20% "herd immunity". My simple computer simulation suggests that
infection rates tend to begin "naturally" decreasing above 20% immunity...
The Second COVID-19 Shot Is a Rude Reawakening for Immune Cells
Side effects are part of the vaccination process; not everyone will experience them,
but the two COVID-19 vaccines cleared for emergency use in the U.S.,
made by Pfizer/BioNTech and Moderna,
already have reputations for raising the hackles of the immune system:
In both companies' clinical trials, at least a third of volunteers
ended up with symptoms such as headaches and fatigue.
Superspreader Sunday?
Coronavirus cases in the U.S. have surged after almost every major holiday
of the past year, including Memorial Day, Labor Day, Thanksgiving and Christmas.
This weekend brings another major holiday, even if it's not an official one:
Super Bowl Sunday. And there is reason to worry that it will turn into Superspreader Sunday.
Polls show that a significant number of people plan to attend parties.
Bielefeld University scientists have for the first time
imaged SARS-CoV-2 using a helium ion microscope,
which unlike conventional electron microscopy needs not coat samples with metal,
allowing more clearly observing interactions between coronaviruses and host cells.
https://phys.org/news/2021-02-cell-virus-sars-cov-helium-ion.html
Dendritic cells, which initiate specific immune responses,
can reprogram their genes to improve their immune response.
"dendritic cells capture possible pathogenic agents in different tissues and entry sites,
process their components, and transport them to lymph nodes. Here, they establish
communication with T lymphocytes through the formation of a specialized structure
called the immune synapse. The immune synapse allows the dendritic cell
to present processed components of the infectious agent to a T cell,
so that they can be recognized and initiate a specific T cell immune response."
A collaboration led by Scripps Research has developed a way to separate beneficial
anti-inflammatory properties of a group of steroids called glucocorticoids from some
unwanted side-effects, through an optimization process named "ligand class analysis."
https://medicalxpress.com/news/2021-02-scientists-method-safety-drug-covid-.html
As of October 2020, individuals aged 20-49 are the only age groups sustaining (21 pages)
resurgent SARS-CoV-2 transmission with reproduction numbers well above one,
and at least 65% of U.S. COVID-19 infections originate from individuals aged 20-49.
https://science.sciencemag.org/content/early/2021/02/01/science.abe8372.full.pdf
As the U.S. COVID-19 vaccination campaign accelerates, governors, public health directors
and committees advising them are holding key discussions behind closed doors,
including debates about who should be eligible for the shots and how best to distribute them.
An Associated Press review found that advisory committees created to prioritize vaccinations
have been holding private meetings in at least 13 states home to more than 70 million people.
In at least 15 other states, such meetings are open to the public. But even in those states,
governors and health officials can modify or override committee recommendations
with little or no public explanation.
https://apnews.com/article/public-health-campaigns-coronavirus-pandemic-62aba0ccafbba43f1997a67fdb789bf5
Comparative evaluation of 19 reverse transcription loop-mediated isothermal
amplification assays for detection of SARS-CoV-2 (11 pages)
Based on overall detection performance, Set-4, Set-10, Set-11, Set-13, Set-14 and Set-17
that target Nsp3, S, S, E, N and N gene regions of SARS-CoV-2, respectively,
were determined to be better than other primer sets. Two RT-LAMP assays with Set-4 primers
in combination with any one of four other primer sets (Set-14, Set-10, Set-11, and Set-13)
were recommended to be used in the COVID-19 surveillance.
Coronavirus is in the air - there's too much focus on surfaces
Catching the coronavirus from surfaces is rare.
The WHO and national public-health agencies need to clarify their advice.
Late last year, the NYC MTA asked the federal government for advice on whether
to focus solely on aerosols. It was told to concentrate on fomites, too, and has so far
directed more resources towards cleaning surfaces than tackling aerosols.
Johnson & Johnson releases vaccine candidate results
It was 66% effective overall at preventing moderate and severe disease 4 weeks after the shot,
a result that covers a wide range of variation depending on geography:
it was 72% effective at protecting against moderate to severe illness in the U.S.,
but it was 66% effective in Latin America and 57% effective in South Africa, where the
new variant, known as B 1.351, made up 95% of the COVID-19 cases reported in the trial.
Maryland biotech company Novavax releases vaccine candidate midstage trial results
It was 89% effective in a UK trial, where the B.1.1.7 variant has become dominant,
and about half the infections were that variant.
It was 49% effective in their South African trial, where nearly all the participants who got sick
were infected with their variant. Excluding participants without HIV, it was 60% effective.
Novavax noted that about 1/3 of South African participants appeared to have already
been infected with the original strain of coronavirus, based on antibodies in their blood
when they were vaccinated. Some of those people became infected again,
suggesting generated immunity might not fully protect against the new variant.
All 5 vaccines with public results have eliminated COVID-19 deaths.
They have also drastically reduced hospitalizations.
They're not 100% effective. Even vaccinated people may be able to spread COVID-19.
While masks are imperfect, everyone should continue wearing them PROPERLY.
Last week, Dr. William Schaffner of Vanderbilt University told about a conversation
he had with other experts. During it, they imagined that a close relative had to choose
between getting the Johnson & Johnson vaccine now or waiting three weeks to get the Moderna
or Pfizer vaccine. "All of us said, 'Get the one tomorrow,'" Schaffner said. "The virus is bad.
You're risking three more weeks of exposure as opposed to getting protection tomorrow."
Oakland Airport now sells COVID-19 tests in vending machines
The test kits range between $130 and $150. This option won't work for destinations
requiring results upon arrival, as results take 24-48 hours to process. Additionally,
destinations such as Hawaii accept only PCR tests from a specific list of testing providers.
All international arrivals into the U.S. now require proof of a negative COVID-19 test. The
Biden administration is also "actively looking" at mandating negative tests for domestic travel.
Safety and Efficacy of the [Pfizer] BNT162b2 mRNA Covid-19 Vaccine
BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6).
Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by
age, sex, race, ethnicity, baseline body-mass index, and presence of coexisting conditions.
For cases of severe Covid-19 with onset after the first dose,
9 occurred among 21,728 placebo recipients and 1 among 21,720 BNT162b2 recipients.
Efficacy and Safety of the [Moderna] mRNA-1273 SARS-CoV-2 Vaccine
Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group
(56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3)
and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0);
vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001).
Severe Covid-19 occurred in 30 participants, with one fatality, all in the placebo group.
How coronavirus damages lung cells within 3 - 6 hours
"It was scary to see that the virus already starts to damage the cells so early during infection"
At least 18 existing FDA-approved drugs, including some originally designed to fight cancer,
can stop coronavirus in its tracks. Experimentally, five of those drugs
reduced coronavirus spread in human lung cells by more than 90%.
Based on the study's findings that SARS-CoV-2 does serious damage to cells
within hours, setting off inflammation, researchers say
there's likely not much that antiviral drugs like remdesivir can do
once infection has advanced to the point where patients need ventilators.
How does SARS-CoV-2 evade our immune defenses?
The first time that a cell meets the virus, it is the local innate immune system
inside the infected cell that must spring into action. By the time more diffuse
bloodborne signaling and other system-wide adaptive immune responses unfold, it may be too late.
Plitidepsin works better than remdesivir for treating COVID-19
Petri dish experiments found it 27.5 times as effective.
Plitidepsin inhibits production of eEF1A, a protein that is used by cells to create other proteins.
Prior research showed that the SARS-CoV-2 virus needs eEF1A to make its own proteins.
Drugs that target human proteins instead of viral proteins are far less likely
to allow the virus to build immunity to them.
Johnson & Johnson is expected to file for Emergency Use Authorization (EUA)
for its single-dose COVID-19 vaccine this week, but the shot has shown to be
significantly less effective than its Pfizer/BioNTech and Moderna counterparts
and looks to have problems tackling the virus' highly contagious South African variant.
Janssen investigational COVID-19 vaccine: Interim phase 3 clinical data analysis released
The Janssen vaccine is a recombinant vector vaccine
that uses a human adenovirus to express the SARS-CoV-2 spike protein.
It appears to be safe and effective at preventing moderate and severe COVID-19 in adults
Ad.26.COV2.S or JNJ-78436725 requires only a single injection and can be stored in
a refrigerator for months. It was reportedly 66% effective (72% in U.S.) at preventing the
study's combined endpoints of moderate and severe COVID-19 at 28 days post-vaccination
among all volunteers, including those infected with an emerging viral variant.
Engaging the spikes: heparan sulfate facilitates SARS-CoV-2 spike protein binding to ACE2
and potentiates viral infection (2 pages)
Molecular analysis identified that heparan sulfate (HS) interacts with the
receptor-binding domain (RBD) at the S1 subunit of the SARS-CoV-2 trimeric S-protein,
which facilitates the opening of S-protein conformation for ACE2 binding.
HS interacts with residues, adjacent to the ACE2-binding site at the RBD
of the S1 subunit of the SARS-CoV-2 trimeric S-protein, and this event, in turn,
promotes the opening of S-protein conformation for ACE2 binding (b) and thereby potentiates viral infection.
These results emphasized the role of HS as a "virus collector",
given its direct engagement with virus particles at the cell membrane
and subsequently facilitating the open RBD conformation (c, d).
It further explains that how besides the ACE2 expression level, HS greatly exhibits
the tissue tropism and associates with the altered susceptibility of patients.
Thrombotic complications are unrealistically frequent in COVID-19 patients. These
include cardiac thrombosis, vascular or disseminated intravascular microthromboses,
venous thromboembolism, and stroke, limb/mesenteric ischemia and therefore
frequently treated with therapeutic UFH or low-molecular-weight heparin (LMWH). Here,
Clausen et al. further identified that the anticoagulant function of heparin (lacking in HS)
is independent of its viral-inhibitory activity.
Characterization of SARS-CoV-2-specific antibodies reveals highly potent neutralizing IgA
This study provides direct evidence for the potent antiviral activity of serum-derived RBD-IgA.
Furthermore, our results show that the serum pool from COVID-19 convalescent is
more potent than individual purified RBD antibodies in terms of antiviral activities,
suggesting the presence of other antibody blocking sites on the virus
and additive effect of different antibodies,
which offering a theoretic basis for convalescent serum therapy
and combination antibody treatment strategy. (3 pages)
Laura Walker and Adimab colleagues tinkered with the structure of antibodies
isolated from a 2003 SARS-CoV infection to create ADG-2,
that was particularly effective at disabling SARS-CoV-2 in a lab dish.
https://www.nature.com/articles/d41586-020-00502-w
A systematic review and meta-analysis on
the safety and efficacy of tocilizumab in the management of COVID-19 (33 pages)
Administration of TCZ would reduce mortality risk, but there is not much difference
observed between the TCZ and standard of care(SOC)/control groups in other parameters
such as ICU admission rate, need of mechanical ventilation and length of hospital stay
(ICU and Non-ICU). On the other hand, TCZ treated subjects possess higher chances
of super-infections and pneumonia compared with SOC/control group.
More than 50 Long-term effects of COVID-19: systematic review and meta-analysis (22 pages)
A total of 18,251 publications were identified, of which 15 met the inclusion criteria.
The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed,
and 47,910 patients were included. The five most common symptoms were
fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%)
SARS-CoV-2 Seroepidemiology in Children and Adolescents (27 pages)
In 1038 Northern VA children, the anti-SARS-CoV-2 total antibody positivity rate was 8.5%.
66% of seropositive children had no symptoms of COVID-19.
SARS-CoV-2 infection rate was higher compared to adults in the same region at a similar time.
Contrary to prior reports, children shoulder a significant burden of COVID-19 infection.
How well do face masks protect the wearer compared to public perceptions? (6 pages)
Two methodologies were used in this study: quantitative fit testing of various face masks
to indicate their effectiveness and a survey of 710 US residents about their perceptions
of face mask effectiveness. Fabric masks blocked between 62.6% and 87.1% of fine particles,
whereas surgical masks protected against an average of 78.2% of fine particles.
N95 masks blocked 99.6% of fine particles. Survey respondents tended to underestimate
the effectiveness of masks, especially fabric masks.
New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19 (78 pages)
SARS-CoV-2 causes development of new-onset IgG autoantibodies
in a significant proportion of hospitalized COVID-19 patients
and are positively correlated with immune responses to SARS-CoV-2 proteins.
Beyond the new normal:
assessing the feasibility of vaccine-based elimination of SARS-CoV-2 (25 pages)
Vaccines that do not prevent infection allow extensive endemic SARS-CoV-2 spread
upon a return to pre-pandemic social and economic conditions.
Vaccines that only reduce symptomatic COVID-19 or mortality
will fail to mitigate serious COVID-19 mortality risks,
particularly in the over-65 population,
likely resulting in hundreds of thousands of US deaths annually.
For partially-effective vaccines to play a positive role in SARS-CoV-2 elimination,
other stackable (complementary) interventions must be deployed simultaneously.
Why Vaccines Might Not Be Able to Eliminate Covid-19
It's not known
what level of immunity is required
whether vaccines will be potent enough to achieve it
whether evolving variants may escape immunity
Since SARS-CoV-2 is thought to persist in nature in horseshoe bats
and has been known to infect minks, cats, gorillas and other animals,
wiping out the virus would require banishing it from every susceptible species
4 reasons we're seeing these worrying coronavirus variants now
genetic diversity increases over time
evolving in response to increasing immunity
low probability things are more likely in larger populations
variations accumulate in chronically infected patients, with treatments favoring some
How KN95, N95 and KN94 masks differ
N in N95 stands for National Institute for Occupational Safety and Health,
a U.S. standard certified by only one lab that is part of the CDC
FFP2 is an American Society for Testing and Materials standard "nearly equivalent" to N95
KN95 is a Chinese standard that is close to the U.S. standard
KF94 is a Korean standard
"The problem with KN95 and KN94s is that there are a lot of imposters on the market"
The first 22M Americans have been vaccinated for COVID-19,
and initial safety data shows everything is going well, CDC says.
[ Recall the drunkard who decided he could fly and jumped off a skyscraper?
On his plunge to the ground, he kept repeating "so far, so good". ]
Everyone who experienced an allergic response has been treated successfully,
and no other serious problems have turned up among the first 22 million people vaccinated,
according to the Centers for Disease Control and Prevention.
Duration of Culturable SARS-CoV-2 in 21 Hospitalized Patients
The median time from symptom onset to viral clearance in culture was 7 days.
The latest positive viral culture was 12 days after symptom onset.
Median time from symptom onset to viral clearance on real-time RT-PCR was 34 days.
The antiviral drug plitidepsin is between 10 and 100 times more effective
against SARS-CoV-2, including the new UK variant, than NHS-approved remdesivir,
finds new preclinical research involving UCL scientists.
"by targeting a host (human) protein, the effectiveness of plitidpesin
will not be altered by mutant variants in SARS-CoV-2."
Peptide Ac2-26: a way to lower stroke risk in sickle cell patients
opens a gateway of potential treatments for inflammation
and clotting stemming from conditions such as COVID-19.
The Dogs Trained to Sniff Out COVID-19
Images from Russia, England, Chile, Australia, Iran, Finland, and more countries,
where these canine COVID-19 detection programs are being developed.
Optimized primers and reaction conditions for high performance,
direct rapid colorimetric RT-LAMP SARS-CoV-2 testing (6 pages)
Set-up requires only a pipette and tips, a transfer pipette, a mini heat block, and a box of ice.
100% specificity, 85% positive percentage agreement. For use as a point-of-care test
where transport is not needed, a more basic buffer such as HBSS
or direct placement of swabs into the master mix reaction buffer
could make this process simpler, faster and more sensitive.
CRISPR-wielder Mammoth Biosciences will team up with Agilent Technologies
to help launch its upcoming high-throughput CRISPR-based DETECTR assay,
which uses Cas12 enzymes to identify and tag specific SARS-CoV-2 genomic sequences
and provides a visual result that can be read by a machine. The two companies hope
to increase the test's throughput speed even more by connecting it with Agilent's
automated liquid handling systems and sample readers. Dubbed DETECTR BOOST,
the platform aims to process about 1,500 samples over an eight-hour shift.
THE AIRBORNE CONTAGIOUSNESS OF RESPIRATORY VIRUSES
A COMPARATIVE ANALYSIS AND IMPLICATIONS FOR MITIGATION (25 pages)
Quanta emission rate (ERq) estimates were compared to values reported in literature for
SARS-CoV-1, SARS-CoV-2, MERS, measles virus, adenovirus, rhinovirus,
coxsackievirus, seasonal influenza virus and Mycobacterium tuberculosis (TB).
Median standing and speaking ERq estimate for SARS-CoV-2 (2.6 quanta / hour)
is similar to active, untreated TB (3.1/hr), higher than seasonal influenza (0.17 quanta/hr),
and lower than measles virus (15 quanta/hr). In congregate settings,
current ventilation standards are unlikely to control the spread of viruses
with upper quartile ERq values above
10 quanta/hr, such as SARS-CoV-2, indicating the need for additional control measures.
Why it takes 2 shots to make mRNA vaccines do their antibody-creating best
- and what data shows on delaying the booster dose
The first dose primes the immune system and introduces the body to the germ of interest,
allowing the immune system to prepare its defense. The second dose, or booster,
provides the opportunity for the immune system to ramp up the quality
and quantity of the antibodies used to fight the virus.
L.A. HOSPITAL VACCINATES OLDER RELATIVES OF HOUSEKEEPING STAFF
The inclusion of elderly relatives of hospital housekeepers, cafeteria and warehouse workers
came amid a chaotic push across the county and state to quickly get the vaccine
to at-risk groups to stem the relentless rise of COVID infections.
Biden said the U.S. government was nearing a deal with Pfizer and Moderna to increase
its order of vaccine doses from 400 million to 600 million by the end of the summer,
but this may not accelerate the current pace of vaccination for a few months.
States will be getting a total of 10 million doses a week instead of 8.6 million,
at least for the next 3 weeks
Regeneron has provided preliminary evidence that proactively infusing healthy people
with monoclonal antibodies against SARS-CoV-2 prevents them from developing
noticeable symptoms of COVID-19 if they are exposed to the coronavirus.
Eli Lilly previously released similar results for its monoclonal antibody.
While monoclonals work immediately and presumably would be effective
in people who don't mount strong immune responses after being vaccinated,
they are expensive and must be infused, but supply is much larger than demand.
https://www.sciencemag.org/news/2021/01/monoclonal-antibodies-protect-against-covid-19-second-study
Vaccine 2.0: Moderna and others plan tweaks to protect against new coronavirus mutations
A study by virologist David Ho of Columbia University,
under review at Nature and posted as a preprint on bioRxiv,
found that the serum of 22 people vaccinated with Moderna's vaccine
or a similar one from Pfizer was six to nine times less potent against B.1.351,
and serum from 20 previously infected people was 11 to 33 times less potent.
Researchers in South Africa, meanwhile, have found that antibodies from
6 recovered patients were 6 to 200 times less effective at neutralizing B.1.351
As California lifts restrictions,
a top L.A. health official worries about coronavirus variants and the slow vaccine supply
Los Angeles County receives over 168,000 doses of the vaccine weekly, but that
chips away too slowly at the more than 2 million people currently eligible to be vaccinated.
In an article published Tuesday in JAMA Network, CDC researchers wrote that
wearing masks and maintaining social distance are effective
at limiting coronavirus transmission in schools,
but activities such as indoor sporting events promote spread and should be diminished.
https://jamanetwork.com/journals/jama/fullarticle/2775875
COVID-19 can cause worse lung damage than smoking
"I don't know who needs to hear this, but 'post-COVID' lungs
look worse than ANY type of terrible smoker's lung we've ever seen"
Chest X-rays of asymptomatic patients exhibited a severe chest X-ray 70-80% of the time,
but those with COVID-19 symptoms had one every time.
Organizers of a 1,000-person New Year's Eve party
that was going to be held on the Yorktown aircraft carrier at Patriots Point are suing the state-owned museum's board
for not allowing it to take place because of COVID-19 concerns.
Can Biden fix the vaccine mess? An expert says yes
To beat COVID-19, we will have to pay for deferred public health infrastructure.
Cash-strapped states have been ill-prepared to distribute and administer vaccines.
Men are 1.7 times more likely than women to die from COVID-19 (3 pages)
X chromosomes are rich in genes that regulate immune response.
Estrogen can help suppress ACE 2, used by SARS-CoV-2 to enter cells.
Male hormone androgen appears to enhance the ability of the virus to infect cells.
As men in their early 60s begin to lose ability to mount an initial immune response,
often there is a compensatory overreaction by other immune system molecules
that can lead to damaging inflammation which can trigger so-called "cytokine storms".
A new SYBR Green real-time PCR to detect SARS-CoV-2 (11 pages)
A more affordable and swift methodology for negative SARS-CoV-2 screening
can be applied on a large scale.
The TaqMan methodology uses an additional labeled probe to SYBR Green detection,
significantly increasing sensitivity and specificity of the assay
due to the reporter dye's conjugation to the specific oligonucleotide
sequence of the probes, which is capable of emitting fluorescence.
Logistic advantage of two-step screening strategy for SARS-CoV-2 at airports (18 pages)
Point of care testing by quantitative chemiluminescent enzyme immunoassay (CLEIA)
using self-collected saliva is less labor-intensive and yields results rapidly,
thus suitable as an initial screening test. Reserving nucleic acid amplification tests
for CLEIA indeterminate cases may prevent compromising accuracy while
significantly improving logistics of administering large venue mass-screenings.
UConn professor of geography Peter Chen has published a study in the January 2021
issue of the International Journal of Geographical Information Science
outlining a comprehensive predictive model for COVID-19 in every Connecticut town
based on travel behaviors by adding in social distancing metrics and residents'
travel activities to the traditional SEIR epidemiological model. (21 pages)
https://www.tandfonline.com/doi/full/10.1080/13658816.2021.1873999
Moderna making booster shot to fight COVID-19 variants
Moderna is testing two booster-shot options
- one specifically aimed at the South African variant
and another to broadly fight new mutations.
Laboratory research using blood from people and monkeys
who had received the company's vaccine found that
the U.K. variant did not appear to reduce neutralizing antibodies production,
but the South African variant showed a sixfold reduction.
Newsom cancels California's COVID-19 stay-at-home orders
[ last I knew, ambulances could not unload at L.A. hospitals..?]
Compared to when the governor established the stay-at-home order framework last month,
total confirmed cases have more than doubled, daily confirmed cases have increased,
7- and 14-day positivity rates are higher and ICU capacity is lower
in each region of the state except Northern California,
according to the most recent state data available.
Merck ends COVID vaccine program, citing inferior immune responses
Merck said it will focus COVID-19 research and manufacturing efforts
on two investigational medicines: MK-7110 and MK-4482,
which it now calls molnupiravir, an oral antiviral
being studied in both hospital and outpatient settings.
Results from a phase 3 study of MK-7110, an immune modulator
being studied as a treatment for patients hospitalized
with severe COVID-19, are expected in the first quarter.
New Zealand's first case in more than 2 months is the South African variant
A 56-year-old New Zealander, who recently returned from Europe,
tested positive on Saturday to the infectious strain,
10 days after she completed her compulsory two weeks in isolation.
The woman is thought to have been infected during quarantine by a person
on the same floor of the hotel who tested positive two days before the woman left.
Adagio Therapeutics today published in vitro and in vivo data in Science
on its lead antibody candidate, ADG2, which demonstrated similar or higher potency
against SARS-CoV-2 compared to other monoclonal antibodies (mAbs) in clinical development
and strong binding to all known SARS-CoV-2 variants. It has the potential
to protect against common circulating SARS-CoV-2 variants
as well as future SARS-related viruses with pandemic potential.
https://medicalxpress.com/news/2021-01-preclinical-coronaviruses-antibody.html
The paper (12 pages)
Protective efficacy of a SARS-CoV-2 DNA vaccine in Syrian hamsters (7 pages)
A SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection,
nCoV-S(JET), elicited neutralizing antibodies in hamsters
and was protective in both wild-type and transiently immunosuppressed hamster.
Maybe not:
Vitamin D deficiency associated with increased COVID-19 risk
according to a study published in the April issue of Nutrition.
Researchers found that compared with patients with no deficiency,
those with vitamin D deficiency were 4.6 times more likely to be positive for COVID-19.
Mask adherence and rate of COVID-19 across the U.S. (9 pages)
Fourteen of 15 states with no mask-wearing policy for the general public
reported a high COVID-19 rate. Of the 8 states with at least 75% mask adherence,
none reported a high COVID-19 rate. States with the lowest levels of mask adherence
were most likely to have high COVID-19 rates in the subsequent month,
independent of mask policy or demographic factors.
Undercounting of COVID-19 deaths is greatest in pro-Trump counties
787 counties with more than 20 COVID-19 deaths from Feb. 1 to Oct. 17
reported 199,124 official COVID-19 deaths in that time period,
but an additional excess 88,142 deaths weren't attributed to the virus.
COVID-19 Vaccine Rollout Has Been Slow And Chaotic. Here's How That Could Change.
The U.S. is averaging around 970,000 COVID-19 vaccine shots a day, according to the CDC.
At that rate, the country's 330 million people will see nearly 2 more years pass
before everyone gets their second shot of the authorized vaccines.
[ Keeping in mind that data supports immunity by vaccination for 5-8 months ]
OWS and the CDC decided to pump out COVID-19 vaccines through the agency's
long-running Vaccines for Children Program, expanding its contract
with McKesson Corporation, which distributes 150 million flu shots
to public health clinics, hospitals, doctors' offices, nursing homes, pharmacies,
and other medical facilities every year. Rather than re-create a mass vaccination system,
OWS officials explained in September that the partnership would leverage
the infrastructure of the CDC's existing flu shot program through "microplans"
with 64 separate states, territories, and jurisdictions.
The CDC's Advisory Committee on Immunization Practices prioritized
long-term care facilities and nursing homes, with some 3 million staffers and older people.
To reach this population outside of a hospital setting, OWS turned to Walgreens and CVS,
which would together partner with some 75,000 nursing homes and facilities. After a slow start,
pharmacists have administered more than 1.9 million doses in these settings.
Walgreens said it would wrap up its shots by Jan. 25. Meanwhile, because OWS left
the final say in priority groups to governors, "vaccine tourism" is now a thing,
with people flying to Florida to get a shot after Gov. Ron DeSantis
opened vaccinations to people older than 65. Trump's HHS secretary Alex Azar
called for disregarding the CDC's recommendations by lowering the priority age to 65
and including people with high-risk conditions, an expansion of almost
110 million people who would be eligible for shots,
but OWS had already been shipping its entire allotment
and not holding back a reserve, leaving no extra doses for those who were now eligible.
As a result, there have been shortages in California, Ohio, Florida, and other states,
as well as canceled appointments for shots in places like New York City,
even as CDC data suggests that 19 million doses are sitting on shelves,
still awaiting injection. [hopefully freezer shelves]
Mitch McConnell bottled up federal money for strapped states
to administer vaccinations in a $900 billion coronavirus relief bill until just before Christmas.
That may have cost Republicans Senate control (when the relief bill's $600 checks
became an issue in Georgia's runoff races), and it also hobbled states' vaccination efforts.
States only received $3 billion for vaccinations when the bill passed
- half of what Redfield had suggested - piped into the CDC's Vaccines for Children Program.
Biden's plan is built around added federal support from the CDC and FEMA,
which will help build mass vaccination centers that would directly move the federal government
into the vaccine administration arena neglected by OWS.
Plan money would hire 100,000 public health workers
and pay for community health centers and mobile vaccination centers
to reach disadvantaged communities hit hardest by the pandemic.
(The U.S. now has only about 136,000 full time local public health workers.)
Walmart, which had already been providing inoculations to eligible people in New Mexico
and Arkansas, will broaden the effort to select stores in Georgia, Indiana, Louisiana,
Maryland, New Jersey, South Carolina and Texas, a Walmart representative said Friday.
The company will also offer vaccinations in Chicago and Puerto Rico. State rules apply.
In Georgia, adults ages 65 and over are eligible, but non-healthcare essential workers are not.
https://www.cnn.com/2021/01/22/business/walmart-covid-vaccine
2 in 5 Americans live where COVID-19 strains hospital ICUs
According to data through Thursday from the COVID Tracking Project,
hospitalizations are still high in the West and the South,
with over 80,000 current COVID-19 hospital patients in those regions.
[ includes U.S. map color-coded for ICU capacity]
The S.C. Department of Health and Environmental Control on Jan. 15
told the S.C. Hospital Association that medical centers would get
only 20-25% of the Pfizer doses they requested for first shots this past week
Dr. Brannon Traxler, DHEC's interim director of public health, told reporters Wednesday
that South Carolina typically gets 63,000 first doses every week,
and she doesn't expect that to change any time soon.
Weekly distribution among counties and hospital systems will vary
and there's no way to tell what's ahead.
https://www.islandpacket.com/news/coronavirus/article248646870.html
Vaccine trials being conducted in South Africa by Novavax and Johnson & Johnson
will provide more real-world data on how the vaccines perform
against the new variant there. Results are expected within a few weeks.
https://www.nytimes.com/live/2021/01/24/world/covid-19-coronavirus
A Canadian research press release raised hopes that
treating people recently diagnosed with COVID-19 with colchicine,
a drug commonly used to treat gout, could reduce the risk
they will need to be hospitalized,
but data provided were too limited to support conclusions.
https://www.statnews.com/2021/01/23/colchicine-gout-drug-shows-promise-for-covid-19/
Optimizing age-specific vaccination (4 pages)
Although vaccination of younger adults is projected to avert the greatest incidence,
vaccinating older adults will more effectively reduce mortality.
Fauci said in remarks at the White House that Johnson & Johnson
would have enough data on its vaccine to begin analysis in as soon as a week or two.
J&J had previously said it would have a first chance to review data
from its late-stage trial of 45,000 volunteers in the last week of January
or the first week of February, consistent with Fauci's timeline. From there,
J&J would need one to two weeks to analyze the data and prepare documents
for regulators in the U.S. and elsewhere seeking emergency-use authorization,
if the data demonstrates the shot's safety and efficacy,
Chief Scientific Officer Paul Stoffels told Bloomberg on Jan. 12.
Stoffels said he expects the vaccine won't be authorized
by the U.S. Food and Drug Administration until March,
with perhaps enough vaccines for 100 million Americans by this April.
Colorado will no longer use Curative COVID-19 tests at residential care facilities,
correctional facilities, shelters and other congregate care settings
after further warnings from the U.S. Food and Drug Administration
about false negatives with the tests and issues with the test's assay.
715,619 Curative tests had been performed in Colorado as of Jan. 19.
Cases involving the B.1.1.7 UK variant are increasing 70% a week in Denmark,
despite a strict lockdown, according to Denmark's State Serum Institute,
a government agency that tracks diseases
and began sequencing every positive coronavirus test to check for mutations.
By contrast, the U.S. is sequencing 0.3% of cases.
"If you just look at the reproduction number,
you just wouldn't see that it was in growth underneath at all"
Some COVID-19 Strains Are Spreading Faster Than Others
viruses furthest from the centre carry more mutations.
One change in the spike, called N501Y, arose independently in all three variants,
as well as in immunocompromised patients studied in the U.S. and UK.
Other changes in the spike (e.g. E484K, del69-70) are seen in two of the three variants.
N95 masks
Earlier this week, Germany and France mandated that all citizens wear high filtration masks
like the N95 in all public places. Some experts like Brigham Women's Hospital
and Harvard Medical School physician Dr. Abraar Karan have been advocating
for public use of N95 masks from the start of the pandemic.
Pfizer ships fewer COVID vaccine vials to U.S. after Trump FDA label change
Same amount of vaccine pepr vial, but rated for 6 instead of 5 shots, so only 5/6 as many files.
But without enough specialized syringes capable of extracting 6th dose,
Pfizer's decision likely means that the U.S. will have fewer usable doses.
Problems with Evidence Assessment in COVID-19 Health Policy Impact Evaluation
(PEACHPIE): A systematic strength of methods review (28 pages)
This study systematically assessed the currently published COVID-19 policy impact literature
for a checklist of study design elements and methodological issues.
Of 102 articles identified as potentially meeting inclusion criteria,
36 published articles evaluated the quantitative impact
of COVID-19 policies on direct COVID-19 outcomes.
Nine studies were set aside due to inappropriate study design.
20/27 met criteria for graphical display of data, 5/27 for functional form,
19/27 for timing between policy implementation and impact,
and only 3/27 for concurrent changes to the outcomes.
Only 1/27 studies passed all of the above checks,
and 4/27 were rated as overall appropriate.
Simulating the impact of different vaccination policies on the COVID-19 pandemic in New York City (15 pages)
Across all scenarios tested here, delaying the 2nd vaccine dose
leads to the largest reduction in severe epidemic outcomes (e.g. hospitalizations and deaths).
Therefore, to protect as many people as possible, this strategy
should be considered if rapid increases in infections, hospitalization
or deaths and/or shortages in vaccines were to occur.
COVID-19 vaccine supply is running low. Here's how Biden hopes to fix that
Use the Defense Production Act to produce so-called low dead space needles,
which are needed to extract a sixth dose of Pfizer's vaccine from the vial,
and increase the supply of the lipid nanoparticles needed to make all mRNA vaccines
- the category that both Pfizer and Moderna's products fall into.
IgA dominates the early neutralizing antibody response to SARS-CoV-2 (11 pages)
Serum antibodies effective against SARS-CoV-2 come in several flavors AKA isotypes:
immunoglobulin M (IgM), IgG and IgA, where IgA comes in both monomeric and dimeric forms.
Dimeric IgA antibodies, formed by covalent linkage of two individual IgA monomers,
are predominantly found in mucosal tissues, including the upper respiratory tract
where SARS-CoV-2 is first encountered. IgA serum concentrations peak 3 weeks
after symptom onset but persist 49 to 73 days post-symptoms in saliva,
and serum IgA is more potent than IgG in neutralizing SARS-CoV-2.
IgA antibodies are often detectable before the appearance of SARS-CoV-2-specific IgG.
Dimeric IgA antibodies neutralized SARS-CoV-2 more effectively than their monomeric counterparts.
Thus, vaccines that induce dimeric IgA antibodies at mucosal surfaces
may be good candidates for protection against SARS-CoV-2. (13 pages)
https://stm.sciencemag.org/content/13/577/eabf1555.full.pdf
Eli Lilly said Thursday its antibody drug can prevent COVID-19 illness
in residents and staff of nursing homes and other long-term care locations,
in a first major study involving more than 1,000 residents and staff.
"So this should not be seen in any way as competition to vaccines.
It should be for when it's too late, when there's an outbreak and people are getting exposed
and there's not going to be time for a vaccine to work."
Biden "absolutely remains committed" to invoking the Defense Production Act
to bolster supplies, directing agencies to use wartime powers to require U.S. companies
to make N95 masks, swabs and other equipment to fight the pandemic.
The executive order, called "A Sustainable Public Health Supply Chain," will also
"direct the development of a new Pandemic Supply Chain Resilience Strategy"
in an effort to bolster domestic manufacturing of critical supplies.
CA decides to use lot paused for allergic reactions from 330,000 Moderna vaccine batch
"We had further discussions with the County of San Diego Department of Public Health,
the FDA, CDC and manufacturer, and found no scientific basis to continue the pause.
Providers that paused vaccine administration from Moderna Lot 41L20A can immediately resume."
7 of the biggest coronavirus vaccine myths
vaccines unsafe because developed too fast
mRNA vaccines alter human DNA
need not mask after vaccination
no need to vaccinate after COVID-19
COVID-19 infection from vaccine
--
vaccines affect fertility: "no evidence"
pregnancy safety: CDC sez limited data
While other coronavirus parts continue to evolve,
the stem-loop II motif section of the viral RNA "is normally like a rock.
And for the virus to cause disease, it needs to keep replicating inside the human body.
So we are looking at this section of the RNA as a possible target for an antiviral."
Work focused on a single nucleotide, how it differs between the two outbreaks,
and where it might make the RNA motif vulnerable to attack.
Nucleotides are organic molecules that are the building blocks of nucleic acids,
and thus of RNA and DNA. "Using complementary biochemical and computational methods,
we determined that the structural flexibility of this important noncoding RNA motif
differs compared to that in the early 2000s SARS-CoV outbreak by only a single nucleotide change.
We also identified FDA-approved drugs that bind the RNA motif and alter its flexibility.
This was an exciting observation since the structure and flexibility
of noncoding RNA affects its function, indicating that it may be possible
to develop anti-viral therapeutics that specifically target this RNA motif
and disrupt its function."
S.Africa virus strain 501Y.V2 poses 're-infection risk'
In a new study, which has not yet been peer reviewed,
researchers in South Africa tested the variant found there, called 501Y.V2,
against blood plasma from recovered COVID-19 patients.
They found that it was resistant to neutralising antibodies
built up from prior infection, but said more research was needed
into the effectiveness of other parts of the immune response.
Biden will sign executive orders creating a National Pandemic Testing Board
to improve U.S. coronavirus testing capacity and a COVID-19 Health Equity Task Force
to ensure an "equitable" pandemic response and recovery.
Another executive order will enhance collection, production, sharing
and analysis of pandemic data. He will direct FEMA to offer
full reimbursement to states for the cost of National Guard personnel
and emergency supplies such as PPE for schools.
Strategy for Evaluating the Long-Term Efficacy of COVID-19 Vaccines (22 pages)
A valid and efficient approach to evaluate the potential waning efficacy
of a COVID-19 vaccine is developed for use with a "blinded crossover"
where placebo recipients are vaccinated in a timely manner
while still making it possible to assess long-term safety and efficacy.
Patients are not getting monoclonal antibodies, corticosteroids and other COVID-19 treatments
[ in Business news ]
Doctors say these drugs have helped them save lives, putting them in a far better position
than they were last year, but hospitals still struggle to get them administered,
and to get patients to the hospital in time to take advantage of them. In particular,
they noted last week that less than 25% of available monoclonal antibodies doses have been administered.
SC lawmaker fights COVID measures and mask rule he calls 'test vote' for state mandate
Townville republican Jonathon Hill doubts that masks prevent COVID-19 from spreading,
and he doesn't trust vaccinations for the virus. Anderson and Greenville approved mask mandates,
but success of those measures was hampered by the failure of officials in their respective counties to take similar steps
A preliminary study by researchers from BioNTech and Pfizer found their vaccine to be effective against the UK B.1.1.7 variant.
Previous preliminary research from Pfizer/BioNTech released earlier this month
found the vaccine was effective against mutation N501Y common to the virus variants
found in Britain, South Africa and Brazil. Yet another mutation, known as E484K
and present in variants detected in South Africa and Brazil but not the one from Britain,
has experts particularly worried about immunity "escape".
Apple Watch can predict COVID-19 infection, based on heart rate changes,
a week before other symptoms appear
COVID-positive individuals tend to show less variation in time between heartbeats
81% of those tested positive for COVID-19 experienced resting heart rate changes
sometimes up to nine and a half days before developing symptoms.
New U.S. COVID-19 cases declined 11% from peak last week
1.5 million new COVID-19 cases in the past seven days
Over the past month, the number of new cases recorded each day
has ranged from nearly 101,000 to more than 302,000
"Biologically speaking, nothing is changing."
42 SC Publix pharmacies start COVID-19 vaccine appointments
Vaccinations are provided by appointment only. Appointment scheduling started Tuesday at
https://www.publix.com/covid-vaccine/south-carolina
with administrations starting Wednesday.
"All available COVID-19 vaccine appointments at Publix Pharmacy have been claimed.
Additional appointments will be announced as Publix receives more inventory."
Most reliably actionable U.S. pandemic data at risk
Since July, hospital admissions data have been routed through the Department of Health and Human Services,
but some CDC officials are trying to regain control. It might seem obvious
that the CDC, traditional repository of infectious-disease information,
should win this intragovernmental battle, but the current HHS-run system works
- unlike much else - and with these data flowing in,
the federal government can dispatch help to hospitals that need it.
A small clinical trial provides encouraging results on ivermectin for reducing mild COVID-19
[ previously reported, now published by The Lancet ]
A single dose of ivermectin or placebo to 24 patients with confirmed infection
and mild symptoms, within 72 hours after first symptoms. After a week,
mean viral load in the ivermectin-treated group was lower
(around 3x lower at 4 days and up to 18x lower at 7 days post-treatment),
although the difference was not statistically significant.
Treated patients also showed reduced duration of certain symptoms
(of 50% for loss of smell and taste and of 30% for cough).
Ivermectin may act through mechanisms not involving anti-inflammatory effects.
Many COVID-19 papers cite retracted papers
Two retracted COVID-19 papers, one in The New England Journal of Medicine (NEJM)
and the other in The Lancet, were based on what appeared to be
a huge database of patient records compiled from hospitals worldwide by Surgisphere.
The 22 May 2020 Lancet paper about hydroxychloroquine and the 1 May NEJM article
about blood pressure medicine were retracted on 4 June, but 105 of 200 papers
examined by "Science" after those retractions inappropriately cited one of the disgraced studies.
Many authors copy and paste lists of apparently relevant citations
from similar papers without actually reading them. "It's frightening. It's terrible, but common."
Joggers and cyclists should wear masks - here's why
A passing jogger breathes heavily, generating exhalations with much higher momentum
than occurs with resting breathing. Heavy breathers emit turbulent gas clouds
in which are suspended droplets and microdroplets of different sizes,
some of which are carried considerably farther than two metres.
Hilton Head, Coastal Carolina hospitals cancel 300 appointments due to vaccine shortage
All appointments scheduled to take place before noon Wednesday at Hilton Head Hospital
or Coastal Carolina Hospital will be rescheduled. Appointments scheduled for noon Wednesday,
all day Thursday or all day Friday will remain the same.
[ my Jan 22 appointment should be OK ]
Neuropilin-1 (NRP1) as an alternate SARS-CoV-2 host cell entry mediator
[ suggested in Oct 20 paper ]
In these two recent studies, the NRP1-enhanced SARS-CoV-2 infectivity in human cell cultures
was inhibited by utilizing a monoclonal blocking antibody against the extracellular NRP1 b1b2 domain
or a small-molecule, selective NRP1 antagonist which binds the CendR-binding b1 domain/pocket
Rebekah Jones, who helped build the state of Florida's first COVID-19 data reporting system,
has been in a legal fight with the state in connection to her firing in May
and her turn as a whistleblower who says she was fired for refusing to manipulate the state's coronavirus data.
A warrant has been issued for Jones' arrest. She had been accused of having breached
and illegally accessed an emergency messaging alert system on Nov. 10
to send a group text encouraging users
to voice concerns about Florida's handling of the coronavirus.
Jones said Saturday that authorities have failed to find evidence that
she was behind the text and her arrest is related to other documents in her possession.
Jones said an agent informed her lawyer there would only be one charge
though more could follow if she spoke to the media.
"All of this just to silence a critic of a governor who failed to do his job
and got thousands killed," she said.
COVID-19 exposure on flights is more common than most believe
The U.S. doesn't share details,
but Canada does
From the start of the coronavirus pandemic in March through early January,
the Public Health Agency of Canada has identified potential exposure on more than 1,600 international flights
and more than 1,400 flights within Canada, for a total of more than 3,000 flights,
including nearly 200 in the past two weeks alone.
The CDC has revealed little information on the scope of COVID exposure on flights
except to release, when requested, the number of affected flights.
The latest tally: more than 4,000 flights within and into the U.S.
Facing vaccine shortages and rising infections, Biden announces vaccination blitz
that promises mobile COVID-19 inoculation sites,
National Guard troops and a federal push to increase production of the shots.
Supplies will be scarce for the next several months, making a dire situation even more chaotic.
The shortage is already bearing down on New York City, once the center of the epidemic.
Mayor Bill de Blasio said the city would run out of doses soon.
FDA stooge plays vaccination blame game with states
Azar cited the timing of the vaccine's approval
and the approach of some governors in distributing it for the delays..
New York announced Saturday that although 7 million New Yorkers are now eligible for
the coronavirus vaccine, the state is only expected to receive 250,000 doses next week.
The South Carolina Department of Health and Environmental Control says
a problem that affected the number of new cases reported has been corrected.
Saturday's report included test results of 20,694 individual results
with a 22.6% positive rate, up from 16.5% on Friday.
When correcting for the incomplete case counts,
DHEC said Jan. 8 stands as the highest single-day record in new cases,
with 6,824 positive confirmed cases.
Since DHEC is now reporting case counts on a 48-hour delay,
that total should have been reported last Sunday.
https://www.live5news.com/2021/01/16/sc-reports-more-than-new-covid-cases-systems-issue-resolved/
Moderna's CEO said its vaccine might offer protection for "a couple of years."
In December, Moderna provided optimistic news in a letter
to the editor published in The New England Journal of Medicine.
The company examined neutralizing antibody levels in 34 phase 1 participants
three months after receiving the second dose of vaccine.
Levels declined slightly, as expected, but remained higher than those of recovering patients.
Washington University School of Medicine in St. Louis has shown
a relatively simple and rapid blood test that predicts - within a day of hospital admission -
which COVID-19 patients are at highest risk of severe complications
using mitochondrial DNA levels.
https://medicalxpress.com/news/2021-01-rapid-blood-covid-patients-high.html
Beaufort Memorial Hospital to cancel 6,000 vaccinations due to shortage
[magic arithmetic: 2,000 - 450 = 6,000]
"The cancellations are necessary because the hospital placed an order
for 2,000 doses of the Pfizer-BioNTech vaccine to be delivered early next week,
but was notified Friday it will receive just 450 doses."
On Friday night, Beaufort Memorial closed its vaccine call center.
SC seniors welcome being eligible for shots; getting one is a numbers game
As of Friday, South Carolina had received 236,250 doses of COVID-19 vaccines
since mid-December for eligible people outside of long-term care facilities,
where shots are handled through a federal contract with CVS and Walgreens.
Hospitals, the only place to get a Pfizer shot, had doled out 134,580
doses by Friday morning. 140,369 additional people had made an
appointment to get a shot, according to DHEC data.
That means every dose South Carolina had received, plus nearly 38,700
doses from future shipments, were either in someone's arm or already
reserved. For the foreseeable future, South Carolina expects roughly
63,000 to 64,000 doses to arrive weekly. At that rate,
considering South Carolina's 70-and-older population is 630,000,
it could take 10 weeks just to vaccinate that age group.
States look for more COVID-19 vaccine doses
Michigan, Wisconsin and Minnesota governors wrote to Human Services
Secretary Alex Azar
"Without additional supply or authorization to purchase directly,
our states may be forced to cancel plans
for public vaccination clinics in the coming weeks,
which are expected to vaccinate tens of thousands.
It's time for the Trump administration
to do the right thing and help us end this pandemic"
Gov. Polis estimated that of the 58,000 remaining doses in Colorado,
"they will likely all or almost all be used by Sunday."
Pfizer tried on Friday to reassure about its vaccine production,
saying it didn't anticipate any shipment interruptions.
[ not anticipating == reassurance?? ]
"Operation Warp Speed has asked us to start shipping second doses only recently.
As a result, we have on hand all the second doses of the previous
shipments to the US.
We are working around the clock to produce millions more each day."
How some states are administering COVID-19 vaccines at twice the speed of others
[employing more competent bureaucracies? nah..]
In the states moving faster, strategic planning and communication,
reliance on strong local partnerships and states taking ownership of
the process have each played a role. North Dakota and West Virginia lead,
having administered more than 65% of distributed doses.
"The biggest thing that we've done is backed away from the (federal)
standardized program," West Virginia Governor Jim Justice told CNN.
By acting independently, West Virginia started vaccinating
in long-term care facilities about a week before other states.
Notably, many states administering their vaccine distributions most efficiently
are among the most rural in the country. Fewer health systems responsible
for larger shares of the population may play a role in success, some say.
On Saturday, India began a coronavirus vaccination program to inoculate
around a quarter of the population, or 300 million people, over coming months,
including healthcare workers, people aged over 50 and those at high risk.
On the first day, around 300,000 people were to be vaccinated at 3,000 centres.
About 150,000 staff in 700 districts have been trained to administer jabs and keep records.
A total of 29,000 cold-chain points, 240 walk-in coolers, 70 walk-in freezers,
45,000 ice-lined refrigerators, 41,000 deep freezers and 300 solar fridges are ready.
https://medicalxpress.com/news/2021-01-india-jumbo-sized-vaccine-rollout.html
I found much less related news today than usual for Saturdays.
This loss of attention will presumably correlate with accelerated infection spread.
USAFacts data updates have become increasingly sporadic;
I originally selected that source, not only because it was among the
first to avoid decreasing cumulative totals, but also because it
organizes a full U.S. case history by county into a 4 megabyte CSV
file, while roughly comparable NY Times data consumes 37 megabytes
and will be considerably more tedious to render for gnuplot.
Sadly, case data only roughly correspond, with NY Times figures 2 to 7% larger..
Saliva could hold clues to how sick you will get from COVID-19
Several new tests look for SARS-CoV-2 in saliva,
and this work finds a striking correlation between high virus levels there and later hospitalization.
If results are confirmed, saliva tests could help doctors prioritize patients
in early stages of the disease for medicines that drive down virus levels.
What to know about new COVID-19 variants
Two strains of the coronavirus that causes COVID-19 called B.1.1.7 and B.1.351
were found in the U.K. and South Africa and are thought to be 30-80% more transmissible.
podcast and transcript: How bad are the new COVID-19 variants, really?
Vineet Menachery, a virologist at the Galveston National Laboratory who studies coronaviruses:
"The quickest answer at this point is: We don't know yet.
Both viruses, the original and this version, are pretty transmissible.
And so if it's two times worse, you may not be able to see the difference."
Worry: "On a scale of one to 10, I'm probably at a three or a four at this point."
Pfizer temporarily reduces European deliveries of vaccine
To meet the new 2 billion dose target, Pfizer is upscaling production
at its plant in Puurs, Belgium, which "presupposes adaptation of facilities
and processes at the factory which requires new quality tests
and approvals from the authorities."
SARS-CoV-2: From entry to autophagy? (13 pages)
SARS-CoV-2 enters cells through endocytosis upon binding to ACE2
and potentially other cell surface receptors, including integrins.
Using bioinformatics, Meszaros et al. predicted the presence of short amino acid sequences,
called short linear motifs (SLiMs), in the cytoplasmic tails of ACE2 and various integrins
that may engage the endocytic and autophagic machinery. Using affinity binding assays,
Kliche et al. not only confirmed that many of these predicted SLiMs
interacted with target peptides in various components of the endocytosis
and autophagy machinery, but also found that these interactions
were regulated by the phosphorylation of SLiM-adjacent amino acids.
Together, these findings have identified a potential link between
autophagy and integrin signaling and could lead to new ways to prevent viral infection.
A nasally introduced peptide prevents COVID-19 symptoms in lab mice
The peptide proved effective in reducing fever, protecting the lungs,
improving heart function and reversing cytokine storm
- the immune system overreacting to an infection
and flooding the bloodstream with inflammatory proteins.
Biden's plan to fix the COVID-19 vaccine rollout, explained
The full proposal
First, the plan has clear goals to address what supply chain experts call the "last mile"
- the path vaccines take from storage to injection in patients -
by making sure there's enough staff, infrastructure, and planning to actually put shots in arms.
Second, it takes steps to ensure that supply chain problems are fixed proactively,
with careful monitoring and use of federal powers when needed to address bottlenecks.
Last, but just as crucially, there's a public education campaign
to ensure that Americans actually want to get vaccinated when it's their turn.
Which Americans can get a vaccine now? Here's a look at the new guidance.
Presumably it is up to governors to decide, as will the question of required documentation.
Some public health departments have web portals in which people can make appointments.
Others hold mass vaccination events and inoculate people on a first-come, first-served basis.
CVS, Walgreens and a number of other chain pharmacies, including some in grocery and big-box stores,
will soon start vaccinating through a partnership with the federal government.
the C.D.C. reported on Wednesday that about 10.3 million people had received an initial dose,
out of 29.4 million doses distributed around the country so far, including 1.1 million doses given
to long-term care residents and staff.
Lessons from the COVID-19 pandemic for advancing computational drug repurposing strategies
This review focuses on the computational methods for drug repurposing;
most of these studies are not considered successful clinically.
Virus-targeting approaches mostly rely on structure-based drug screening methods,
which take the three-dimensional structures of target proteins
to predict affinities or interaction energies of known chemical compounds to the proteins.
An alternative is deep-learning (DL)-based drug screening,
which can analyze orders of magnitude more compounds,
but requires datasets for training. (9 pages)
Cannabis compounds exhibit anti-inflammatory activity in vitro
in COVID-19-related inflammation in lung epithelial cells
and pro-inflammatory activity in macrophages (14 pages)
The increase of macrophage-secreted IL-6 and IL-8 levels
by cannabis-based treatment may potentially lead to
a worsening of the "cytokine storm" identified in severe COVID-19 patients.
https://www.nature.com/articles/s41598-021-81049-2.pdf
The importance of local context in COVID-19 models (3 pages)
Models helped assess likely effects of proposed interventions
and determine 'counterfactuals', that is,
expected epidemic trajectories if an intervention was not implemented.
However, it is important to stress that projection quality depends on
within- and between-country variation in transmission, control and burden.
Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the U.S. (15 pages)
Traced to the southern U.S. in late May, 20C-US is a variant within the B.1.2 lineage.
They predict that 20C-US may already be the dominant variant of SARS-CoV-2 in the U.S..
This variant has thus far only been reported at very low levels in a handful of other countries,
including Mexico, Australia, New Zealand, Singapore, Thailand, Taiwan, Poland and Israel.
The language of a virus
Researchers leveraged an extensive natural language processing (NLP) toolbox
to identify mutations that allow a virus to escape from recognition by neutralizing antibodies.
Anomalous COVID-19 tests
Universities conduct a large proportion of SARS-CoV-2 community surveillance testing.
At the same time, they have shifted focus to SARS-CoV-2 research.
There are now multiple reports of asymptomatic researchers
who worked with or near non-infectious SARS-CoV-2 nucleic acids
and subsequently tested positive during SARS-CoV-2 surveillance screening.
Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein
"Using X-ray crystallography, we built an atomic model of ORF8,
- which is a secreted protein, not bound to the membrane
like the virus's characteristic spike proteins -
and it highlighted two unique regions:
one that is only present in SARS-CoV-2 and its immediate bat ancestor,
and one that is absent from any other coronavirus"
"We, and others in the research community, believe these interfaces are involved in reactions
that somehow make SARS-CoV-2 more pathogenic than the strains it evolved from."
Promising new antibodies against SARS-CoV-2 found
"Nanobodies are antibody fragments that are so simple
that they can be produced by bacteria or yeast, which is less expensive."
These "nanobodies" are smaller than classic antibodies penetrating the tissue better
and can be produced in larger quantities. The researchers also combined the nanobodies
into potentially particularly effective molecules
attacking different parts of the virus simultaneously.
The approach could prevent the pathogen from evading the active agent through mutations.
How a Well-Meaning Health Policy Created California's Coronavirus Nightmare
The health-care system in California is fraying because the state has tried to
run its health system efficiently. The principles are simple: Keep patients out of hospitals,
funnel people to primary-care doctors, and don't build hospitals you don't use.
Why COVID-19 pneumonia lasts longer, causes more damage than typical pneumonia
Researchers identified critical targets to treat severe SARS-CoV-2 pneumonia and lessen its damage.
The targets are the immune cells: macrophages and T cells.
The study suggests macrophages - cells typically charged with protecting the lung -
can be infected by SARS-CoV-2 and can contribute to spreading the infection through the lung.
Northwestern Medicine will test an experimental drug to treat these targets
in COVID-19 pneumonia patients in a clinical trial early in 2021.
Biden will be taking office next week during the nadir of the coronavirus crisis
[ one hopes that it will not get much worse, but there are delays in the best of times
for federal initiatives and funding to trickle down to local levels. ]
1. The new variants are scary.
2. The mass vaccination campaign in the U.S. is off to a terrible start.
3. Things are likely to get worse before they get better
[ hence, not yet REALLY the nadir ]
"Just because you're scheduling an appointment does not guarantee the vaccine"
At the end of each day, Beaufort (including Hilton Head and Coastal Carolina hospitals)
is planning to take all of the email addresses from interested seniors,
put them into a spreadsheet and upload them into a CDC program
called the Vaccine Administration Management System, or VAMS.
The CDC will then email residents a link to access VAMS
so they can register and choose where they want to get a shot and when.
VAMS lists available appointments.
The National Association of Chain Drug Stores says its members can "easily" meet
President-elect Joe Biden's goal of administering
100 million coronavirus vaccines in the first 100 days of his administration.
The association estimated that each of 40,000 chain pharmacies would have to give
7 shots per hour over a 12-hour day to meet the Biden goal. But the group says
drug stores using several employees to provide shots would actually exceed that estimate.
Arizona reported a record-high 5,082 hospitalized COVID-19 patients Tuesday
and on the same day broke a second record:
more than 1,180 patients with the virus in ICU beds.
Infections increased over a week by an average of 50% in 26 of the 30 U.S. counties
in which full-time enrollment at higher education institutes
accounts for more than a quarter of the population.
Johnson & Johnson Expects Vaccine Results Soon but Lags in Production
Vaccine trial results are expected in as little as two weeks, but the company
has fallen as much as 2 months behind the original production schedule
and won't catch up until the end of April. "We are not ready to release the numbers
month by month at the moment, as we are in the discussion with the F.D.A."
The dirty life and times of SARS-CoV-2
1) It took COVID-19 for scientists to finally question ethics of placebo controlled studies.
2) saying that it is possible that a virus got out of a lab is actually not a conspiracy theory;
it is simply a theory (and thus far as plausible as any proposed zoonotic source).
Why remdesivir does not fully stop the coronavirus
German researchers have now elucidated how remdesivir interferes with the
viral polymerase during copying and why it does fully not block RNA production.
"MDA-5 recognizes replicating viruses in lung cells and activates interferon,
the body's own frontline defender against viral invasion. Without a proper interferon response,
viral infections can lead to deadly, out-of-control inflammatory reactions."
MDA-5 detects double-stranded viral RNA
- a form that SARS-CoV-2 takes when it replicates to spread the infection.
Why Aren't We Wearing Better Masks?
It's past time for better solutions to be available to the public.
Taiwan massively scaled up its manufacturing of masks at the start of 2020,
such that by April every citizen received a fresh supply of high-quality masks each week.
Of thousands of RBD mutations tested, only a few reduced antibodies'
ability to bind tightly to the spike protein,
but effects varied substantially among people.
The most consequential mutations, at a location called E484,
caused a steep drop in the potency of some individuals' antibodies.
Coronavirus variants identified in South Africa and Brazil carry a mutation at the same spot.
https://www.nature.com/articles/d41586-020-00502-w
Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load
persisted for up to 21 days on experimentally inoculated PPE,
including materials from filtering facepiece respirators (N-95 and N-100 masks)
and a plastic visor. Conversely, when applied to 100% cotton fabric,
the virus underwent rapid degradation and became undetectable by TCID50 assay within 24 h.
https://www.nature.com/articles/s41598-020-80098-3
The feasibility of targeted test-trace-isolate for the control of B.1.1.7
Their model indicates that bidirectional contact tracing can substantially slow the spread
of B.1.1.7 even in regions where a large fraction of the population refuses to cooperate
with contact tracers or to abide by quarantine and isolation requests.
Americans have unrealistic expectations for a COVID-19 vaccine
[ full stop after "expectations" also works ]
Americans are most likely to intend to vaccinate when a vaccine is made in the U.S.,
administered in a single dose, over 90% effective and carrying a less than 1 in 100 chance
of experiencing minor side effects, and has spent just over a year in development.
Even under these ideal conditions,
the likelihood that the average respondent would choose to vaccinate is just 68%.
U.S. ramps up vaccinations to get doses to more Americans
After a frustratingly slow rollout involving primarily health care workers and nursing home residents,
states are moving on to the next phase before the first one is complete,
making shots available to such groups as senior citizens, teachers, bus drivers, police officers and firefighters.
States and hospitals: overhaul your vaccine plans with data before it's too late
Supposed to deliver shots to 24 million health care workers and long-term care residents,
the vaccine rollout first phase has been stymied by poorly conceived distribution plans based on judgement calls.
Without better use of sound science and data, vaccine plans for the next two phases,
which aim to inoculate nearly 180 million Americans, could descend into chaos.
Mitochondria may be one of the first lines of defense against COVID-19
SARS-CoV-2 uniquely reduces levels of a group of mitochondrial proteins, Complex One,
that are encoded by nuclear DNA. It is possible that this effect
"quiets" the cell's metabolic output and reactive oxygen species generation
that when functioning correctly, produces an inflammatory response that can kill a virus.
Study links severe COVID-19 disease to short telomeres
The study, led by Maria A. Blasco with first authors are Raul Sanchez and Ana Guio-Carrion,
postulates that telomere shortening as a consequence of the viral infection
impedes tissue regeneration and that this is why
a significant number of patients suffer prolonged sequelae.
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections (16 pages)
Two groups of mouse neutralizing monoclonal antibodies (MAbs), 2H2 and 3C1,
bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail.
A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection
in vitro with half inhibitory concentration (IC50) of 12 ng/mL
and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection.
Early warning system fills in gaps in infectious disease surveillance
The approach compensates for existing gaps by optimally assigning surveillance sites
that support better observation and prediction of the spread of an outbreak,
including to areas remaining without surveillance.
"Our method can be used to support development of a more robust surveillance system
and to identify where to set up or improve surveillance."
Accurate COVID-19 prevalence measurement in the field (20 pages)
Since virus testing is voluntary, all tests done in the field, even if supposedly random,
suffer from selection bias; volunteers are up to 38 times more likely to suspect they are infected.
This paper suggests ways to correct the bias of the testing stations, but even better,
a cleaner way to sample the population to avoid the bias altogether.
More SC health care workers refused or deferred COVID-19 vaccine than expected
As of Friday, just under 71,000 of the 350,000 South Carolinians front
line health care workers who fall into SC's Phase 1a had received a
first dose of vaccine, according to DHEC.
SC ranks 47th among states in its vaccine administration rate.
Public health officials sounded the alarm for months,
complaining that they did not have enough support or money to get COVID-19 vaccines
quickly into arms. Now the slower-than-expected start to the largest
vaccination effort in U.S. history is proving them right.
Deep learning-based detection of COVID-19 using wearables (Fitbit) data (29 pages)
Abnormal resting heart rate was detected during the period of viral
infection (7 days before the symptom onset and 21 days after) in 92%
(23 out of 25 cases) of patients with laboratory-confirmed COVID-19.
In 14 cases, LAAD detection identified cases in their pre-symptomatic
phase whereas 9 cases were detected after the onset of symptoms.
Efficacy of propolis as an adjunct treatment for hospitalized COVID-19 patients:
a randomized, controlled clinical trial (21 pages)
Propolis is produced by honey bees from bioactive plant exudates.
Patients received standard care plus propolis at an oral dose of
400mg/day (n=40) or 800mg/day (n=42) for seven days, or standard care alone (n=42).
Time in the hospital after intervention was significantly shortened in
both propolis groups compared to the controls; median 7 days with 400mg/day
and 6 days with 800mg/day, versus 12 days for standard care alone.
L.A. County hospitals prepare for triage care rationing as COVID-19 cases overwhelm
The new guidelines were first reported by the Los Angeles Times
as Los Angeles County hospitals treat more than 8,000 COVID-19 patients,
a growing number that has shown no sign of slowing down
as the region continues to report thousands of new cases each day.
On Friday, just 54 adult ICU beds were available in the county of 10 million residents,
but the most likely shortage will be of staff, for example
with a shortage of respiratory therapists
leaving triage officers to determine patients' ventilator management.
We lost to SARS-CoV-2 in 2020. We can defeat B-117 in 2021
Because B-117 can grow exponentially even in communities that are keeping SARS-CoV-2 under control,
the situation is extremely urgent. Thermo Fisher makes TaqPath test kits capable of detecting B-117,
which exhibits a pattern of "S-gene dropout" distinguishing it from SARS-CoV-2.
As soon as the first person is diagnosed with B-117 in a community,
local contact tracers should drop everything else in order to map
the complete chain of transmission of the new strain using every resource available.
B117 coronavirus variant found in eight U.S. states
California, Florida, Colorado, Texas, New York, Georgia, Connecticut and Pennsylvania
Fauci told Newsweek on Wednesday that the variant may be
"more widespread in the U.S. than we are currently detecting it to be".
The Next Phase of Vaccination Will Be Even Harder
Getting vaccines to hospitals and nursing homes was supposed to be the easy part.
In coming months, state and local health departments are supposed to set up mass-vaccination clinics
that can handle hundreds or even thousands of people a day in the middle of a pandemic, when crowds are dangerous.
Thousands of doctors' offices and pharmacies across the country
will also need to learn how to handle and administer unusually fragile vaccines.
How Badly Is Vaccination Going?
Interview transcript: Juliette Kayyem, a former assistant secretary of homeland security
"when I look to the end of January and early February,
I think we can't quite grasp how game-changing, if it works,
the Johnson & Johnson vaccine will be. Because that's an old-school vaccine:
single dose, no cold storage necessity. You'll start to see this look a bit like the flu vaccine,
where we can walk into CVS and Walgreens."
AXL is a candidate receptor for SARS-CoV-2
that promotes infection of pulmonary and bronchial epithelial cells (15 pages)
Although the role of ACE2 as a receptor for SARS-CoV-2 is clear,
studies have shown that ACE2 expression is extremely low in various human tissues,
especially in the respiratory tract.
Overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry
as efficiently as does overexpression of ACE2,
while knocking out AXL significantly reduces SARS-CoV-2 infection
in H1299 pulmonary cells and in human primary lung epithelial cells.
Vimentin binds to SARS-CoV-2 spike protein
and antibodies targeting extracellular vimentin
block in vitro uptake of SARS-CoV-2 virus-like particles (30 pages)
Not all ACE2-expressing cells are equally infected,
suggesting that other extracellular factors are involved in host cell invasion by SARS-CoV-2
Results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection,
focusing on targeting cell host surface vimentin.
https://www.biorxiv.org/content/10.1101/2021.01.08.425793v1.full.pdf<>/a>
Pfizer/BioNTech vaccine appears effective against coronavirus variants
The not-yet peer reviewed study by Pfizer and scientists from the University of Texas Medical Branch
indicated the vaccine was effective in neutralizing virus with the so-called N501Y mutation of the spike protein.
"So we've now tested 16 different mutations,
and none of them have really had any significant impact."
Another mutation found in the South African variant, called the E484K mutation, is also concerning.
[ While numerous sources assert that these mRNA vaccines can be
"tweaked to address new mutations" in as little as 6 weeks,
'tweaked' vaccines would presumably need at least 3 months of trials to get EUAs. ]
(16 pages)
Sensitivity with self-testing was 82.5% and 85.0% with professional testing.
Optimal design for phase 2 studies of SARS-CoV-2 antiviral drugs (13 pages)
Rate of viral clearance is a uniformly superior endpoint as compared to time to clearance.
Pharmacometric assessments should be conducted in early illness
and daily qPCR samples should be taken over 7 to 10 days in each patient studied.
Adaptive randomisation and early stopping for success permits more rapid identification of active interventions.
Ultrasensitive RNA biosensors for SARS-CoV-2 detection
in a simple color and luminescence assay (23 pages)
Optimizing RNA-amplification and biosensor-design generated a highly-sensitive diagnostic assay;
with sensitivity down to attomolar (100 copies of) SARS-CoV-2 RNA,
in 100 minutes, correlating well with Ct values from RT-qPCR tests.
A smartphone-read ultrasensitive and quantitative saliva test for COVID-19 (12 pages)
Portable COVID-19 assay with 15-min sample-to-answer time that requires neither RNA isolation
nor laboratory equipment but robustly quantified viral load over a broad linear range (1 to 105 copies/ul)
and exhibited a limit of detection (0.38 copies/ul) below that of the RT-PCR reference assay.
This saliva assay exhibited complete concordance with RT-qPCR results from paired nasopharyngeal samples,
a low limit of detection, and a broad linear range,
and thus appears suitable for ultrasensitive point-of-care COVID-19 screening efforts.
https://advances.sciencemag.org/content/7/2/eabe3703/tab-pdf<>/a>
Why we need to test COVID-19 tests
A highly sensitive test will reduce false positive results in a low prevalence setting;
high specificity avoids unnecessary treatments there.
CDC foresees spread in U.S. of highly contagious coronavirus variant
[ arguably no longer COVID-19]
The rise of variants also could limit the efficacy of monoclonal antibody treatments
because such therapeutics are very narrowly focused
and potentially could be eluded by a single mutation.
More U.S. Pharmacies to Start Vaccinating High-Risk Groups
In Louisiana, about 100 pharmacies across the state this week will start to give doses
of the Moderna vaccine to people over 70, health care workers, and patients on dialysis.
In Florida, seniors will be able to start making appointments on Thursday
to get the Moderna vaccine at 22 Publix Supermarkets pharmacy locations across the state.
A federal program to give out vaccines at pharmacy stores to high-risk groups,
including older people and frontline workers, being activated this week,
was announced in November without a time table for its launch.
Early High-Titer Plasma Therapy to Prevent Severe COVID-19 in Older Adults
A total of 160 patients underwent randomization. In the intention-to-treat population,
severe respiratory disease developed in 13 of 80 patients (16%)
who received convalescent plasma and 25 of 80 patients (31%) who received placebo.
Japan Issues COVID-19 State Of Emergency For Tokyo As Infections Rise
The emergency will take effect Friday and last until Feb. 7.
While case numbers are low by Western standards, their rapid increase has alarmed Japan.
Thursday's tally of 6,100 cases set a record, with Tokyo making up about half.
Along with vaccine rollouts, the U.S. needs a National Hi-Fi Mask Initiative
While most masks provide some level of protection for the wearers and those around them, many masks,
including the widely used cloth and surgical masks,
only partially filter the small COVID-19-spreading aerosols that people emit when coughing,
sneezing, breathing, and talking. As demonstrated in a recent study,
high-filtration (hi-fi) masks like N95 masks are the best protection against these small particles.
CDC model finds asymptomatics spread virus in more than half of cases
"These are pretty believable, solid results."
The model consistently predicted asymptomatic spread accounted for roughly half of viral transmission.
"I was a bit surprised how well it held up under a broad range of base assumptions"
'Human disaster' unfolding in LA will worsen
Ambulance crews told not to take patients with little chance of survival to hospitals.
Ambulances wait for hours outside hospitals. "There are situations
where patients are made to wait in ambulances under the care of the paramedics."
U.S. speeds plan for pharmacies to give COVID-19 shots
As of Tuesday morning, more than 70% of the more than 17 million
vaccine doses that have been delivered around the U.S. since December
were still sitting in freezers
Some SARS-CoV-2 transmission occurs after 7 or 10 days
76 and 86 % of test results were positive within 7 and 10 days, respectively,
after an index patient's illness onset date. The chance of remaining asymptomatic
and receiving negative test results through day 14 was 81 and 93%, respectively.
Ivermectin shows clinical benefits in mild to moderate COVID-19 (31 pages)
12 mg IV regime may have better efficacy than 6 mg.
IV should be considered for clinical management of SARS-Cov-2,
and may find applications in community prophylaxis in high-risk areas.
Immunological memory to SARS-CoV-2 assessed
for up to 8 months after infection (23 pages)
IgG to the Spike protein was relatively stable over 6+ months.
Spike-specific memory B cells were more abundant at 6 months
than at 1 month post symptom onset. SARS-CoV-2-specific
CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months.
Geographic monitoring for early COVID-19 cluster detection (11 pages)
GeoMEDD has proven effective in revealing different types of clusters,
as well as influencers and accelerators that give insight
as to why a cluster exists where it does, and why it evolves.
llumina, Inc., and Helix announced collaboration on sequencing technology, expertise,
and a national testing footprint to significantly expand U.S. SARS-CoV-2 surveillance efforts
for detecting and characterizing emerging variants.
vaccines "might not" work as well on South African COVID-19 strain, 501.V2
The lead researcher on the trial of the Oxford vaccine carried out in South Africa,
Professor Shabir Madhi, said Monday that more than 13 variants of the coronavirus
had been identified in the country since the start of the pandemic.
He said the new one, 501.V2, which has spread like wildfire in South Africa's coastal cities,
is the most worrying mutation of the virus so far.
"It's not a given that the vaccine will not work on this variant,
but it is a consideration that the vaccine might not have the full efficacy."
Covaxin: Concern over 'rushed' approval for India COVID jab
Health watchdog All India Drug Action Network said that there were
"intense concerns arising from the absence of the efficacy data"
as well a lack of transparency that would "raise more questions than answers
and likely will not reinforce faith in our scientific decision making bodies"
Cold sensitivity of the SARS-CoV-2 spike ectodomain (11 pages)
To obtain consistent results in serology assays or other binding studies
using the so-called '2P' S ectodomain or similar constructs,account for demonstrated cold sensitivity.
Estimating and explaining the spread of COVID-19 at the county level in the USA (9 pages)
Most of the high among-county variance is explained by four factors:
the timing of outbreak, population size, population density, and spatial location.
For predictions of future spread, population density and spatial location are important,
and, for the latter, SARS-CoV-2 strains containing the G614 mutation to the spike gene
are associated with higher rates of spread.
Crossreactivity not so helpful after all?
Crossreactive CD4+ T cells can be detected in almost all individuals tested,
and these cells generally have a low functional avidity. However,
highly expanded populations of low-avidity CD4+ T cells are a hallmark of severe COVID-19.
This challenges the idea of a protective function for crossreactive CD4+ T cells
and even raises the possibility that these cells may increase severe symptom risk.
Deciphering the protective features of the antibody response
Overall, outpatients and asymptomatic individuals had
higher ratios of spike protein receptor-binding domain-specific IgG
versus nucleoprotein-targeted IgG antibodies than hospitalized patients.
In hospitalized patients, antibody titres inversely correlated with viral titres,
but antibody responses during acute illness were insufficient to predict outcomes.
In all patients, antibody titres started to wane around 1 month after disease onset.
Georgia is experiencing its "worst surge" of COVID-19 ahead of the Senate runoffs
Georgia ranks 10th among the states in new cases per 100,000 people,
ninth in positive test rate, and second in filled ICU beds (now up to 92%).
More than 40 Georgia hospitals are on "diversion," meaning they are
not accepting any patients for any reason into their emergency room or ICU units.
Gov. Brian Kemp has never issued a mask mandate. Indoor dining is permitted.
Spike protein disulfide disruption as a potential treatment for SARS-CoV-2 (38 pages)
Reagents capable of reducing disulfide bonds can inhibit viral infection in cell-based assays.
Addition of exogenous disulfide bond reducing agents affects the RBD secondary structure,
lowers its melting temperature from 52 to 36-39 degrees Celsius
and decreases its binding affinity to ACE2 by two orders of magnitude at 37C.
absurd or moronic? also: Azithromycin and Zinc - get a script
[ trick question, to which the answer is: both ]
1) "For us to reach 80% herd immunity through vaccination,
it will take us 10 years at a rate of 1 million vaccines a week,"
Dr. Leana Wen, former Baltimore health commissioner.
[ With absolutely no data suggesting vaccine immunity beyond 6-8 months,
herd immunity is doomed unless/until enough are vaccinated within that time ]
2)
FDA considering cutting Moderna vaccine doses in half to speed up roll out
[ Having empirically demonstrated that getting shots in arms, not supply,
is THE bottleneck, why not also deliberately compromise their effectiveness?
Reduced dosage immunity duration reduction could lose immunity
before getting access to subsequent shots.
I suspect that weak immunity provokes more severe subsequent infections. ]
Johnson & Johnson's single-dose vaccine next to seek emergency use authorization
Its adenovirus-based Janssen vaccine does not require ultra-cold storage,
using the same technology developed for Ebola vaccine.
Phase 3 safety and efficacy are expected to be released by the end of January.
Johnson & Johnson plans to manufacture more than a billion doses globally in 2021.
COVID variant in South Africa is 'more of a problem' than U.K.'s
"They both have multiple, different mutations in them, so they're not a single mutation.
And the mutations associated with the South African form
are really pretty substantial changes in the structure of the (virus' spike) protein."
For its part, the U.K. has banned visitors from South Africa.
Japan poised for a state of emergency as COVID-19 cases soar,
a number of which have been linked to a new, potentially more infectious variant.
Japan was one of the first countries hit by the pandemic, but the government
had been able to keep cases at bay by enacting stringent border controls,
investing efforts in contact tracing and pushing citizens to practice social distancing.
Japanese authorities are currently limited in their powers to punish those who
breach restrictions, even in a state of emergency, something Suga's government
is reportedly planning to change to enable local governments to force compliance.
New Prime Minister Yoshihide Suga dismissed calls to declare a state of emergency
in November, citing advisory panel advice that hospitals were still relatively empty.
Japan ranks "among the countries with the lowest vaccine confidence in the world"
The virus is still winning
Cases have surged in Britain and South Africa since their variants first surfaced
- while holding fairly steady in the rest of western Europe and southern Africa.
Cuomo threatens to fine hospitals if they don't step up vaccination pace.
194 NY hospitals have received about 46% of the state's total vaccine allocation,
he said at a briefing Monday.
"I need those public officials to step in and manage those systems.
You have the allocation; we want it in people's arms as soon as possible."
Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients (15 pages)
A retrospective study of 115 COVID-19 hospitalized patients
using high-throughput data analysis of 118 clinical parameters for all.
High anti-DNA antibodies showi a positive predictive value of 89.5%
and accounted for 22% of total severe cases. [AKA sufficient, but not necessary]
Insights into the molecular mechanism of anticancer drug ruxolitinib
repurposable in COVID-19 therapy (16 pages)
Ruxolitinib treatment elicited response equivalent to that of SARS-CoV-2 uninfected situation
by inducing defense response in host against virus infection by RLR and NOD like receptor pathways.
Further, the effect of ruxolitinib in SARS-CoV-2 infection was mainly caused
by significant suppression of IFIH1, IRF7 and MX1 genes as well as
inhibition of DDX58/IFIH1-mediated induction of interferon- I and -II signalling.
Evaluation of 3 rapid lateral flow antigen detection tests for SARS-CoV-2 (15 pages)
Sofia (Quidel), Standard Q (SD Biosensor), and Panbio (Abbott)
Specificity of all 3 was 100%; sensitivity and agreement was 80% and 85% for Sofia,
81% and 85% for Standard Q, and 83% and 86% for Panbio, respectively.
Can early home treatment with Azithromycin alone or with Zinc
help prevent hospitalisation, death, and long-COVID-19? (20 pages)
a scoping review of articles published from 31 December 2019 to 5 November 2020
The antiviral, anti-inflammatory, immunomodulatory benefits of AZM + Zn
make this drugs combination a good candidate therapy
to treat flu-like-COVID-19 and atypical pneumoniae.
Early use of this therapy by family practitioners
for home treatment of individuals presenting mild or moderate symptoms is called for.
Long COVID: who is at risk?
13% who experience COVID-19 symptoms have them for more than 28 days,
while 4% have symptoms after more than 56 days. More severe disease,
older age and being female also appear to be risk factors for prolonged symptoms,
as is having a higher body mass index.
Q&A with Helen Branswell, one year after COVID-19 became a full-time job
"It never occurred to me - and I'm sure I'm not alone in this -
that the U.S. would handle a pandemic worse than almost any other country,
and definitely worse than peer countries. The U.S. spent a lot of time
and buckets of money on pandemic preparedness in the mid-aughts,
but you wouldn't know it from the country's response to the COVID pandemic."
Statehouses could prove to be hothouses for virus infection
As lawmakers around the U.S. convene this winter to deal with crises created by the pandemic,
statehouses themselves could prove to be hothouses for infection.
More than 250 state lawmakers across the country have contracted COVID-19.
need to again resize/rescale; Missouri remains broken:
Record 134 new cases Thursday in Beaufort County SC
The previous single-day high in Beaufort County was 113 new cases on July 30.
South Carolina reported a record 3,648 new infections statewide on New Year's Day.
U.S. COVID-19 hospitalizations have exceeded 100K for 32 days.
"This is about total collapse of the health care system if we have another spike"
New York added almost 16,500 new cases on Friday,
a day after hitting its highest ever one-day case count,
becoming the 4th state to surpass 1 million cumulative official cases.
Texas health officials reported record-high COVID-19 hospitalizations
across the state for the fifth day in a row, with more than 12,400 patients
and a cumulative state total of 1.7 million cases.
CA has 2.3 million, and Florida has 1.3 million.
4.2 of 13 million vaccines doses have been administered in the U.S..
America's Vaccine Rollout Is Already a Disaster
The U.S. has 40 million doses and administered only 2 million of those.
In 1947, New York City vaccinated 5 million people against smallpox in two weeks.
Rushing to get as many first doses as possible out, and waiting for new supply
to deliver second doses, could avert as many as 34 to 42 percent of new infections.
Vaccines are only cleared for 30 days of storage in the most common units
(including those in which they have been shipped).
L.A. County doctor beset by intensely sick COVID-19 patients
"It's not the volume of patients. It's the intensity and sickness of the patients.
I've never thought some of these numbers are compatible with life,
with patients coming in sicker than you can imagine."
Arizona starts the new year with a 2-day high of COVID-19 cases
Arizona had the second-worst COVID-19 diagnosis rate over the past week, behind only California.
Hospital officials have said the crush of COVID-19 patients may force imposition of triage protocols
that the state could order to help hospitals decide how to decide which patients get access to limited resources.
Today, every state except Hawaii exceeds 12 new cases per 100,000 daily.
Some is due to greater testing, but climbing hospitalizations and deaths,
which have reached record highs nationally in the last month,
show this is not merely a "casedemic" of sick people
who might have gone undetected earlier in the year.
Nearly a year into the pandemic, no state has capacities for testing
and contact tracing that most experts would consider adequate.
Fast-spreading U.K. virus variant raises alarms
Fairly easy to read.
The U.K.'s new COVID-19 lockdown and other countries' border closures
mark the first time such drastic action has been taken
based on genomic surveillance in combination with epidemiological data.
Experiments are under way to evaluate whether current vaccines remain effective
"New" COVID-19 variant may have been in U.S. since October
In the final hours of 31 December, Florida reported a case of the variant.
California-based DNA testing company Helix examined S gene dropout
prevalence among 2 million COVID tests processed in recent months.
S gene dropout increased among positive samples since early October,
when 0.25% of positive tests exhibited this pattern,
to about 0.5% this week.
West Virginia clinic gave 44 people an antibody treatment
instead of the coronavirus vaccine
[ It could happen to any illiterate ]
Regeneron's REGEN-COV2 is intended to be infused,
NOT given as an intramuscular shot, so a twofer.
"It has been determined that this was an isolated incident,"
Julie Miller, an administrator for the Boone County Health Department
Should placebo vaccine volunteers now get the real thing?
"There's a real tension here," said Dr. Jesse Goodman, an infectious
disease specialist and former chief scientist at the U.S. Food and
Drug Administration. "There's not an easy answer." Quack, quack.
[ Actually, there IS an easy answer: Jesse Goodman is an idiot.
Any statistician who cannot recalculate candidate vaccine efficacy
lifetime, comparing statistics for volunteers who received the
candidate to placebo subjects now receiving a different vaccine of
known efficacy should be fired.
Yes, that is a different result, but also more valuable,
except perhaps for the vaccine maker. ]
Microvascular Injury in the Brains of COVID-19 Patients
Abnormalities were seen in the brains of 10 of 13 patients MRI-ed.
Magnetic resonance microscopy showed punctate hyperintensities in 9 patients,
which represented areas of microvascular injury and fibrinogen leakage.
Emergence of a Highly Fit SARS-CoV-2 Variant
This article is about the D614G-associated SARS-CoV-2, discovered in February
that evolved in southern Europe and then flew to NYC. It outcompetes with the
original D614 strain by being more stable and replicating to higher titers in
upper respiratory samples, but as sensitive to neutralization as the ancestral strain.
With limited surveillance of COVID-19 variant, it's deja vu all over again
There are 250 genetic sequences of SARS-2 viruses from December U.S. cases
that have been logged into an international virus sharing database
known as GISAID; there isn't a B.1.1.7 (the UK variant) among them.
The U.S. does too little SARS-CoV-2 sequencing to detect it.
"I do think that wastewater is going to be the best way in the very near term
to get a better handle rather than waiting for the odd lab like Colorado
that comes across one of these in an individual patient sample"
The CDC is "scaling up" to handle 750 samples a week.
[UK sequences 5-10% of all positive tests...]
Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways
upon exposure to cough-generated droplets and aerosol particles (8 pages)
The probability of direct infection of acinar airways due to inhalation of particles emitted by a bystander cough is very low.
As the number of viruses deposited in extrathoracic airways is about 7 times higher than in acinar airways,
most COVID-19 pneumonia cases must be preceded by infection of upper airways.
Even non-specific treatment forms like disinfection of throat, nasal and oral mucosa
may effectively keep upper airway viral loads low enough to avoid or prolong disease progression.
A model to rate strategies for managing disease due to COVID-19 infection (10 pages)
A mathematical model describing viral infection dynamics
reveals two transmissibility parameters influenced by management strategies for pandemic control.
Both parameters readily yield a peak infection rate and means for curve flattening,
which is correlated to different management strategies by employing machine learning,
enabling comparison of different strategies and suggesting timely alterations.
Given recent evidence of SARS-CoV-2 transmission by mildly symptomatic and asymptomatic persons,
its incubation period is about 5.1 days
and about 12 days of infection from exposure to symptom development (latent period).
Flattening the curve worked - until it didn't
The U.S. failed to take advantage of that window
to ramp up testing-and-tracing capabilities and improve mask effectiveness.
States quickly relaxed their policies to appease populists, ignoring science.
Staff to staff transmission as a driver of healthcare worker infections with COVID-19
Of 45 staff who returned a positive test result for SARS-CoV-2,
19 were determined to be acquired at Austin Health.
15/19 of these were identified through contact tracing
and testing following exposures to other infected staff
and were presumed to be staff-staff transmission. (22 pages)
[Alternatively, they may have been from an undetected non-staff superspreader]
The Pandemic Surges in the West, South, and Northeast
hotspots are primarily in the Sun Belt, including
California, Nevada, Mississippi, Alabama, Tennessee, and Georgia
CA, Az, FL, TX, TN account for 40% of new cases Dec 17-23
Just behind Nevada and Arizona in hospitalizations per million is Alabama.
Hydrogel particles improve detection of SARS-CoV-2 RNA
from multiple sample types (11 pages)
The method concentrates virus from 1 mL samples prior to RNA extraction,
substantially improving detection of virus using real-time RT-PCR,
allowing a sample processing time of 10 min,
substantially improved detection of the virus in low viral load samples.
Rapid and complete inactivation of SARS-CoV-2 by ultraviolet-C irradiation
Using commercially available Signify ultraviolet (UV)-C light source at 254 nm
on both wet and dried droplets.(5 pages)
https://www.nature.com/articles/s41598-020-79600-8.pdf
Fluid dynamics of COVID-19 airborne infection
suggests urgent data for a scientific design of social distancing (9 pages)
Different initial distributions of droplet size taken from literature and
different ambient relative humidity lead to opposite conclusions:
(1) most versus none of the viral content settles in the first 1-2 m;
(2) viruses are carried entirely on dry nuclei versus on liquid droplets;
(3) small droplets travel less than 2.5 m versus more than 7.5 m
Results here are obtained in the absence of external airfows.
Relative humidity has a particularly dramatic effect,
with all droplets evaporating to their dry nuclei under sufficiently dry conditions
and all droplets remaining liquid under sufficiently wet environmental conditions
State-specific projection of COVID-19 infection in the U.S.
and evaluation of three major control measures (9 pages)
A travel-network-based susceptible-exposed-infectious-removed (SEIR)
mathematical compartmental model system that characterizes infections
by state and incorporates inflows and outflows of interstate travelers.
Modeling reveals that curbing interstate travel when the disease is already widespread will make little difference.
Meanwhile, increased testing capacity (facilitating early identification of infected people and quick isolation)
and strict social-distancing and self-quarantine rules are most effective in abating the outbreak.
The modeling has also produced state-specific information. For example, for New York and Michigan,
isolation of persons exposed to the virus needs to be imposed within 2 days to prevent a broad outbreak,
whereas for other states this period can be 3.6 days.
LinearSampling: Linear-Time Stochastic Sampling of RNA Secondary Structure
with Applications to SARS-CoV-2 (15 pages)
Orders of magnitude faster than the standard stochastic algorithm
for sampling RNA structures, LinearSampling is claimed to be
the first sampling algorithm to scale to the full genome of SARS-CoV-2,
taking only 96 seconds on its reference sequence (29,903 nt).
It finds 23 regions of 15 nt with high accessibilities,
which can be potentially used for COVID-19 diagnostics and drug design.
tracking who has received first dose of which vaccine
Nursing homes have largely had to create their own plans to keep track
of people who have received a first dose receiving little guidance
from state or federal health officials in a process
that is already turning into a logistical mess.
Novavax launches U.S. phase 3 trial of COVID-19 vaccine after manufacturing delays
Novavax's COVID-19 candidate is one of two protein subunit vaccines.
Its lipids lack polyethylene glycol that has provoked allergic
reactions in other vaccines, but it is supplemented by an
immune-boosting saponin compound.
108 U.S trial sites and seven in Mexico are recruiting 30,000 volunteers.
WHO: COVID-19 Pandemic 'Not Necessarily the Big One'
"This virus is very transmissible... and it kills people
and it has deprived so many people of loved ones.
But its current case fatality is reasonably low
in comparison to other emerging diseases. This is a wake-up call."
UK model used to evaluate lockdowns was flawed
"an almost total lack of systematic review of the sensitivity
of different models in terms of parameters and data."
Since most measures were introduced at roughly the same time over a
few weeks in March, data lack information to differentiate their
individual effects.
An explanation for COVID-19 "happy hypoxia" (3 pages)
patients do not report feeling shortness of breath or increased breathing rates,
despite low blood oxygen.
Experiments have revealed a high presence of the enzyme ECA2,
the protein the coronavirus uses to infect human cells, in the carotid body,
which could alter its ability to detect blood oxygen levels.
Where the Pandemic Will Take America in 2021
In December, a daily average of 2,379 Americans have died of COVID-19
- comparable to 2,403 who died in Pearl Harbor and 2,977 who died on 9/11.
Many of the 30 epidemiologists, physicians, immunologists,
sociologists, and historians interviewed for this piece are cautiously
optimistic that the U.S. is headed for a better summer. Its
realization hinges on successfully executing the most complicated
vaccination program in U.S. history.
One certainty about the vaccines is that they will be deployed unevenly.
Drugs that block HIV infections have been around for years,
but 1.7 million people still contract the virus every year.
In-depth blood proteome profiling analysis revealed distinct
functional characteristics of plasma proteins between severe and
non-severe COVID-19 patients (10 pages)
Quantitative proteomic analysis using the BoxCar method revealed that
91 out of 1222 quantified proteins were differentially expressed
depending on the severity of COVID-19. Importantly, 76 proteins,
previously not reported,
could be novel prognostic biomarker candidates.
https://www.nature.com/articles/s41598-020-80120-8.pdf
Which COVID policies are most effective?
A Bayesian analysis of COVID-19 by jurisdiction (19 pages)
The study used a model to generate estimates of the marginal impact of
11 categories of COVID-19 control policies were examined including
school closings, workplace closings, cancellation of public events,
restrictions on gatherings, closing of public transport, stay-at-home
requirements, restrictions on internal movement, international travel
controls, public information campaigns, testing, and contact tracing.
In most jurisdictions examined,
policies with a lesser social impact including cancellation of public
events, restrictions of gatherings to fewer than 100 people, and
recommendations to stay at home, are not enough in themselves to
control COVID-19.
Socially intolerable measures such as stay-at-home orders,
targeted or full workplace and school closings are also required.
Rapid inactivation in vitro of SARS-CoV-2 in saliva by black tea and green tea (15 pages)
Black and green tea decreased virus titer to less than 1/100 within 10 sec
SPINT2 controls SARS-CoV-2 viral infection
and is associated to disease severity (27 pages)
SPINT2 is a member of the family of Kunitz type serine protease inhibitors
and has been shown to inhibit TMPRSS2. SPINT2 negatively correlates
with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines
and was down-regulated in secretory cells from COVID-19 patients.
Losartan promotes cell survival following SARS-CoV-2 infection (24 pages)
Angiotensin II type I receptor blocker, Losartan, may reduce the affinity
of the virus for ACE2, and inhibit papain-like protease of the virus.
Losartan treatment of Vero E6 cells prior to and after SARS-CoV-2
infection reduced SARS-CoV-2 replication by 80% and 70% respectively.
Frustration over vaccine rollout builds,
as new variant reported in U.S. for first time
The Colorado case contracted the virus in the U.S.,
suggesting undetected transmission of the new variant here.
"No effort from Feds to help states launch a real vaccination infrastructure."
Tracking the vaccine, state by state
Although Feds plan to distribute second doses in early January, at least some
states withheld distributing roughly half of their received vaccines
to use as second doses. AKA SNAFU.
COVID-19 January projections are 'nightmarish'
"We very well might see a post-seasonal - in the sense of Christmas, New Years - surge,"
Dr. Anthony Fauci said on CNN's "State of the Union" Sunday morning, pointing to
holiday travel and private gatherings taking place despite the advice of health experts.
Healthcare workers make up the largest group among South Carolinians
who have tested positive for the virus so far
and whose occupations state health officials have recorded. (nearly 1 in 4)
COVID-19 overwhelms Los Angeles County hospitals
The entire lobby of the Martin Luther King Jr. Community Hospital
has been converted into space to treat patients,
gurneys have been placed in gift shop, and the waiting room is a tent outside.
"I live in South Carolina, and in the upstate area [where I live],
we shut down for maybe two weeks max. It was so quiet and weird.
But what was really weird was that very shortly after that, everything was back to normal.
Everybody was out, like the pandemic didn't exist. No one was wearing masks.
The times when I'm in the building, loading my packages in my truck, I have my mask on.
Some of my coworkers do, but most of them absolutely do not wear their masks.
And it's so stressful to me. I want to say something. I'm scared to say something."
Salivary SARS-CoV-2 antigen rapid detection: a prospective cohort study (27 pages)
Diagnostic performance of salivary and naso-pharyngeal swab (NPS) SARS-CoV2 antigen detection
by a rapid chemiluminescent assay (CLEIA) and two different point-of-care
(POC) immunochromatographic assays, was compared with that of molecular testing.
The overall agreement between naso-pharyngeal swab(NPS) and saliva rRT-PC
was 78.7%, reaching 91.7% at one week from symptoms onset.
Quantifying the online news media coverage of the COVID-19 pandemic. (25 pages)
26 million news articles from front pages of 172 major online news sources in 11 countries (available at http://sciride.org).
Sentiment analysis tool Vader was employed
to stratify the emotional polarity of COVID-19 reporting.
COVID-19 coverage accounted for approximately 25% of all front-page online news articles between January and October 2020
16% of COVID-19 news articles (or 4% of all English-speaking articles)
can be classified as highly negatively polarized, citing issues such as death, fear or crisis.
An information overload in COVID-19 reporting risks obscuring effective policy communication.
U.K. fudging AstraZeneca vaccine efficacy numbers?
CEO believes trials will show his firm has achieved vaccine efficacy
equal to Pfizer-BioNTech at 95 percent and Moderna at 94.5 percent,
despite 70% average from earlier trials.
SARS-CoV-2 membrane protein antagonizes type I and III interferon production
by targeting RIG-I/MDA-5 signaling, which subsequently attenuates antiviral immunity
and enhances viral replication (12 pages)
https://www.nature.com/articles/s41392-020-00438-7.pdf
USAFacts/@COVIDTracking now officially updates
between 6PM and 7:30PM Easter Time;
https://covidtracking.com/data
...which does not explain a lack of updates since Dec 25..
EU readies vaccine rollout as new virus strain spreads
The new COVID-19, believed to be more infectious,
has spread from Britain to France and Spain and even as far as Japan.
First doses of the Pfizer-BioNTech vaccine arrived in hard-hit Italy,
Spain and France on Saturday morning ready for distribution to elderly care facilities and staff
My Emergency Room Is Full of Patients No Vaccine Can Help
In the first week of the vaccine rollout, 614,000 Americans were vaccinated
but nearly 1.5 million were diagnosed with COVID-19.
in the months to come, Americans need to double down on simple, proven measures.
That will take the stress off of hospitals and providers.
The importance of continued non-pharmaceutical interventions (NPIs)
during the upcoming SARS-COV-2 vaccination campaign (12 pages)
Continued use of NPIs will be crucial during implementation.
Simulations were generated for all 50 states with the population stratified
by age and priority group. Vaccination (assumed 90% effective 1 week after 2nd dose)
timeline assumed 40 million doses available by the end of December
and 10 million additional doses/week thereafter.
Proportion of U.S. population infected for 7 different combinations of interventions
and 3 different estimates of the basic reproductive number (R0) in the absence of NPI
NV NPIs fully relaxed on December 4th; no vaccination (all others with vaccination)
V1 NPIs fully relaxed on December 4th
V2 NPIs maintained at currently estimated levels
then fully relaxed after vaccination of healthcare workers
V3 NPIs maintained at currently estimated levels
then gradually relaxed after vaccination of essential workers
V4 NPIs strengthened to R0=1.5,
then gradually relaxed after vaccination of essential workers
V5 NPIs maintained at currently estimated levels
then fully relaxed upon vaccination of 100 million people
V6 NPIs strengthened to R0=1.5, then gradually relaxed upon vaccination of 140 million people
Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2 (42 pages)
One of the most variable genes differentiating SARS-CoV-1
and SARS-CoV-2 is the S gene that encodes the spike glycoprotein.
An extensive set of unbiased and biased microsecond-timescale all-atom molecular dynamics
simulations of SARS-CoV-1 and SARS-CoV-2 spike protein ectodomains indicate that
the active form of the SARS-CoV-2 spike protein is considerably more stable
than the active SARS-CoV-1 spike protein. Unlike the active SARS-CoV-2 spike,
the active SARS-CoV-1 spike spontaneously undergoes a large-scale
conformational transition to a pseudo-inactive state.
Oral clarithromycin in COVID-19 of moderate severity:
the ACHIEVE open-label trial using concurrent matched comparators (34 pages)
Clarithromycin treatment is associated with early clinical improvement
in patients with moderate COVID-19. 90 participants with respiratory tract infections
received clarithromycin 500 mg every 12 hours for 7 days; another 90 standard-of-care (SOC)
propensity score-matched concurrent controls received azithromycin plus hydroxychloroquine.
The primary endpoint was attained in 86.7% of patients treated with clarithromycin
and 73.3% of concurrent SOC.
Does COVID-19 Testing Create More Cases? (6 pages)
An Empirical Evidence on the Importance of Mass Testing During a Pandemic
A dataset from the U.S. Department of Health & Human Services empirically showed
that by increasing COVID-19 testing in the U.S., spread of COVID-19 decreased significantly.
California Is 1st State To Hit 2 Million Cases, And Hospitals Are Out Of ICU Beds
The second million took just six weeks.
"If we continue to spread this virus, if we see a linear growth of this for the next two weeks,
we will not have enough medical staff to treat everyone, and hospitals may soon
be in the position of having to ration care. That means that doctors will be forced
to determine who lives and who dies, and more Angelenos will lose their lives,
not just to COVID-19, but to other medical emergencies."
How will you be told when it's your turn for a COVID-19 vaccine? It's complicated.
Vaccine rollout has largely been left to the states
New York's plan says its residents will also be to check a website for a
"vaccine eligibility screening tool and a vaccine administration site locator."
In Maryland, residents will be able preregister for the vaccine
through the state's existing immunization information system.
The CDC's playbook on vaccine distribution says
it will also develop a screening tool for people to determine their own eligibility.
That tool will then point them to VaccineFinder.org, [but not yet, sadly]
an existing platform that connects the public to information about where they can get
seasonal flu vaccines, vaccines for travel and other routinely recommended vaccines.
With vaccines, 3 paths this pandemic nightmare could take
depends not just on science, but how Americans [mis]behave
Best Case: vaccine batches will continue to be distributed with relatively minor hurdles
from here on out, with additional vaccines approved for all ages.
Aggressive vaccinations in May, June, and July could mean
an "overwhelming majority" of the population is vaccinated by August.
Questions about contagion and durability of immunity have good answers.
Nearly everyone who should get the vaccine does get the vaccine,
despite anti-vaccination messaging or prior vaccine hesitancy.
Brutal Setback: Many Americans continue behaving like spoiled brats,
congregating and flouting public health guidelines in January, without having been vaccinated.
562,000 Americans are estimated to have died from COVID-19 by April 1, 2021.
Vaccine reduces risk of getting sick but it doesn't prevent you from spreading it
to someone who hasn't had their shots yet.
Immunity lasts less than the time needed to revaccinate the population.
Russian, neo-Nazi and Trumpian propaganda succeeds in swelling anti-vaxers,
precluding herd immunity without disease, which also confers only temporary immunity.
Messy, Deadly Middle
"We need to be very mindful of the fact that some of the same communities
that have been ravaged by this pandemic are also going to be left high and dry by the vaccine."
"Are we going to reach absolute herd immunity given the percentage of people
who will take it once it's completely available? I think that's going to be a long time."
Moderna Vaccine Causes Side Effects for People With Cosmetic Facial Filler
"In these cases the patients all had swelling and inflammation in the area that was given the filler...
A couple of the patients had cheek filler six months prior to their vaccine
and one patient had lip filler done two days after the vaccine.
All were treated with steroids and anti-histamines and all of their reactions resolved".
Gallinamide A and two lead analogues potently inhibit SARS-CoV-2 infection in vitro.
Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry
and is recognized as a promising drug target. The marine natural product, gallinamide A
and several synthetic analogues, were identified as potent inhibitors of cathepsin L activity.
More than a million people have received their first dose of a COVID-19 vaccine in the U.S.
Three million doses were delivered last week across the U.S.,
with another 6 million vaccine doses by Moderna and 2 million of Pfizer's this week.
The objective of immunizing 20 million people this month is "unlikely to be met."
"The U.S." [Trump's administration] is still "aiming for" 100 million people immunized
by the end of the first quarter of 2021, and another 100 million by the second quarter.
Details on UK SARS-CoV-2 mutations, AKA B.1.1.7
N501Y increases how tightly the spike protein binds to the human ACE2 receptor,
which may make it easier for the virus to take root in those infected.
This mutation is likely why this new variant, first isolated in the UK in late September,
now accounts for more than 60% of new infections in and around London.
A second spike protein mutation, 69-70del, deletes two amino acids,
which may allow the virus to evade some immune responses
and seems to evolve when patients are treated with convalescent plasma.
A third mutation, P681H, occurs in what's called the cleavage site of the spike protein,
which is an area known to affect how readily the virus can enter and kill cells.
Fauci raising herd immunity ante.
In the pandemic's early days, Dr. Fauci tended to cite the same 60-70% estimate as did most experts.
About a month ago, he began saying "70, 75 percent" in television interviews,
and in a CNBC News interview last week, he said "75, 80, 85%" and "75 to 80-plus percent."
In a telephone interview the next day, Dr. Fauci acknowledged that
he had slowly but deliberately been moving the goal posts. He is doing so, he said,
partly based on new science, and partly on his gut feeling that the country is finally
ready to hear what he really thinks. Hard as it may be to hear, he said,
he believes that it may take close to 90% immunity to halt COVID-19
- almost as much as is needed to stop a measles outbreak.
COVID-19 antibodies preferentially target a different part of the virus
in mild cases of COVID-19 than they do in severe cases,
and wane significantly within several months of infection.
"This is one of the most comprehensive studies to date of the antibody immune response
to SARS-CoV-2 in people across the entire spectrum of disease severity" (20 pages)
Endothelial activation and dysfunction in COVID-19:
from basic mechanisms to potential therapeutic approaches (13 pages)
Endothelial cells (ECs) mostly exist in the inner layer of all blood vessels
and are normally protected by pericytes
ACE2 plays a significant role in self-repair of ECs, catalyzing conversion of Ang II.
High Ang II concentrations cause EC death and vascular degeneration
by destroying the connection between ECs and pericytes.
Clinical reports have suggested that the level of Ang II in COVID-19 patients
is considerably higher than that in healthy individuals.
"There's No Place Like Home for The Holidays:"
Travel and SARS-CoV-2 Test Positivity Following Thanksgiving Weekend (8 pages)
Among tested, those who had Thanksgiving outside their home were significantly more likely
to self-report a positive PCR test for SARS-CoV-2 infection in the prior two weeks
compared to those who had Thanksgiving at home with non-household members
or with household members only (41.7% vs. 22.4% or 13.8%, respectively; p<0.001).
Persons who had Thanksgiving outside their home and tested positive for SARS-CoV-2
participated in a median 35 (IQR: 21 - 53). non-essential activities compared to those
who had Thanksgiving at home and tested positive (median 3 activities, IQR 0-13).
Planned travel over December holidays was most common among those who tested positive
for SARS-CoV-2 in the prior 2 weeks (66.5%) compared with 25.4% of those
who tested negative in the prior 2 weeks and 11.0% among those who were not tested.
Toward a COVID-19 testing policy:
where and how to test when the purpose is to isolate silent spreaders (34 pages)
Test positivity (TP) based analysis discovered municipalities
where selective testing would be more cost effective than alternatives.
When TP is low and/or the Tests/Cases ratio is high,
testing detects asymptomatic cases and COVID-19 related deaths/mi are low.
Georeferenced TP data can support cost-effective, site specific policies.
TP promotes the prompt cessation of epidemics and fosters science based testing policies.
Direct RNA nanopore sequencing of SARS-CoV-2 extracted from critical material from swabs
This approach provides the advantages of true native RNA sequencing,
and does not include amplification steps that could introduce systematic errors. (14 pages)
https://www.medrxiv.org/content/10.1101/2020.12.21.20191346v1.full.pdf+html
Some local governments and workplaces are using algorithms
- glorified Excel formulas in some cases - to decide who gets the first vaccines;
computers aren't necessarily making great decisions.
The Stanford backlash is just "a harbinger of things to come."
COVID-19 Variant Could Make Herd Immunity More Difficult
That threshold for immune percent of population to achieve herd immunity
is related to the speed of the viral spread, known as R.
Most experts agreed the herd immunity threshold for COVID-19 was between 60% and 70% of a population.
Should the new variant boost the R number of COVID-19, more immunization will be required
Suspicions grow that nanoparticles in Pfizer's COVID-19 vaccine trigger rare allergic reactions
A similar mRNA vaccine developed by Moderna,
which was authorized for emergency use in the U.S. on Friday,
also contains the compound, polyethylene glycol (PEG).
PEG has never been used before in an approved vaccine,
but it is found in many drugs that have occasionally triggered anaphylaxis.
Tennessee now leads the country in cases per capita,
thanks in part to Thanksgiving gatherings that spread the virus.
"If we have another surge over Christmas, it will break our hospitals,"
the state's health commissioner warned Sunday.
Nevertheless, Gov. Bill Lee (R) has refused to order a mask mandate.
Fauci: "When you see something that is pretty prevalent in a place like the UK
- there are also mutations that we're seeing in South Africa -
and given the travel throughout the world, I would not be surprised if it is already here"
[ so, may as well let more in...???!!! ]
https://www.eatthis.com/news-fauci-covid-mutation-usa/
DHEC picks military official and doctor Edward Simmer as new director
to run SC health and environmental agency, a post vacant since last summer.
Simmer has served as the chief clinical officer for the TRICARE Health Plan at the Defense Health Agency.
The board's pick must be approved by Gov. Henry McMaster and the state Senate,
meaning it could be late winter before that person is confirmed and on the job.
Mask wearing declines, even as COVID-19 touches more U.S. lives
66% of U.S. adults surveyed in a new HealthDay/Harris Poll said
they "always" donned a mask when leaving their home and weren't able to socially distance,
compared with 72% in a poll conducted in October
Are college campuses superspreaders? [yes] A data-driven modeling study. (13 pages)
A classical mathematical epidemiology model and Bayesian learning were integrated
to obtain the dynamic reproduction number for 30 colleges from their daily case reports.
14 displayed a spike of infections within the first 2 weeks of class,
with peak 7-day incidences well above 1,000 per 100,000,
an order of magnitude larger than nation-wide pandemic peaks.
Within 2 weeks, 17 campus outbreaks translated to peaks of infection within those counties.
U.S. Ban on U.K. Flights Isn't Needed, Virus Team Member Says
Eleven countries, most in Europe, have suspended flights from the UK
Canada was the latest to announce a ban on Sunday night
Howard Zucker, NY commissioner of health, said testing hasn't turned up any cases of the variant,
but Cuomo compared the situation to the spring, when COVID-19 arrived largely via Europe.
He said six flights are arriving each day from the U.K. to New York.
U.S. cannot rely solely on individuals to stop COVID-19
Despite recent surges in Europe and Israel, the U.S. remains within the top 20%
for most COVID-19 deaths per person among developed nations,
with more than twice the death rate as the median developed country.
People who are ages 75 and older and frontline essential workers should be next in line
to get a COVID-19 vaccine, a federal advisory committee to the CDC determined Sunday.
Federal officials anticipate having enough doses by the end of February 2021
to immunize around 100 million - around a third of the U.S. population.
"We will need some very clear communication and talking points as to
why frontline essential workers, who may be younger and healthier, are being vaccinated
over [people ages 65 to 74] and those with multiple underlying health conditions"
The story of Regeneron's COVID-19 antibody quest
Regeneron works with "magic mice", which don't get sick when vaccinated with virus parts
but make "almost identical antibodies to what humans would make."
It takes just 20 to 30 of these mice to develop a drug.
The SARS-CoV-2 RNA-protein interactome in infected human cells (25 pages)
Up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs
in infected human cells were identified using RNA antisense purification and mass spectrometry.
RNA from infected cells was extracted for both SARS-CoV-2 and human ribonuclease mitochondria
as a control. 104 human proteins were found to bind SARS-CoV-2 RNA,
of which 100 have been identified previously.
Only 10 human proteins that bound recombinant SARS-CoV-2 proteins in uninfected cells
also bound directly to viral RNA in infected cells.
Results were validated by inhibiting interactome proteins with known pharmacological agents.
Epidemiological feature, viral shedding, and antibody seroconversion
among asymptomatic carriers and symptomatic/ presymptomatic COVID-19 patients (29 pages)
Compared to symptomatic patients, asymptomatic carriers were younger
and had higher levels of white blood cell and lymphocyte,
lower levels of C-reactive protein and viral load, and shorter viral shedding duration.
Viral load was higher in symptomatic than presymptomatic patients.
Viral shedding was longer in presymptomatic patients than in asymptomatic carriers.
Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2
than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.
expensive clinics buying up ultra-low temperature freezers needed to store Pfizer vaccine
Exclusive California doctors received hundreds of calls
from clientele attempting to skip COVID-19 vaccine queue.
According to physician Jeff Toll, one client offered a five-figure donation to Cedars-Sinai Medical Center,
one of the first CA hospitals to receive vaccines where he also has admitting privileges.
Beginning Monday, 5.9 million doses of Moderna vaccine will go out
in addition to 2 million more doses of Pfizer-BioNTech vaccine,
bringing a total of 7.9 million more doses to the U.S..
Drug distributor McKesson Corp. began picking up doses of the vaccine
from manufacturing plants on Saturday for distribution around the country.
UPS and FedEx trucks will start rolling out Sunday to deliver the doses to hospitals and other sites.
Tocilizumab in Patients Hospitalized with COVID-19 Pneumonia
In hospitalized COVID-19 pneumonia patients not already receiving mechanical ventilation,
tocilizumab reduced likelihood of progression to ventilation, but did not improve survival rate.
Current evidence for COVID-19 therapies: a systematic literature review (55 pages)
42 clinical trials were included. Interventions assessed included antiviral, mucolytic,
anti-malarial, anti-inflammatory and immunomodulatory therapies. Some reductions
in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir,
particularly when administered early, and with the mucolytic drug, bromhexine.
Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy
over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation
and need for ventilation versus standard care, particularly in patients with severe disease.
Evidence for other classes of interventions was limited.
Many trials had a moderate-to-high risk of bias, particularly in terms of blinding;
most were short-term; and some included low patient numbers.
FDA EUA granted to Moderna COVID-19 Vaccine mRNA-1273
https://www.fda.gov/media/144636/download
Early results of large, still unfinished studies show both vaccines appear safe
and strongly protective although Moderna's is easier to handle
since it doesn't need to be stored at ultra-frozen temperatures.
Moderna has about 5.9 million doses ready for shipment set to begin over the weekend.
Novavax stock climbs +9.2% after agreeing to supply 10.7M doses of its vaccine candidate,
NVX-CoV2373, with initial doses from mid-2021, subject to the approval of Medsafe,
New Zealand's regulatory agency. The recombinant protein COVID-19 vaccine,
adjuvanted with Novavax' proprietary Matrix-M to boost immune response,
is currently undergoing a Phase 3 clinical trial in the UK.
neutralizing nanobodies
Monoclonal antibodies that bind to SARS-CoV-2 spike protein
must be produced in mammalian cells and delivered intravenously.
Single-domain antibodies, called nanobodies, can be produced in bacteria or yeast,
and their stability may enable aerosol delivery.
Schoof et al. screened a yeast surface display of synthetic nanobodies (8 pages)
https://science.sciencemag.org/content/sci/370/6523/1473.full.pdf
and Xiang et al. screened anti-spike nanobodies produced by a llama. (7 pages)
https://science.sciencemag.org/content/sci/370/6523/1479.full.pdf
Both identified highly potent nanobodies that lock the spike protein in an inactive conformation.
Multivalent constructs of selected nanobodies achieved even more potent neutralization.
Boris Johnson backtracks on relaxing Christmas rules
after scientists warn new COVID-19 strain spreads faster
As with other new variants or strains, this one is easily tracked by its genetic fingerprint,
and it happens to be one that is now common.
That does not mean the mutation has made it spread more easily,
nor does it not necessarily mean this variation is more dangerous.
Chinese and Russian vaccines remain unproven
- but desperate countries plan to use them anyway
"There's no reason to think these vaccines won't work, but we have not seen Phase 3."
Scientists get the most realistic view yet of a coronavirus spike's protein structure
Their method, which combines cryogenic electron microscopy (cryo-EM) and computation,
should produce quicker and more realistic snapshots of the infection apparatus
in various strains of coronavirus, a critical step in designing therapeutic drugs and vaccines.
Rather than chemically removing and purifying NL63's spike proteins,
researchers flash-froze whole, intact viruses into a glassy state
that preserves components' natural arrangements.
Then they made thousands of detailed images of randomly oriented viruses
using cryo-EM instruments at the Stanford-SLAC Cryo-EM Facilities,
digitally extracted the bits that contained spike proteins,
and combined them to get high-resolution pictures. Their map included
three glycosylation sites that had been predicted but never directly seen before.
Cologne University Hospital, University of Marburg,
the German Center for Infection Research and Boehringer Ingelheim
today initiated Phase 1/2a clinical trial of BI 767551,
a SARS-CoV-2 neutralizing antibody derived from blood samples of recovered COVID-19 patients.
"With BI 767551, we aim to provide an effective option for preventing and treating COVID-19"
https://medicalxpress.com/news/2020-12-sars-cov-neutralizing-antibody-clinical-phase.html
Transcriptomic, epigenomic, and proteomic single-cell immune profiling
of 64 COVID-19 patients across the full range of disease severity,
from outpatients with mild disease to fatal cases,
reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19,
with the most profound disturbances including a prominent neutrophil hyperactivation signature
and monocytes with anti-inflammatory features.
Emergency myelopoiesis [production of bone marrow and of all cells that arise from it]
is a prominent feature of fatal COVID-19.
Results reveal disease severity-associated immune phenotypes in COVID-19
and identify pathogenesis-associated pathways
that are potential targets for therapeutic intervention. (40 pages)
https://www.biorxiv.org/content/10.1101/2020.12.18.423363v1.full.pdf
Among counties tracked, nearly half seemingly have over 1% of residents currently infected COVID-19, the gift that keeps giving
Several states say they have been told to expect far fewer doses of Pfizer-BioNTech COVID-19
vaccine in its second week of distribution, prompting worries about potential delays in shots
for health care workers and long-term care residents.
Pfizer said its production levels have not changed. [Like Tennessee, feds are squirreling doses]
"We are continuing to dispatch our orders to the locations specified by the U.S. government."
SARS-CoV-2-like particles on surfaces very sensitive to temperature (4 pages)
Just moderate temperature increases broke down the virus' structure,
while humidity had very little impact. "What's surprising is how little heat was needed
to break them down - surfaces that are warm to the touch, but not hot.
The packaging of this virus is very sensitive to temperature."
Viral targets for vaccines against COVID-19 (10 pages)
Describes and tabulates 16 vaccines and candidates
7 strategies: Inactivated, Live attenuated, Protein subunit, Virus-like particles,
Virus vectored, mRNA, DNA
" It is worth noting that it is currently difficult to compare the various vaccines
as there are no standardized assays for neutralization and challenge studies."
Early lockdowns were key in reducing ultimate COVID-19 spread
researchers measured the "openness" of states using an index developed by WalletHub,
which scored states based on a range of restrictions, such as requirements to wear masks
in public, reopening of restaurants and bars, and guidance for assisted living facilities.
WalletHub re-scored states nine times between May 5 and Oct. 5 as their restrictions changed.
The higher a state's per capita deaths in March and April,
the more likely the state was to adopt strict restrictions by May 5.
Since July, correlation between deaths and openness has not only remained positive but also strengthened
Did the FDA understaff its review of the Pfizer/BioNTech vaccine?
Unlike its counterparts in other countries, the FDA is believed to be
the only drug regulator in the world that consistently receives and reviews
patient-level data from the clinical trials that underpin drug and vaccine approvals.
"By assigning only one clinical, one statistical, and one toxicology scientist
to review the Pfizer/BioNTech COVID-19 vaccine, it seems that discussion,
let alone disagreement, was curtailed by design.
The pressure on those lone FDA reviewers to do their work in record time,
and do it without raising serious questions about the data, was likely immense."
several thousand doses of COVID-19 vaccine in California and Alabama quarantined
an "anomaly" in the transportation process caused the storage temperature to get too cold.
"We returned them immediately back to Pfizer
and we sent immediate shipments to replace those two trays."
Operation Warp Speed delivered 2.9 million doses of Pfizer's vaccine this week.
SC lawmakers want to take steps against any federal mask rule
S.C. Reps. Mike Burns, Bill Chumley and Stewart Jones, all Republicans,
filed a bill last week that would fine any employee, department or official of the state $2000
for enforcing a nationwide mask requirement issued by the president, Congress
or any federal agency.
CoV2-ID, a MIQE-compliant sub-20-min 5-plex RT-PCR assay https://en.wikipedia.org/wiki/MIQE
targeting SARS-CoV-2 for the diagnosis of COVID-19 (13 pages)
It is robust, can consistently detect two copies of viral RNA,
with a limit of detection of a single copy and can be completed in around 15 min.
It was 100% sensitive and 100% specific when tested on 23 RNA samples
extracted from COVID-19 positive patients and five COVID-19 negative patients.
Determinants of SARS-CoV-2 transmission to guide vaccination strategy in a city
Transmissions on the city population level are driven by the socioeconomically weaker and highly mobile groups.
Simulated vaccination scenarios showed that vaccination of a third of the population at 90% efficacy
prioritizing the latter groups would induce a stronger preventive effect
compared to vaccinating exclusively senior population groups first.
Efficacy and Safety of Indomethacin in COVID-19 patients (23 pages)
[ If you can get a doctor to prescribe Indomethacin,
it would be good to have on hand to take in the event of suspected COVID-19 infection...
For example, it has been prescribed for sciatica or rheumatoid arthritis. ]
Indomethacin, along with standard care, seems to provide faster symptomatic relief
and prevent progression of pneumonia in COVID-19 patients.
It should be considered to replace paracetamol when there is no contraindication for its use.
Patients treated with Indomethacin had a reduction in the number of days to become afebrile,
reduction in cough and myalgia by half compared to the paracetamol set.
Only one out of 72 patients in the Indomethacin arm of the first group
required supplementary oxygen while 28 of the 72 patients required supplementary
oxygen in the paracetamol arm. No one in the second group deteriorated enough to
require mechanical ventilation. There was no evidence of adverse reaction to
indomethacin or deterioration of renal or liver function.
Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID)
commonly used as a prescription medication to reduce fever, pain, stiffness,
and swelling from inflammation. https://en.wikipedia.org/wiki/Indometacin
Instead of inoculating vulnerable, Tennessee first vaccine shipment is emergency backup
[ I expect that it will subsequently be mysteriously misplaced ]
The state expects to receive a second COVID-19 vaccine shipment (56,550 doses) on Wednesday,
which will then be shipped Thursday to 28 sites to serve 74 hospitals.
Another 56,500 dose shipment is expected three weeks later.
Hilton Head, Coastal Carolina hospitals receive 1st COVID-19 vaccine shipment
The medical centers should begin vaccinating employees later Wednesday
Beaufort Memorial Hospital had not received doses as of early Wednesday.
The Medical University of South Carolina, Prisma Health and Lexington Medical Center
all began to inoculate staff Tuesday. Conway Medical Center administered doses on Monday.
Genetic architecture of host proteins involved in SARS-CoV-2 infection (14 pages)
Like all viruses, SARS-CoV-2 depends on host cell proteins to replicate.
Scientists from the United Kingdom, Germany and the U.S. have collaborated to identify
protein genetic variations that affect this, publishing results here:
https://omicscience.org/apps/covidpgwas/
"As molecular epidemiologists, we study the diversity of genes - that is,
the building instructions for proteins - of entire population groups
in order to uncover susceptibilities to diseases
whose cause lies in the interaction of many small deviations.
Journal articles that used our findings appeared
even before our work was officially published.
This is exactly what we had hoped for."
Forecasting the next COVID-19 (6 pages)
The Global Immunological Observatory, like a weather center forecasting a tornado or hurricane,
would alert the world, earlier than ever before, to dangerous emerging pathogens like SARS-CoV-2.
"We're going to do our damnedest to try and make it happen, because it would be crazy not to."
Two phases of infection in patients with severe COVID-19 pneumonia (15 pages)
The early phase is defined by high levels of virus in lungs that trigger patients' cells
to express genes involved with the interferon pathway, key to immune response.
In the later phase, virus is no longer present, but lung damage is too severe for recovery.
Sputnik V Vaccine Demonstrates 91.4 Percent Efficacy
Out of 78 confirmed infections among 22,714 participants,
62 were in individuals who received a placebo.
No severe COVID-19 infections were found in participants who received the vaccine,
while 20 severe cases were reported in the placebo group.
Inferring the effectiveness of government interventions against COVID-19 (17 pages)
Closing all educational institutions, limiting gatherings to 10 people or less,
and closing face-to-face businesses each reduced transmission considerably.
The additional effect of stay-at-home orders was comparatively small.
FDA Finds Moderna COVID-19 Vaccine Highly Effective
Second major U.S. mRNA vaccine could possibly be shipped by this weekend
New data suggests its vaccine begins to prevent asymptomatic infections after the first dose.
A humidifier could help ward off COVID-19, but don't overdo it
The nose is a fantastic filter for viruses and other foreign particles,
but it does not work as well when the air is dry
- a drawback that could explain some of the recent surge in COVID-19.
Try to maintain relative humidity in the 40%-to-60% range.
Bill Gates: "Well, sadly, the next four to six months could be the worst of the epidemic.
Certainly by the summer, we'll be way closer to normal than we are now,
but even through early 2022, unless we help other countries get rid of this disease,
and we get high vaccination rates in our country, the risk of reintroduction will be there."
New COVID-19 strain: How worried should we be?
There is no clear-cut evidence the new COVID-19 variant - detected in south-east England -
is able to transmit more easily, cause more serious symptoms or render the vaccine useless.
It has two notable mutation sets:
* N501 alters the most important part of the spike, known as the "receptor-binding domain".
* H69/V70 deletion has emerged several times before, including famously in infected mink.
"Even though a new genetic variant of the virus has emerged and is spreading
in many parts of the UK and across the world, this can happen purely by chance."
Another, earlier, variant (G614) is seen by many as the virus getting better at spreading.
Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion H69/V70 (19 pages)
H69/V70 increases Spike-mediated infectivity by approximately two fold
and therefore may be a compensatory mechanism for putative antibody escape mutations in Spike.
Enhanced surveillance for this deletion with and without RBD mutations should be considered as a priority.
COVID-19 mutation - not as scary as it sounds [ perhaps, but not addressed in this article ]
About 1/5 of your body is made up of proteins, which are strings of amino acids.
There are just 20 types of amino acid with which to build all the proteins on Earth,
which combine to make your estimated 6 million different types of protein.
Mutations affect the number or type of amino acids that make up a particular protein;
most mutations lead to no beneficial change in protein properties at all, and
those that change proteins' properties are more likely to weaken than strengthen a virus.
Endothelial cell targeting could help fight COVID-19 symptoms (7 pages)
"A transformative change in the mechanism of endothelial cell dysfunction,
not the infection of the cells themselves,
changes the way in which disease is initiated and rationales for therapeutic targeting."
Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a
and mobile phone microscopy (21 pages)
Quantitative, accurate, portable and low-cost point-of-care detection of SARS-CoV-2
with a measurement time as low as 5 minutes.
A key advance in this work is demonstrating that combinations of crRNAs
can increase sensitivity by activating more Cas13a per target RNA.
What vaccine distribution planners can learn from Amazon and Walmart
Any time there is a mismatch between supply and demand, there is waste.
Instead of shipping vaccines directly to hospitals and pharmacies,
states could set up regional "fulfillment centers" in different counties with pooled inventory
that can restock vaccination sites on demand in smaller batches for just-in-time immediate use.
One way to minimize storage needs is to use an approach called cross-docking.
Instead of taking deliveries from incoming trucks to warehouses,
simply move goods across a loading dock directly to outgoing trucks,
eliminating a need for freezers at intermediate warehouses.
Who is doing all those COVID-19 tests?
Why you should care about medical laboratory professionals:
laboratory testing is the single highest-volume medical activity in American life,
driving approximately 2/3 of medical decisions.
With competition for laboratory personnel intensifying over the last year,
turnover rates for some categories now exceed 20%.
COVID-19 Changed Science Forever - The Atlantic [click bait]
"Clinicians wasted millions of dollars on trials that were so sloppy as to be pointless.
Overconfident poseurs published misleading work on topics in which they had no expertise."
Warped incentives, wasteful practices, overconfidence, inequality, a biomedical bias
- COVID-19 has exposed them all.
[ in other words, monkey business as usual ]
In March, taking advantage of the United Kingdom's nationalized health system,
British researchers launched a nationwide study called Recovery,
which has since enrolled more than 17,600 COVID-19 patients across 176 institutions.
Recovery offered conclusive answers about dexamethasone and hydroxychloroquine
and is set to weigh in on several other treatments.
No other study has done more to shape the treatment of COVID-19.
Minimal system for assembly of SARS-CoV-2 virus like particles (5 pages)
Non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled
by co-expressing viral proteins S, M and E in mammalian cells.
These VLPs possess S protein spikes on their exterior,
making them ideal for vaccine development.
SARS-CoV-2 VLPs dried in ambient conditions
can retain their structural integrity upon repeated scans with Atomic Force Microscopy
Gene expression network analysis provides potential targets against SARS-CoV-2 (9 pages)
Weighted gene correlation network analysis of 1,038 lung tissue
samples identified and characterized dozens of genes that are
co-expressed with ACE2 and transmembrane serine protease 2 (TMPRSS2),
many of which have plausible links to COVID-19 pathophysiology
and are potentially targetable with existing drugs.
Why many countries failed at COVID contact-tracing - but some got it right
"By now, what I was expecting is that 100% of people coming in contact
with COVID-19 would have been traced" In some regions of the U.S.,
more than half of people who tested positive in November
provide no details of contacts when asked.
SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome (37 pages)
Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests
have been widely reported in patients after recovery, yet these
patients most commonly are non-infectious.
Experimental support for the possibility that SARS-CoV-2 RNAs
can be reverse-transcribed and integrated into the human genome
and that transcription of the integrated sequences
might account for PCR-positive tests.
A novel cell culture system modeling the SARS-CoV-2 life cycle (42 pages)
A biosafety level-2 (BSL-2) cell culture system for production of transcription
and replication-competent SARS-CoV-2 virus-like-particles (trVLP) is developed.
A 96-well format high throughput screening for antivirals discovery was developed
and identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride
and nigericin sodium as potent antivirals against SARS-CoV-2 infection.
COVID-19 politics result in pandemic winners and losers
It's telling that politicians mandate restaurants to increase social distancing
and institute enhanced health and cleaning protocols for the safety of guests,
but do little to improve the working conditions of the staff in the kitchen.
Locking long-term care residents in their rooms for months, especially those
not infected with COVID-19, reflects the lack of political power held by this group.
SARS-CoV-2 at 1: A year into the pandemic,
what scientists know about how it spreads, infects, and sickens
"It's got its own character, so to speak, but there's nothing really
out of the ordinary, it's not that weird"
The single advantage that's propelled its around-the-world quest:
People can pass it to others before they start feeling sick
or even if they never show symptoms.
Though it's tempting to anthropomorphize viruses,
they're not really alive in the ways we normally imagine that state of being.
They're more like replicating Roombas
[ No Dec 14 COVID-19 data update from USAFacts as of 4PM;
perhaps they were preoccupied with Electoral College results.... ]
All hospital ICU beds filled in San Joaquin Valley region amid COVID-19 surge
The region, comprised of 12 counties in central California,
along with the enormous Southern California region, contain more than 60% of the state's 40 million residents.
Last week, the two regions were ordered to follow the strictest anti-COVID-19 rules
under a new state stay-at-home order that aims to keep hospitals from being overwhelmed by restricting infectious contacts.
This weekend, 2.9 million doses of the COVID-19 vaccine developed by Pfizer and BioNTech
are set to travel by plane and guarded truck from Michigan and Wisconsin to designated locations,
mostly hospitals, in all 50 states. Pfizer said the first shipment would leave its Kalamazoo plant
early Sunday morning. First injections are expected to be given
by Monday to high-risk health care workers. 145 sites are expected to get doses Monday,
another 425 sites should receive deliveries Tuesday,
while 66 remaining sites are slated to get their supplies Wednesday
First delivery locations were chosen because they all have ultracold freezer capacity.
In the case of UPS, all vaccine going into its shipping system on Sunday
will be flown on a dedicated plane from Michigan to its main hub in Louisville, Kentucky.
After Sunday, vaccine cartons will go by truck to Louisville. Each carton will have a GPS tracker,
allowing it to be located in real-time anywhere in the world,
as well as a Bluetooth tracker that can locate it within 10 feet inside a UPS facility
COVID-19 vaccines are on the way to SC,
but it's still unclear when they'll arrive in Beaufort and Jasper counties.
Beaufort Memorial Hospital lacked ultra-cold freezers as of early December.
After setting aside roughly half of the initial December allocation
to vaccinate long-term care residents and staff through CVS and Walgreens,
the state has yet to name 15 specific locations initially getting vaccine..
Those 15 sites can redistribute vaccine to their "affiliated" locations;
there could be up to 56 sites by the end of this week
COVID-19 vaccines can't arrive soon enough for many frontline health workers
Some younger nurses were unsure if they would take the vaccine
because they worried about effects it could have on future pregnancies.
"I recognize this is going to be an unpopular thing to say, but it's just the cold mathematics.
Vaccinating health care workers won't materially lower the overall mortality rate."
How to stay connected and resilient in a COVID-19 holiday season
One of the biggest boosts we can give ourselves is to give to others.
Self-transcendent emotions, which include compassion and gratitude,
have a positive physiological impact by stabilizing our heart rate and blood pressure.
In fact, giving to others stimulates the brain's reward centre, and that's why it feels so good.
Try to pick activities that use your hands and your body.
Art and crafts, photography, exercise and playing a musical instrument
can all provide a means to focus our attention on a specific and in in-the-moment task.
Researchers rank various mask protection, modifications against COVID-19
Masks made of two layers of woven nylon, fitting snugly against faces are 79% effective.
Unmodified surgical masks with ear loops offered 38.5% filtration efficacy,
but when the ear loops were tied in a specific way to tighten fit, efficacy improved to 60.3%.
When a layer of nylon was added, these masks offered 80% effectiveness.
[ click FIGURES/TABLES]
IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2 (19 pages)
An IGI-LuNER RT-qPCR assay uses the Luna Probe Universal One-Step RT-qPCR master mix
with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER).
This combined, cost-effective test can be performed in 384-well plates
with detection sensitivity suitable for clinical reporting,
and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection.
The IGI-LuNER assay is estimated to cost $1.26 per reaction,
a 6-12x reduction in cost from other commercially available tests.
Sanofi-GSK COVID-19 vaccine delayed after disappointing results in older patients
"an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years,
but a low immune response in older adults likely due to an insufficient concentration of the antigen".
Sanofi said it would instead launch a phase 2b study in February.
"The study will include a proposed comparison with an authorized COVID-19 vaccine"
Sanofi is working on another COVID-19 vaccine candidate with U.S. company Translate Bio which uses mRNA technology. Phase I trials are expected to start this month.
Adding baricitinib to remdesivir was associated with shorter recovery time,
particularly among patients receiving high-flow oxygen,
and with a 30% higher odds of improvement at day 15 than remdesivir alone.
Adverse events were less frequent with the combination therapy,
in a trial involving 1033 COVID-19 patients.
SARS-CoV-2 may invade the central nervous system
either through a porous bone in the nasal cavity
(which causes the loss of smell and/or taste commonly experienced with COVID-19),
or through the body's circulatory system, subsequently crossing the blood-brain barrier.
America's Bipartisan COVID-19 Illiteracy - The Atlantic
Federal health guidance oscillates between being a vacuum and an epistemic horror show.
In the pandemic's 9th month, U.S. public-health responses make as little sense as ever.
The Next Six Months Will Be Vaccine Purgatory
Each state ultimately decides how to allocate the vaccines it receives.
A person who qualifies as an essential worker in Illinois might not in Indiana.
Structural and functional comparison of SARS-CoV-2-spike receptor binding domain
produced in Pichia pastoris and mammalian cells (18 pages)
The yeast Pichia pastoris is a cost-effective
and easily scalable system for recombinant protein production.
This work compares SARS-CoV-2 Spike protein receptor binding domain (RBD)
grown in P. pastoris and in the well established HEK-293T mammalian cell system.
High-performance liquid chromatography (HPLC) profile analysis
revealed that RBD produced in HEK-293T cells is highly homogeneous,
as shown by its elution as a sharp peak at 48-49% of acetonitrile in a reverse phase C18 column,
while RBD produced in P. pastoris showed a considerably broader peak,
although it eluted at very similar acetonitrile concentration. In addition,
two very small peaks appeared in the chromatogram of RBD produced in P. pastoris.
The area corresponding to the full-length protein was approximately 87%.
Blockage of interleukin-1B with canakinumab in patients with COVID-19 (9 pages)
This was a "Hail Mary" study, with no blind controls and patients with comorbidities on oxygen
who had already received a variety of empirical treatments given on a compassionate basis.
Authors concluded that canakinumab was well tolerated, improved oxygenation,
and decreased systemic inflammatory response.
Individual and community-level risk for COVID-19 mortality in the U.S. (23 pages)
A web-based risk calculator that allows an individual to input information on risk factors
and obtain estimates of individualized risk for COVID-19 mortality
on both relative and absolute risk scales
https://covid19risktools.com:8443/riskcalculator
The Index of Excess Risk (IER) varies around tenfold and eightfold
across cities and counties for the underlying adult
and 65-years-and-older Medicare populations, respectively
COVID-19 vaccine distribution timeline keeps slipping.
Package delivery companies FedEx and UPS are involved in distributing Pfizer's vaccine,
and both face their own limitations, especially during the holiday season.
Wastage of between 1% and 10% is fairly common.
Optimal test allocation strategy for COVID-19 (25 pages)
An online calculator:
https://umich-biostatistics.shinyapps.io/Testing_Optimization/
The framework accounts for imperfect test results,
testing in certain high-risk patient populations,
practical constraints in terms of budget and/or total number of available tests,
and the goal of testing. They extend the model for
allocating two different types of tests with different cost and accuracy.
COVID-19 Test Strategy to Guide Quarantine Interval in University Students (11 pages)
16% positive rate supports an ongoing need to quarantine close contacts of COVID-19 cases;
this prospective study provides direct evidence that exposed asymptomatic students
ages 18-44 years in a university setting are at low risk
if released from quarantine at 7 days if they test negative PCR test prior to release.
Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic:
a simulation analysis (28 pages)
Routine asymptomatic testing for COVID-19 prior to travel
can be an effective strategy to reduce individual risk of COVID-19 infection during travel,
although post-travel testing with abbreviated quarantine is likely needed
to reduce population-level transmission due to importation of infection
when traveling from a high to low incidence setting.
Genomic epidemiology of superspreading events in Austria (14 pages)
Austria has both well-developed epidemiological surveillance system
and a key role in spreading COVID-19, thanks to visitors from China to its ski resorts/
This study illustrates the power of combining epidemiological analysis
with deep viral genome sequencing to unravel the spread of SARS-CoV-2
and to gain fundamental insights into mutational dynamics and transmission properties.
Johnson & Johnson is cutting the size of its U.S. COVID-19 vaccine trial
- the only major study testing a single dose of a COVID-19 vaccine - from 60,000 to 40,000 volunteers,
because increased infection rate should result in equivalent statistical significance.
"We continue to anticipate that interim data from the ENSEMBLE trial will be available by the end of January.
If the vaccine is safe and effective, an EUA application could be submitted to the FDA in February."
New data, dashboard provide information on COVID-19 hospital capacity
In addition to describing data in detail and providing links to potential outside resources
(such as census data and hospital cost data from the Centers for Medicare and Medicaid Services),
it addresses questions users of these data may have. It includes an interactive dashboard
to visualize hospital capacity at the county-level for the entire U.S. or selected state[s].
https://carlsonschool.umn.edu/mili-misrc-covid19-tracking-project
Prioritising COVID-19 vaccination in changing social and epidemiological landscapes (13 pages)
If starting sufficiently early in 2021, a strategy of vaccinating individuals
60 years of age and older will prevent the most deaths,
but if the vaccine is not available until later in 2021,
we might be able to prevent more deaths by first vaccinating younger age groups
- working-age adults and children - who have more contacts with others.
COVID-19 vaccines focus on its spike protein - but here's another target
Patients actually make the most antibodies to the N protein - not the spike protein,
but N protein is only found inside the virus particle, wrapped around the RNA.
Therefore, N protein antibodies cannot block virus entry,
will not be measured in neutralisation assays that test for this in the lab,
and so have largely been overlooked. This research revealed a new mechanism
for an antibody receptor called TRIM21, which recognizes N protein antibodies
that get inside cells, then shreds the associated N protein.
Tiny fragments of N protein are then displayed on the surface of infected cells.
T cells recognise these fragments, identify cells as infected,
then kill the cell and consequently any virus.
Combining modeling from 40 independent research groups, a new composite forecast
from the U.S. CDC projects a total of 332,000 to 362,000 COVID-19 deaths by January 2.
COVID-19 hospitalizations reached a new high of 106,688 on Wednesday.
https://www.cnn.com/2020/12/10/health/us-coronavirus-thursday/index.html
Pfizer COVID-19 vaccine faces last hurdle before U.S. decision
A U.S. government advisory panel convened on Thursday
to decide whether to endorse mass use of Pfizer's COVID-19 vaccine.
Depending on how fast the FDA signs off on the panel's recommendation,
shots could begin within days. [ U.K. allergy reports may delay this ]
New serological assay provides rapid, accurate testing for SARS-CoV-2 antibodies
ELISA takes 4-6 hours and provides quantitative results indicating immune response strength.
Simpler assays using test strips provide rapid results
but are less reliable and do not quantify antibody levels.
The new method, called biolayer interferometry immunosorbent assay
(BLI-ISA), provides complete quantitative results in less than 20 minutes.
"Our assay is as sensitive if not better than other assays in detecting low levels of antibodies,
and the specificity [false-positive rate] is as good as the best antibody tests out there"
Transmembrane protein 41 B (TMEM41B) is essential for SARS-CoV-2 to replicate.
"While inhibiting transmembrane protein 41 B is currently a top contender for future therapies
to stop coronavirus infection, our results identified over a hundred other proteins
that could also be investigated as potential drug targets"
Rapid and sensitive detection of SARS-CoV-2 antibodies by biolayer interferometry (12 pages)
Biolayer interferometry immunosorbent assay (BLI-ISA) utilizes single-use biosensors
in an automated "dip-and-read" format, providing real-time optical measurements
of antigen loading, plasma antibody binding, and antibody isotype detection.
Complete semi-quantitative results are obtained in less than 20 min.
BLI-ISA meets or exceeds the performance of high complexity methods
such as Enzyme-Linked Immunosorbent Assay (ELISA) and Chemiluminescent Immunoassay.
Importantly, the method can be immediately implemented
on existing BLI platforms for urgent COVID-19 studies,
such as serosurveillance and the evaluation of vaccine candidates
Daily DIY sniff checks could catch many cases of COVID-19
44% to 77% of people with COVID-19 lose their sense of smell,
but many are unaware they have anosmia
until they actively try to smell something that should have an odor, like scented candles.
Steroids are a powerful COVID-19 treatment. We need to learn to use them better.
Approximately one in 25 people with COVID-19 need hospitalization,
and about 9% of them end up having acute respiratory distress syndrome (ARDS).
These often present with features of cytokine storm syndrome, which may be treated
with drugs such as prednisone, methylprednisolone, and dexamethasone,
but these drugs must be given at the right time for best outcomes,
and there is still much to learn about how these work in the case of COVID-19.
U.S. hospitals running out of ICU beds for COVID-19 patients
More than a third of Americans now live in areas where hospitals are critically short
of intensive care beds. Hospitals serving more than 100 million Americans had fewer than
15% of ICU beds still available as of last week, per NY Times analysis of government data.
Across much of the Midwest, South and Southwest, ICU are either completely full
or fewer than 5% of beds are available.
For the first time, the U.S. will incent nursing homes to control infectious disease spread.
For years, nursing homes have been shaped by federal incentives,
which pay for extra services but not measures that would combat disease spread.
That left residents acutely vulnerable to COVID-19. Now,
more than 9,000 nursing homes have been able to show progress in controlling COVID-19 infection,
according to the Department of Health and Human Services,
and will share $523 million in incentive payments, starting Wednesday.
To defeat COVID-19, we must acknowledge the fear it engenders
Fear can be much more powerful than science.
Re: March N95 mask shortage and PPE rationing
What I wanted the staff to understand from this distribution method was,
"I care about you, so I want there to be enough N95s available when the hospital
was full of COVID-19 patients undergoing high-risk procedures." What they heard was,
"I don't care about you, so I make up rules that compromise your safety."
What we soon learned was that staff members were not necessarily
looking for solutions to their fears but for acknowledgement of them.
https://www.statnews.com/2020/12/09/to-defeat-covid-19-we-must-acknowledge-the-fear-it-engenders/
'Nanopore' genome sequencing technology (ONT) has the potential to provide critical,
timely clues on how cases of SARS-CoV-2 infection are linked.
Despite elevated error rates observed in ONT sequencing reads,
highly accurate consensus-level sequence determination was achieved,
with single nucleotide variants detected at >99% sensitivity and >99% precision
above a minimum ~60-fold coverage depth,
thereby ensuring suitability for SARS-CoV-2 genome analysis. (8 pages)
https://www.nature.com/articles/s41467-020-20075-6.pdf
While the risk of SARS-Cov-2 infection was the same for women and men,
men with COVID-19 are three times more likely to require intensive care than women.
Women naturally produce more type I interferon proteins
that limit the abnormal immune response known as a cytokine storm,
believed to play a role in provoking severe forms of COVID-19.
The "female" oestradiol hormone may also help women
to fend off grave forms of the virus, as it boosts the response of T cells
- which kill infected cells- and increases the production of antibodies.
"In contrast, the male sex hormone testosterone suppresses the immune system" (10 pages)
COVID-19 and graft-versus-host disease: a tale of two diseases (and why age matters)
SARS-CoV-2 is a vector that initially homes to pulmonary stem cells
that preferentially express the ACE2 receptor. In older individuals,
stem cell number and/or function become depleted due to pathways
independent of disease-related injury to these subpopulations.
Accordingly, pathologic targeting of stem cells already deficient
due to the aging process may have dire consequences in elderly individuals.
A hypothesis is herein advanced that, as with acute graft-versus-host disease,
lung stem cell targeting is a potential co-factor
in explaining age-related severity of COVID-19 infection. (6 pages)
A virtual screening of the DrugBank database has identified a variety of
as yet unexplored ways to attack SARS-CoV-2, even as it mutates.
A double-scoring approach appears to have succeeded in avoiding false-positives
- a common problem in virtual screening.
A key part of the study is the identification of drugs that target or bind to multiple proteins
that are essential for replication of the virus
and which are also involved in the initial stage of host-cell infection.
The study proposed one cocktail: baloxavir marboxil, natamycin and RU85053,
which targets the three viral proteins respectively,
3CL Main protease, papain-like protease and RdRp.
Also recommended for testing: tivantinib, olaparib, zoliflodacin,
golvatinib, sonidegib, regorafenib and PCO-371. (16 pages)
https://www.nature.com/articles/s41598-020-75762-7.pdf
COVID-19 and the brain (34 pages)
Using systems that can model the human brain, such as brain cells created from
induced pluripotent stem cells (iPSCs) and brain organoids,
SARS-CoV-2 is shown to largely bypass neurons and astrocytes
and primarily infects choroid plexus cells, a specialized part of the blood-brain barrier,
which controls what can enter your brain and produces cerebral spinal fluid.
Choroid plexus cells produce high levels of ACE2,
which is the receptor that SARS-CoV-2 uses to enter and infect cells.
Six-month antibody response to SARS-CoV-2 in healthcare workers
assessed by virus neutralisation and commercial assays (8 pages)
Serum samples (n=296) collected six months after disease onset
were tested using three commercial assays: the Wantai Ab assay
detecting total antibodies against the spike protein receptor binding domain,
the bioMerieux Vidas assay detecting IgG to the RBD
and the Abbott Architect assay detecting IgG to the N protein.
The positivity rate was 100% with the Wantai assay,
84.8% with the bioMerieux assay and 56.4% with the Abbott assay.
Theoretical Epidemic Laws Based on Data of COVID-19 Pandemic (26 pages)
The standard growth model of epidemic evolution fails to explain intervention measures
for mitigations of the ongoing COVID-19 pandemic.
Almost all COVID-19 evolution can be modeled by three innovative epidemic laws.
Specifically, based on the world COVID-19 data, first divide an epidemic curve into 3 phases:
an exponential growth phase, an exponential decay phase, and a constant endemic phase.
Next, integrate the growth and the decay phases into the first epidemic law
with interventions as a model parameter. This law is completely opposite to
the Richards generalized logistic function in terms of intervention measures.
Then, combine the first epidemic law with the endemic phase
to form the second epidemic law,
which makes the curve of cumulative cases increase linearly as time tends to infinity.
The third epidemic law states if an epidemic is composed of multiple epidemic waves,
the superposition principle applies.
https://en.wikipedia.org/wiki/Superposition_principle
These laws were confirmed by the COVID-19 data from 18 countries
including undeveloped, developing and developed countries.
COVID-19 survivors may develop some immunity, but still should get the vaccine.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases,
has said he thinks that COVID-19 survivors should still get vaccinated.
One reason scientists have feared that natural protection from COVID-19 might be short-lived
is that immunity to milder coronaviruses that cause colds is fleeting.
Local doctors - and pharmacies - will still decide who gets COVID-19 vaccines
For phase 1a, what about when the radiologist, who works at home and reads x-rays there,
comes into the clinic and says, "Give me the vaccine. I'm a doctor." And you say,
"Well, you don't see patients in the hospital." And the doctor says, "I have privileges. I can."
Operation Warp Speed partnership with community pharmacies after phase 1a
Nov 12 announcement
includes e.g. Publix, Wegman which have no relevant info at their websites; few do...
Walgreens FAQ
"Check back to learn when the COVID-19 vaccine will be available at Rite Aid. "
https://www.riteaid.com/Covid-19
COVID-19 vaccines will be much less effective at preventing death and illness in 2021
if introduced into a population where the virus is raging - as is now the case in the U.S.
At the current U.S. COVID-19 rate (about 200,000 confirmed new cases per day),
for a 95% effective vaccine distributed at the expected pace in the first 6 months,
about 10 million Americans will contract the virus, and more than 160,000 would die.
In an alternate universe with a 50% effective vaccine
but U.S. infections at the early September rate (about 35,000 cases),
deaths in the next 6 months would be about 60,000.
Some math: 200,000 per day works out to about 1% of U.S. population infected per month
and about 4% average risk of infection over 4 months. If a single vaccine dose is 80% effective,
then 80% of 4% would avoid infection after 4 months vs 95% of 2%. Last I knew, 3.2% > 1.9%
How America's COVID-19 epidemic ends
Between public fatigue, holiday celebrations, and states keeping risky indoor spaces
like restaurants and bars open, U.S. COVID-19 cases could exceed 300,000 a day
Every state is now reporting more than - and usually well above - 4 cases per 100,000 people per day, a standard for out-of-control outbreaks.
But maybe as things get truly horrifying - as more hospitals start to hit capacity
and turn away patients because they simply can't do more - something will change. [pigs will fly]
6 factors that will affect how quickly vaccine gets to the public
Genetic screens identify host factors for SARS-CoV-2 and common cold coronaviruses (67 pages)
Some human molecules required for SARS-CoV-2 infection
weren't needed by the two common cold coronaviruses, and vice versa.
These findings could help explain what makes SARS-CoV-2 more deadly than the other two viruses.
Researchers found that certain genetic mutations prevented all three
coronaviruses from successfully infecting and killing the cells.
These were mutations in genes known to control the balance of two types of lipid molecules in human cells,
namely cholesterol and phosphatidylinositol phosphate (PIP).
To verify the importance of the cholesterol and PIP genes for coronavirus infection,
researchers engineered human cells that lack these genes completely and infected them with the virus.
Cells lacking the genes were protected from infection by all three coronaviruses.
Similarly, when the team used existing compounds to disrupt the balance of PIP or cholesterol,
the cells were less susceptible to infection by any of the viruses.
"If we could develop a few broader antiviral drugs that target host cells' molecules,
that would go a long way toward making us better prepared for future pandemic viruses."
Development of high-speed nanoPCR technology for point-of-care diagnosis of COVID-19
A magneto-plasmonic nanoparticle (MPN) that is comprised of
magnetic material in its core and a gold shell
that converts light energy to thermal energy.
Applying MPNs to PCR produced nanoPCR which reduces
RT-PCR thermocycling to 11 minutes from 1-2 hours
while retaining ~99% sensitivity and specificity. (11 pages)
Inovio Initiates INO-4800 COVID-19 Vaccine Dosing in Phase 2 Study Segment
The phase 2 segment will enroll 400 adult participants
at up to 17 U.S. sites to assess the vaccine's safety,
tolerability and immunogenicity as a two-dose regimen.
The Plymouth Meeting, Pa., drugmaker plans to complete enrollment by month's end.
Moderna vaccine trial volunteers' levels of antibodies
that latch on to a key SARS-CoV-2 protein peaked 1-2 weeks
after the second jab and fell only slightly in the subsequent 2.5 months.
Four months after the first jab, their blood still contained
'neutralizing' antibodies that disable the virus,
and none of the participants had experienced any serious vaccine-related side effects.
https://www.nejm.org/doi/10.1056/NEJMc2032195
Editorial: Rapid and frequent testing
Technology is coming online to rapidly detect COVID-19 infectiousness
in pre-symptomatic cases, which is key to managing spread.
Some California hospitals are close to reaching their breaking point,
prompting Gov. Gavin Newsom to bring in hundreds of hospital staff from outside the state
and to prepare to re-start emergency hospitals that were created
but barely used when COVID-19 surged last spring.
CA has seen a roughly 70% increase in ICU admissions in just two weeks,
leaving just 1,700 of the state's 7,800 ICU beds available.
Fractional SIR epidemiological model (15 pages)
"Standard epidemiological models rely on the presumption of strong mixing between infected
and non-infected individuals, with widespread contact between members of those groups.
We stress, rather, that transmission occurs in geographically concentrated cells.
Therefore, in our view, the use of fractional exponents helps us
more accurately predict rates of infection and disease spread."
FDA EUA for Quest at-home test collecting COVID-19, influenza A and B mail-in sample
"With just one swab or sample, combination tests that are authorized for use with home-collected samples
can be used to get answers to Americans faster, in the comfort and relative safety of their home,
which allows patients to continue to quarantine while awaiting results."
Interferon-induced transmembrane proteins (IFITMs)
are known to restrict infections by many viruses that enter cells through endocytosis,
and, conversely, enhance entry of virus at the cell surface.
" there are people who have mutations in the IFITM3 gene,
possibly making them more susceptible not only to influenza but also SARS-CoV-2"
.. which "can actually hijack IFITM3 for its own benefit to enhance entry into cells" (29 pages)
https://www.embopress.org/doi/epdf/10.15252/embj.2020106501
3 existing antihistamine drugs show effectiveness against COVID-19 virus in cell testing
"The fact that these drugs actually inhibit the virus in the lab
does not necessarily mean that they will inhibit it actively in people - but they might"
Hydroxyzine, diphenhydramine and azelastine showed direct,
statistically significant antiviral effects on SARS-CoV-2 (25 pages)
For many people, surviving COVID-19 doesn't mean getting better: "long haulers"
87% of patients who were discharged from the hospital after recovery
still had at least one symptom two months later.
35% of people surveyed who tested positive for the coronavirus and experienced symptoms,
but were not hospitalized, had not returned to their usual health after two or three weeks.
Meeting the challenge of long COVID (1 page)
Centers for the treatment of patients with long COVID
that provide care spanning multiple medical specialties are now springing up.
Using the same PCR technology on the same nasal swab samples
and analyzing completely different molecules
- from persons infected, rather than from the virus that infects them -
detects a distinct pattern of immune gene expression in infected individuals,
reducing false COVID-19 test results.
https://medicalxpress.com/news/2020-12-covid-approach-patients-immune-response.html
Is it safe to have more than one type of COVID vaccine?
A booster vaccination enhances the quality of the immune response and sends a reminder about the virus.
It doesn't matter if the vaccine used to prime the immune system is different from the one used to boost,
as long as they both contain the critical viral protein.
The risk of getting COVID and its awful and often long-term side-effects
outweigh any theoretical risk of a vaccine.
CDC: People who have gotten sick with COVID-19 may still benefit from getting vaccinated
Due to the severe health risks associated with COVID-19
and the fact that re-infection with COVID-19 is possible, people may be advised
to get a COVID-19 vaccine even if they have been sick with COVID-19 before.
At this time, experts do not know how long someone is protected from getting sick again after recovering from COVID-19.
Immunity acquired from an infection (natural immunity) varies among cases and patients.
Some early evidence suggests natural immunity may not last very long.
We won't know how long immunity produced by vaccination lasts
until we have a vaccine and more data on how well it works.
Bloomberg: Operation Warp Speed SNAFU
Practice shipments of empty vaccine containers and mock supply kits
identified hiccups in distribution. Some states didn't receive the kits at all.
Pfizer, Moderna and J&J execs say an FDA vaccine go-ahead is far from the finish line
The unprecedented speed at which Moderna, Pfizer and Johnson & Johnson
developed their shots would not have been possible without the willingness of governments
to invest in unproven products, which hastened manufacturing work
and took some of the financial risk off the companies.
First COVID-19 vaccine shipments will fall short
The CDC's Advisory Committee on Immunization Practices recommended that
the first batch of Americans to get vaccinated should be health care personnel
and residents of long term care facilities such as nursing homes.
Together, they add up to about 24 million people.
Pfizer is expected to have only 6.4 million doses of vaccine ready by mid-December.
California has 2.4 million healthcare workers, and Governor Newsom said earlier this week
that the state is only receiving 327,000 doses of the vaccine from Pfizer to start with..
NY Governor Andrew Cuomo said his state will receive 170,000 doses of Pfizer's vaccine on December 15th.
The state's highest priority groups include 85,000 nursing-home residents
and 130,000 nursing home facility workers. Texas expects to end up with 1.4 million doses
when combining shipments from Pfizer and Moderna by the end of December,
intended for an estimated 1.6 million health care workers.
Differential effects of intervention timing on COVID-19 spread in the U.S. (10 pages)
Nonpharmaceutical interventions (NPIs) have successfully limited COVID-19 spread
in some other countries. This study attempts to quantify U.S. NPI effectiveness by
adapting and applying a dynamic metapopulation model informed by human mobility data
and representing SARS-CoV-2 transmission in 3142 U.S. counties 21 Feb - 3 May, 2020.
Counterfactual simulations are based on what might have been. In this study,
initial infection seedings and NPI timings were tweaked to adjust their model results to better
match collected statistics. With compliance arguably an independent random variable,
this study is IMO problematic.
New Mexico hospitals overwhelmed, rationing treatment
Several lines of evidence are now sending us the same message:
Hospitals are becoming overwhelmed, causing them to restrict admissions
and leading to more U.S. deaths.
COVID-19 ultra-rapid breath test clinical trials
U.S.-based Canary Health Technologies (Canary) and DIVOC Laboratories (Divoc),
a Delhi-based laboratory certified by the National Accreditation Board for Testing
and Calibration Laboratories (NABL), will collaborate on a clinical trial in Delhi
to develop an ultra-rapid and highly accurate breath test for COVID-19.
Preliminary results from 750 subjects are expected before the end of December,
with an aim to be in the market early 2021.
U.S. and European trials are also being planned and due to start before the end of 2020.
The FDA might have saved time reviewing Pfizer's vaccine EUA application
if it evaluated data on the vaccines on a rolling basis,
instead of getting all of the information, tens of thousands of pages, at once.
(Regulators in the U.K. accepted Pfizer's data on a rolling basis,
but the FDA argues that the processes were simply very different.)
A Stochastic Compartmental Model for COVID-19 (37 pages)
The SIS-model (Susceptible => Infectious => Susceptible) in presence of
lockdown measures and integrated with the action of hospitals and health Institutes
is able to contain and dampen the SARS-CoV-2 epidemic spread.
[ this implicitly assumes hospital capacity is not exceeded,
although that may involve more dying elsewhere ]
A holistic approach for suppression of COVID-19 spread in workplaces and universities
Under the modeling assumptions, maintaining a prevalence below 3% can be achieved
in an office setting by testing its workforce every two weeks,
whereas achieving this same goal for a university could require as much as
fourfold more testing (i.e., testing the entire campus population twice a week).
(31 pages)
Galectin antagonist use in mild cases of SARS-CoV-2 cases;
pilot feasibility randomised, open label, controlled trial (21 pages)
Prolectin-M was administered as a multi dose regime of 4gm tablets, each
containing 2 grams of (1-6)-Alpha-D-mannopyranosil mixed with 2 grams of dietary fibre.
Each participant took a single chewable tablet every hour, to a maximum of 10 hours daily.
Tablets were administered only during the day, for a total of 5 days.
Among 10 randomized participants, 3 of 5 receiving Prolectin-M turned rRT-PCR negative
by day 7, compared to none in the control group. 4 of 5 in each group were female.
All five participants in the treatment group demonstrated a rapid drop by day 3
in copies/uL of Nucleocapsid protein gene. 2 subjects in each arm still tested positive on day 14.
New CRISPR-based test for COVID-19 uses a smartphone camera
All CRISPR diagnostics to date have required that the viral RNA be converted to DNA
and amplified before it can be detected, adding time and complexity.
In contrast, the novel approach described in this recent study
skips all the conversion and amplification steps,
using CRISPR to directly detect the viral RNA.
THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19:
A SYSTEMATIC REVIEW OF MECHANISMS AND EVIDENCE (17 pages)
Mounting evidence suggests that ivermectin may be an important drug
in the fight against COVID-19.
Eight studies had released results at the time of writing this review and met inclusion criteria.
A statistically significant association between reduced mortality and ivermectin use
was observed (p= 0.03). This was even more pronounced in the subset severe patients,
with a mortality of 80.7% in controls vs 38.8% in the ivermectin group.
Why the AstraZeneca-Oxford COVID-19 vaccine is different
In the UK trial group, AZD1222 was given as a half dose,
followed by a full dose around one month later, resulting in 90% efficacy.
Brazil participants were given two full doses at least one month apart,
and the efficacy was 62%.
Three-step guide to COVID-19 personal risk minimization,
based on "NY Times" survey of 700 epidemiologists
1. Eliminate, without exception, spending time in a confined space (outside your household)
where anyone is unmasked.
2. Avoid spending extended time in indoor spaces, even with universal masking.
3. Think about a personal risk budget
How 700 Epidemiologists Are Living Now, and What They Think Is Next
90% Went on errands, such as to the grocery store or pharmacy
72% Brought in mail without precautions
62% Hiked or gathered outdoors with friends
44% Saw a doctor for a nonurgent appointment
McQ - An open-source multiplexed SARS-CoV-2 quantification platform (44 pages)
McQ is based on the parallel sequencing of barcoded amplicons
generated from SARS-CoV-2 genomic RNA. McQ uses indexed,
target- specific reverse transcription (RT) to generate barcoded cDNA
for amplifying viral- and human-specific regions. The barcoding system
enables early sample pooling to reduce hands-on time
and makes the approach scalable to thousands of samples per sequencing run.
Homemade reverse transcriptase and polymerase enzymes and non-proprietary buffers
reduce RNA to library reagent costs to ~92 cents/sample
and circumvent potential supply chain shortages. McQ analytical sensitivity
is lower than with gold standard RT-qPCR based tests at 50 copies/ul,
corresponding to samples with a Ct of approximately 30.
It's likely that the apparently protective effects of 17B-estradiol,
a naturally occurring, abundant female hormone, relate to a key property of this molecule:
it attenuates the so-called "cytokine storm" that's thought to underlie much of the cellular-scale
and organ/tissue-level damage wrought by a SARS-CoV-2 infection,
via dysregulation of a patient's immune response.
https://medicalxpress.com/news/2020-12-age-gender-covid-complex-hormone-driven.html
Comparative host-coronavirus protein interaction networks
reveal pan-viral disease mechanisms (28 pages)
Common host pathways among MERS-CoV, SARS-CoV-1 and SARS-CoV-2 were identified
by expressing viral proteins in human cells, using mass spectrometry
to identify human host proteins that are physically associated with each viral protein,
and looking for conserved interactions across all three viruses.
Genetic screening identified host factors that either enhanced or inhibited viral infection.
To connect their in vitro molecular data to clinical information for COVID-19 patients,
authors evaluated medical billing data on nearly 740,000 patients in the U.S. with documented SARS-CoV-2 infection.
In this cohort, they studied the use of drugs against selected targets identified in their study,
asking whether patients who received them fared better than controls
treated with clinically similar drugs that do not act on coronavirus host factors.
Patients that received drugs focused against certain selected targets fared better in some cases.
This represents an example of how molecular insight
can rapidly generate testable clinical hypotheses
and help prioritize candidates for prospective clinical trials
or future drug development.
De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
This updates a 20 Aug paper. The SARS-CoV-2 "spike"
is known to bind with Angiotensin-converting enzyme 2 (ACE2),
an enzyme attached to membranes of cells in lungs, arteries,
hearts, kidneys and intestines. This paper reports progress
on developing decoys that preferentially bind to that spike.
While a design with 3 binding sites is wanted
for robustness against potential virus mutations,
an alternative with 2 sites demonstrates 10x binding.
Moderna mRNA-1273 vaccine confers at least 3 months immunity: study
"The amount of vaccine-produced antibodies was higher in younger patients
than in older patients, but reasonably strong immune responses were still seen
even in patients up to 70 years of age."
Model for evaluating cost-effectiveness of surveillance testing for SARS-CoV2 (15 pages)
This NIH model assumes that people with COVID-19 are infectious
for an average of 15 days and are equally infectious on each of these days.
For current rates of spread, cost-effectiveness usually requires
a value per life saved greater than $100,000 and
depends critically on the extent and frequency of testing.
Robust neutralizing antibodies to SARS-CoV-2 infection persist for [5] months (5 pages)
On the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System
in New York City, the vast majority of infected individuals with mild-to-moderate COVID-19
experience robust immunoglobulin G antibody responses against the viral spike protein.
Titers are relatively stable for at least a period of about 5 months,
and anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2.
Researchers found one mutation that caused SARS-CoV-2 to escape recognition by Regeneron's monoclonal antibody cocktail,
and a few others that helped it to escape one of the three antibodies.
One mutation is prevalent in Europe,
and another has been detected in the Netherlands and Denmark,
where it has been found in SARS-CoV-2 samples
taken from mink and people working at mink farms.
https://www.nature.com/articles/d41586-020-00502-w
1) If a vaccine candidate is found to be safe and efficacious in a placebo-controlled trial,
should the researchers continue that trial as designed?
(authors say "yes", so long as that trial is relatively short and proven vaccine is scarce)
2) Should researchers continue to test other vaccine candidates using placebo-controlled trials?
"researchers should consider whether their trials can be redesigned as a comparison
between the vaccine candidate they are testing and a safe and efficacious vaccine."
(5 pages)
https://science.sciencemag.org/content/early/2020/12/02/science.abf5084.full.pdf
Metformin reduced COVID-19 death risks in women
Metformin is an established, generic medication for managing blood sugar levels
in patients with type 2 diabetes.
It also reduces inflammation proteins like TNF-alpha that appear to make COVID-19 worse.
Untuned antiviral immunity in COVID-19
revealed by temporal type I/III interferon patterns and flu comparison (25 pages)
A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses
precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage.
This paradigm does not apply for COVID-19; in 32 moderate-to-severe patients,
IFN-? and type I IFN production were both diminished and delayed,
induced only in a fraction of patients as they became critically ill. On the contrary,
pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6
and IL-8 were produced before IFNs in all patients and persisted for a prolonged time.
Re: COVID-19 Indoor Safety Guideline (Nov 30 blog)
https://indoor-covid-safety.herokuapp.com/
Cranking risk tolerance down to 0.01 and assuming most masks are coarse and poorly fitted
(Mask Fit/Compliance < 25%), is more credible (to me), but seemingly supposes
starting with clean air (empty room), not Walmart near the end of a busy day.
"well-mixed indoor air" is a major cop-out;
it applies to empty rooms, where one can literally feel drafts everywhere.
Remember all the places where one used to see cigarette smoke hanging in the air?
New COVID-19 surveillance predicts direction, speed and acceleration of virus
Northwestern University is hosting a dashboard for the new COVID tracking system
- open to anyone - with the new metrics as well as traditional metrics.
[ GASSP seemingly not yet online ]
The new system and the first U.S. surveillance report will be published
in the Journal of Medical Internet Research https://www.jmir.org/ on Dec. 3.
Comparison of coronavirus antibody tests revealed too optimistic claims
The study involved 97 patients with confirmed COVID-19 and 9 tests.
In half of the patients, all nine antibody tests gave a positive result.
In two patients, none of the tests detected coronavirus antibodies.
"In the everyday work of Synlab,
we are using the Abbott test that is sensitive to antibodies to the nucleocapsid.
If that gives a borderline negative result in a patient, we will analyze this sample again
using another test sensitive to antibodies to the spike protein."
Animals susceptible to SARS-CoV2 have a few things in common.
Humans, cats, and dogs have two cysteine amino acids that form a special disulfide bond
held together by an oxidizing cellular environment.
This disulfide bond creates an anchor for the virus.
"Antioxidants could decrease the severity of COVID-19 by interfering with entry of the virus
into host cells and its survival afterwards in establishing further infection"
Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2
in large clinical sample cohorts (13 pages)
A high-throughput targeted proteomics assay detects SARS-CoV-2 nucleoprotein peptides
directly from nasopharyngeal and oropharyngeal swabs. A modified magnetic particle-based
proteomics approach implemented on a robotic liquid handler
enables fully automated preparation of 96 samples within 4 hours.
A TFC-MS system allows multiplexed analysis of 4 samples within 10 min,
enabling the processing of more than 500 samples per day.
Validated using 985 specimens previously analyzed by real-time RT-PCR
to detect up to 84% of the positive cases with up to 97% specificity
Two more alternative COVID-19 vaccine strategies
Unlike AstraZeneca's Oxford University-partnered AZD1222,
which uses a monkey adenovirus to perform the delivery task,
the City of Hope shot (COH04S1) adopts Modified Vaccinia Ankara (MVA),
which is an attenuated poxvirus that's also frequently used as a viral vector for vaccines.
It is hoped to induce more durable immunity and is in a phase 1 clinical trial.
The German Center for Infection Research has also launched a phase 1 trial for its MVA vaccine candidate, MVA-SARS-2-S.
Biovaxys' BVX-0320 vacccine candidate, based on a concept known as haptenization, is still
pending animal study results before requesting regulatory consent for a phase 1 clinical trial.
Prediction of COVID-19 spreading and optimal coordination of counter-measures:
from microscopic to macroscopic models to Pareto fronts (34 pages)
The goal is a model that allows for optimal compromises between the conflicting objectives.
Accurate and easily computable prediction schemes for all possible combinations of countermeasures
are required for approximating the Pareto set via available techniques for multiobjective optimization.
This [well-written, IMO] paper reports on
an agent-based mobility model for Berlin that is computationally very expensive.
That model is approximated by a macro-model based on differential equations.
Computing Pareto sets of countermeasures combinations
that form optimal compromises between the conflicting objectives is demonstrated.
Effect of Vitamin D deficiency on COVID-19 status: A systematic review (21 pages)
Vitamin D may serve as a mitigating effect for COVID-19 infection, severity and mortality.
Encourage people to eat foods rich in vitamin D such as fish, red meat, liver
and egg yolks while at the same time providing vitamin D supplements for COVID-19 patients
in order to boost their immune systems.
An evidence-based online COVID-19 risk calculator (5 pages)
https://marc-artzrouni.shinyapps.io/ArtzCovidRisk/
Includes clear descriptions for INPUTS, MODEL, FAQ
Based on 5 input parameters for a setting (party, store, stadium, etc.), it calculates:
1. Your individual chance of getting infected (probability of transmission)
during a contact with an infected person in the group.
2. Your overall chance of infection during the event.
3. The expected number of new infections
if all members in the group mingle in the same way you do
COVID-19 Trends in Florida K-12 Schools, August 10 - November 14, 2020 (8 pages)
COVID-19 cases reported in Florida schools were most influenced by community case rates,
district mask policies, and percent of students attending face-to-face.
Student case rates in high schools (12.5 per 1,000) were 70% higher than younger cohorts.
Staff rates are higher than student rates in all school environments except high schools.
Student case rates nearly tripled in the period October 3 - November 14
compared to the period August 10 - October 3.
Only 2 of Florida's 67 counties had school case rates lower than community case rates.
Researchers at the University of Sao Paulo, Brazil have demonstrated for the first time that
an immune mechanism, inflammasome, participates in activation of the inflammatory process
in COVID-19 patients that can damage several organs and even lead to death.
"Drugs already approved for human use are capable of inhibiting inflammasome activation"
https://medicalxpress.com/news/2020-12-immune-mechanism-triggers-cytokine-storm.html
A Healthy Buildings Guideline for the COVID-19 Pandemic and Beyond (13 pages)
Cloth masks have estimated 30-50% efficiency, compared to 90% for real masks.
For table 6 and 7, higher risk situations require populations with lower susceptible fraction.
OD is pre-pandemic occupation density. Table 4 assumed an 8 day infectious period.
Criterion threshold refers to airborne virus removal.
A two-arm, randomized, controlled, multi-centric, open-label Phase-2 study
to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.
[ 36 patients 2:1 treated vs placebo; Itolizumab was generally safe and well tolerated,
with encouraging results ] (41 pages)
Rapid and accurate point-of-care testing for SARS-CoV2 antibodies ( 29 pages )
[ As with many of these evaluations, specificity and sensitivity are based on
seemingly small populations (169 in this case), but results here are impressive ]
Cost-effective serologic test based on antibody-dependent agglutination of antigen-coated latex
particles, which uses ~5 ul plasma and takes <5 min to complete with no instrument required.
Antibodies against the receptor-binding domain of the spike (S-RBD)
or the nucleocapsid (N) protein of SARS-CoV-2 were detected with 100% specificity and ~98% sensitivity.
>92% of patients had detectable antibodies on the day of positive viral RNA test,
suggesting that seroconversion may occur earlier than previously thought
and that the agglutination antibody test may complement RNA testing for POC diagnosis of SARS-CoV-2 infection.
A Net Benefit Approach for the Optimal Allocation of a COVID-19 Vaccine ( 35 pages )
In a scenario with a sterilizing vaccine that is 80% effective,
a stockpile sufficient for 40% population coverage,
and prioritisation of those over the age of 60 at high risk of poor outcomes,
active cases are reduced by 29.2% and net monetary benefit increased
by $297 million dollars, relative to an identical scenario with no vaccine.
[ This report did not consider prioritizing those likely to provoke super-spreader events,
who would (IMO) practically be difficult to identify. It attempts to distinguish age
from high risk of poor outcomes, which also seems (IMO) doomed. Nice graphs ]
COVID-19 Risk Assessment Model (CRAM), a transmission dynamic ordinary differential
equation compartmental susceptible-exposed-infected-recovered (SEIR) mode
was programmed in Wolfram Mathematica, version 12.1.
The relative impact of prioritisation strategies varies greatly
depending on concurrent public health interventions,
e.g. policies such as school closures and senior contact reductions
have similar impacts on incremental net monetary benefit
when there is no prioritisation given to any age or risk group (147 vs. 120 million, respectively),
but when older and high risk groups are given priority, the benefit of school closures is
much larger than reducing contacts for seniors (iNB 122 vs. 79 million, respectively).
COVID-19 risk evaluation and testing strategies
based on contact tracing network and information analysis (9 pages)
This study proposes strategic selection of the right individuals for testing
and extracting far more information from the minimum samples.
[ IMO, utterly impractical ]
Risk assessment for airborne disease transmission by poly-pathogen aerosols (63 pages)
[ warning: VERY heavy reading, e.g.: "There is an analytical solution to Eq (45),
though it is not closed form unless the time dependence of a, B, and ? allow it."
Some complexity hinges on so-called "multiplicity":
"We will use the term multiplicity to refer to the number of pathogen copies in an aerosol."
"Ignoring multiplicity causes the infection risk to be overestimated
even though the expected average pathogen dose does not change."
To make sense of charts at the end requires noting on page 24/37:
"...at t = 3 hr, one more infectious individual enters the room who is continuously coughing
while wearing a simple2 mask, breathing at a higher rate of ^I,j = 2.0 m3 hr-1,
and has a higher respiratory tract fluid pathogen concentration of pp,j = 1011 cm-3
at the very upper range for SARS-CoV-2." ]
Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses
to SARS-CoV-2 in mild or moderate non-hospitalised patients (25 pages)
SARS-CoV-2 frequently results in mild or moderate disease with potentially
lower concentrations of antibodies compared to those that are hospitalised.
Here, an ELISA is validated using SARS-CoV-2 trimeric spike glycoprotein,
with targeted detection of IgG, IgA and IgM (IgGAM) using serum and
dried blood spots (DBS) from adults with mild or moderate disease.
The assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate
COVID-19 samples, >14 days post symptom onset and 624 COVID-19 negative samples.
It was validated using 73 PCR-confirmed non-hospitalised COVID-19
and 359 COVID-19 negative serum samples with an additional 81 DBSs,
and further validated in 226 PCR-confirmed non-hospitalised COVID-19
and 426 COVID-19 negative clinical samples.
98.6% sensitivity (95% CI, 92.6-100.0) and 98.3% specificity (95% CI, 96.4-99.4) were estimated.
A COVID-19 transmission model informing medication development and supply chain needs (30 pages)
This is claimed to be the first model "t to clearly quantify the effect of NPIs
(non-pharma interventions) on COVID-19 transmission in individual countries
while also accounting for the expected contribution of asymptomatic cases
to COVID-19 transmission and differentiating potential super-spreaders."
Using Johns Hopkins data, this model estimated 65.8% of cases as asymptomatic;
symptomatic and asymptomatic people were estimated to infect 2.12 and 5.83 other people,
respectively. An estimated 9.55% of cases were super-spreaders
with a 2.11-fold higher transmission rate than average.
[ country-specific fudge factors were allowed; U.S. was modeled, but NOT projected ]
Ethnicity, Household Composition and COVID-19 Mortality: A (UK) National Linked Data Study (22 pages)
Older adults living with younger people are at increased risk of COVID-19 mortality;
living in a multi-generational household explained between 10% and 15% of elevated risk
of COVID-19 death among older females from South Asian background,
but very little for South Asian males or people in other ethnic minority groups.
The COVID-19 vaccines are a marvel of science. Here's how we can make the best use of them
"There's tremendous pressure to get the vaccine out and then administered in 24 hours"
Some experts worry the artificial deadline could lead to a botched rollout.
The Association of Immunization Managers and ASTHO (Association of State and Territorial Health Officers)
have been pleading with Congress for money to do the work
on the ground to get people vaccinated. They argue states need $8.4 billion to recruit
and train extra workers, to run local advertising, to beef up software programs
that are not currently up to the task. So far, they've received $340 million.
Vaccine rollout
Long-term care residents, who have suffered a terrible toll in the pandemic,
are a more recent addition to Phase 1a, as the first group is called. As of Nov. 26,
there have been 730,000 COVID-19 cases in this population, and 100,240 deaths.
While COVID-19 vaccines have not yet been tested in long-term care residents,
they have been tested in some older adults in clinical trials.
These volunteers reported fewer side effects after vaccination,
raising questions about how strong an immune response the vaccines are inducing.
States need further guidance on how to sub-prioritize vaccination during Phase 1a,
because there will not be sufficient supplies initially to vaccinate all health providers at once.
Vaccinating all health care providers at once might not be advisable;
these vaccines are "reactogenic", often inducing fatigue, sore arms, sometimes even fever.
Hospitals might want to vaccinate departments or clinics in a couple of waves,
so that all staff aren't dealing with these side effects at once.
How nanotechnology helps mRNA COVID-19 vaccines work
Lipid nanoparticles are the fatty molecular envelopes that help strands of mRNA
- the genetic messenger for making DNA code into proteins -
evade the body's biological gatekeepers and reach their target cell without being degraded.
Vaccines are happening, but first: coming months "are going to be just horrible."
The U.S. may well become the first country to bring the virus to heel through pharmaceutical prowess,
but having created many nursing home vacancies. Various studies, involving machines puffing fine mists,
have shown that high-quality masks can significantly reduce the spread of pathogens between people in conversation,
but no concerted effort has been made to drastically increase N95 mask availability.
https://www.nytimes.com/2020/11/30/health/coronavirus-vaccines-treatments.html
Rapid COVID-19 tests can be useful "but there are far too few to put a dent in the pandemic
Anecdotally, these tests seem to miss recent, mild and asymptomatic infections"
in fact, rapid tests are authorized by the U.S. CDC only for use in symptomatic COVID-19 patients.
Researchers have estimated that the U.S. would need to perform
at least 20 million rapid tests per day to drive down infections.
Virologists at the Rega Institute at KU Leuven (Belgium) have developed
a vaccine candidate against COVID-19 based on the yellow fever vaccine,
which also still works against yellow fever.
Tested in mice and monkeys; clinical trial preparations have begun.
RegaVax works after one dose, unlike many of the front-runners in the race today.
https://medicalxpress.com/news/2020-12-vaccine-candidate-covid-yellow-fever.html
An international expert consensus has been published
on three points of contention to better facilitate patient treatment amid the pandemic:
personal protection equipment (PPE), the use of high-flow nasal oxygen,
and when tracheal intubation is best performed.
https://medicalxpress.com/news/2020-12-guidance-properly-covid-patient-airways.html
Rational development of a human antibody cocktail
that deploys multiple functions to confer Pan-SARS-CoVs protection (12 pages)
Cryo-EM studies produced high-resolution structure of the SARS-CoV-2 spike
in complex with neutralizing antibodies H014 and P17,
together with functional investigations revealed that in a two-antibody cocktail,
synergistic neutralization was achieved by S1 shielding and conformational locking,
thereby blocking receptor attachment and viral membrane fusion,
conferring high potency as well as robustness against viral mutation escape.
Furthermore, cluster analysis identified a hypothetical 3rd antibody partner
for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
Novavax said it will begin a delayed phase 3 trial in the U.S. and Mexico
to evaluate its COVID-19 vaccine candidate, NVX-CoV2373, "in the coming weeks"
and that its 15,000-person late-stage trial in the UK is now fully enrolled.
The company originally anticipated a mid-October start date
for the North American trial but hit delays in securing enough vaccine doses.
https://ir.novavax.com/node/15321/pdf
Nanoengineers at the University of California San Diego have developed new and improved probes,
known as positive controls, made from virus-like particles that could make it easier
to validate rapid, point-of-care diagnostic tests for COVID-19 across the globe.
Positive controls that are primarily used to validate today's COVID-19 tests
are naked synthetic RNAs, plasmids or RNA samples from infected patients,
but RNA and plasmids are not stable like viral particles.
https://phys.org/news/2020-12-virus-like-probes-rapid-covid-accurate.html
CDC researchers found SARS-CoV-2 antibodies in 39 Red Cross blood samples
from California, Oregon, and Washington as early as Dec. 13 to Dec. 16.
They also discovered antibodies in 67 samples from Connecticut, Iowa,
Massachusetts, Michigan, Rhode Island, and Wisconsin in early January.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1785/6012472
Washington Post food critic's descent into COVID-19
" just 24 hours into this nightmare, I woke up around 4 a.m., feeling generally uncomfortable.
I sat up in bed, and within a matter of minutes, I could feel my body start to turn against me.
I felt warm, so I slid to the floor to let the hardwoods cool my skin. That's when I experienced
a pain so profound and all-encompassing I couldn't put it into words"
https://www.washingtonpost.com/food/2020/11/29/food-writer-covid/
A model for estimating indoor COVID-19 safety scenarios.
Website loaded very slowly for me:
https://indoor-covid-safety.herokuapp.com/
Thanksgiving dinner in a 20-foot-by-20-foot dining room
with a group of 10 people, only one with COVID-19, would be "safe" for 18 minutes.
An 180,000-square-foot Walmart with 1,000 young healthy people all wearing coarse cotton masks
properly would be safe for 68 minutes if only one person has COVID-19.
A 30'x30' room with 12' ceilings and normal HVAC
would be "safe" for 10 elderly folks in typical masks up to 21 minutes.
Of 152 COVID-19 patients with mild symptoms
none of 80 treated with fluvoxamine deteriorated,
while 6 of 72 give placebo worsened.
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) for treating depression,
but also activates a protein that inhibits production of cytokines.
https://medicalxpress.com/news/2020-11-antidepressant-covid-.html
Cepheid's Xpert Xpress SARS-CoV-2/flu/respiratory syncytial virus (RSV)
rapid molecular diagnostic test has received CE mark certification and FDA EUA.
A single sample can detect COVID-19, influenza A/B and/or RSV infections in about 36 minutes.
The GeneXpert System can process up to 80 samples at a time for about 2000 daily.
A psychrometric model to predict the biological decay
of the SARS-CoV-2 virus in aerosols (16 pages)
The principal finding of our study is that
the biological decay constant, k, for the SARCoV-2 virus in aerosols
can be predicted with reasonable accuracy using a linear regression model
with the variables: enthalpy (heat + pressure*volume), specific volume (air volume/mass)
and vapor pressure (or absolute humidity) as predictors.
How effective are the COVID-19 vaccines? A Bayesian analysis (7 pages)
The estimated effectiveness for the Pfizer vaccine is 89-97% and for Moderna 86-97%.
The analysis casts some doubts on whether the half+full dose regime
of the AstraZeneca COVID-19 vaccine is (much) more effective (66-96%)
than the 2x full dose regime (37-74%).
The impact of vaccination on COVID-19 outbreaks in the U.S. (14 pages)
Assumptions:
Healthcare workers and high-risk individuals were prioritized for vaccination,
while children under 18 years of age were not vaccinated.
Vaccine efficacy of 90% against infection following 2 doses administered
28 days apart achieving 40% vaccine coverage of the overall population.
10% pre-existing population immunity for the base-case scenario and calibrated to an
effective reproduction number of 1.5, accounting for current U.S. COVID-19 interventions.
Prediction:
Overall attack rate reduced to 1.6% (95% CI: 1.3% - 1.8%) from 7.1% (95% CI: 6.3% - 7.9%)
Highest relative reduction (83-90%) was observed among individuals aged 65 and older.
Vaccination reduced adverse outcomes by more than 80%:
non-ICU: 85.2% (95% CI: 82.3% - 87.6%),
ICU hospitalizations: 85.3% (95% CI: 82.3% - 87.8%),
deaths: 87.8% (95% CI: 85.1% - 90.1%)
Dietary supplements during the COVID-19 pandemic (24 pages)
In an analysis including 327,720 UK participants, the use of probiotics, omega-3 fatty acids,
multivitamins or vitamin D was associated with a lower risk of SARS-CoV-2 infection
by 14%(95%CI: [8%,19%]), 12%(95%CI: [8%,16%]), 13%(95%CI: [10%,16%]) and 9%(95%CI: [6%,12%]),
respectively, after adjusting for potential confounders.
No effect was observed for vitamin C, zinc or garlic supplements.
The protective associations for probiotics, omega-3 fatty acids,
multivitamins and vitamin D were observed in females across all ages and BMI groups,
but were not seen in men.
Quantifying superspreading for COVID-19 using Poisson mixture distributions (19 pages)
When individual variation in disease transmission is present, as for COVID-19,
secondary case count is often modelled using a negative binomial distribution.
Revisiting 3 previously analysed COVID-19 datasets and quantifying the proportion
of cases responsible for 80% of transmission, the number of secondary cases
for these datasets is better described by a Poisson-lognormal distribution.
Universities and COVID-19 Growth at the Start of the 2020 Academic Year (36 pages)
markedly increased case growth in counties with large universities (20,000+ students)
at the start of the fall 2020 semester. A survey of 500 colleges and universities found that
only 27% of universities performed re-entry testing before the start of the semester,
and only 20% of universities have committed to routinely test their populations.
[ much hand-wringing, little useful data ]
91,635 U.S. COVID-19 patients hospitalized Saturday, most ever
'A natural disaster ... in all 50 states at the same time' is unfolding
just as travelers disperse nationwide after Thanksgiving.
New cases now mean new hospitalizations by Christmas.
"There's no way that the hospitals can be fully prepared for what we're currently facing"
https://www.cnn.com/2020/11/29/health/us-coronavirus-sunday
COVID-19 Growth in Rural versus Urban Counties with Major Universities
at the Start of the 2020 Academic Year (13 pages)
Small metro and non-metro counties with universities had a dramatic infection spike
near the beginning of the semester and infection growth remained significantly higher
than their large and medium metro counterparts for the duration of the study.
[ This would be an obvious time for Trump misadministration to pull off whoppers;
most U.S. news websites appear to be on autopilot today..
That freed up time to slog thru more unappetizing papers. ]
Type O blood linked to lower COVID risk;
low vitamin D levels increase risk, but high vitamin D levels do not reduce it.
COVID-19 "cytokine storm" is specifically TNF-alpha and IFN-gamma panoptosis.
80% of COVID-19 survivors discharged from hospitals need help walking, dressing, and bathing.
https://www.reuters.com/article/us-health-coronavirus-science-idUSKBN2872LH
Los Angeles County under lockdown order Nov 30-Dec 20, with religious exemption;
'rounding the corner into a calamity,' U.S. FAA supports first mass COVID-19 vaccine shipment;
CDC's Advisory Committee on Immunization Practices emergency meeting on Tuesday,
unusually ahead of anticipated vaccine EUA. [ no pressure ]
https://www.cnn.com/2020/11/28/health/us-coronavirus-saturday/index.html
United flies first batches of Pfizer's vaccine
Vaccine doses for Europe will be produced at sites owned by BioNTech
- Pfizer's German partner - as well as in Pfizer's manufacturing site in Belgium.
In the U.S., it will be produced in Michigan, at the Kalamazoo plant.
Covering two square miles, it is Pfizer's largest manufacturing site.
Nucleocapsid protein of SARS-CoV-2 phase separates into
RNA-rich polymerase-containing condensates. [ 10 dense pages ]
The nucleocapsid protein of SARS-CoV-2 is produced at high levels within infected cells,
enhances the efficiency of viral RNA transcription, and is essential for viral replication.
Inhibition of RNA-induced phase separation of the nucleocapsid protein
by small molecules or biologics thus can interfere with a key step in the SARS-CoV-2 replication cycle.
[ So far as I could determine, no such interference was actually accomplished ]
https://www.nature.com/articles/s41467-020-19843-1
SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication.
[ AKA "all that golders is not gilt" ] (13 pages)
"The detection of subgenomic RNA is therefore not direct evidence of active infection"
https://www.nature.com/articles/s41467-020-19883-7.pdf
Unheeded SARS-CoV-2 protein? Look deep into negative-sense RNA (7 pages)
The genome of SARS-CoV-2 is one of the largest of RNA viruses,
comprising 26 known protein-coding loci.
This study found one new functional SARS-CoV-2 protein-coding loci
and suggests the existence of still undescribed SARS-CoV-2 protein,
which may play an important role in the viral lifecycle and COVID-19 pathogenesis.
https://www.biorxiv.org/content/10.1101/2020.11.27.400788v1.full.pdf
Highly functional virus-specific cellular immune response
in asymptomatic SARS-CoV-2 infection (42 pages)
Asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity;
on the contrary, they mount a robust and highly functional
virus-specific cellular immune response with increased IFN-y and IL-2 production.
https://www.biorxiv.org/content/10.1101/2020.11.25.399139v1.full.pdf
A Novel Cell Therapy for COVID-19 and Potential Future Pandemics:
Virus Induced Lymphocytes (VIL) (27 pages)
Peripheral blood mononuclear cells were obtained from 431 convalescent COVID-19 individuals,
mixed with a bunch of stuff and cultured for 7 days
to multiply virus-specific T cells by 700x.
https://www.biorxiv.org/content/10.1101/2020.11.26.400390v1.full.pdf
Modeling, post COVID-19
First part of this editorial is a throw-away, but then goes on to describe how
the U.S. should consider a pandemic infrastructure analogous to that for weather,
where the National Science Foundation (NSF) supports basic research in weather
and climate modeling, while NOAA's National Weather Service
distributes results of its operational models to weather-forecast offices.
https://science.sciencemag.org/content/370/6520/1015
The antibody cocktail REGN-COV2 provided benefits in both rhesus macaques,
which may model mild disease, and in golden hamsters,
which present more severe symptoms, when administered either
prophylactically or therapeutically and is currently in clinical trials. (7 pages)
https://science.sciencemag.org/content/sci/370/6520/1110.full-text.pdf
40 minutes of "moderate to vigorous intensity physical activity" every day
roughly balances out 10 hours of sitting still.
[ cats already knew ]
https://bjsm.bmj.com/content/54/24/1451
COVID-19 treatments: some progress, no panacea
Dexamethasone and other drugs in the same corticosteroid family can be effective
and are recommended by the WHO in severe and critical patients.
Still under investigation: Tocilizumab, Synthetic antibodies (e.g. Regeneron's)
A point-of-care test inexpensive enough to use frequently
would have sensitivity for detecting infections in time to act,
without having to meet the benchmark analytic limit of detection.
https://www.nejm.org/doi/full/10.1056/NEJMp2025631
In 14 studies of 2568 COVID-19 patients,
the incidence of recurrent SARS-CoV-2 positivity was 14.8%,
with estimated 35 days from disease onset to recurrence
and 10 days from last negative to the recurrent positive result.
Patients with younger age and a longer initial illness
were more likely to experience recurrent SARS-CoV-2 positivity.
https://www.nature.com/articles/s41598-020-77739-y
The central role of the nasal microenvironment in the transmission, modulation,
and clinical progression of SARS-CoV-2 infection. (12 pages)
Fairly readable and thorough, argues (without proof) that
nasal vaccination may work faster and better than conventional injections.
https://www.nature.com/articles/s41385-020-00359-2.pdf
COVID-19 predictability in the U.S. using Google Trends time series (12 pages)
[ Seeming, no predictions were tested ]
Statistically significant correlations were observed for the U.S. and for several U.S. states,
which is in line with previous studies that argue that there is a relationship between Google Trends and COVID-19 data.
Exploring Risks of Human Challenge Trials for COVID-19 (31 pages)
A simple 50-person dosing trial using younger individuals has
a 99.1% (95% CI: 98.8% to 99.4%) probability of no fatalities,
and a 92.8% (95% CI: 90.3% to 94.6%) probability of no cases requiring hospitalization.
video of Cuomo's holiday COVID-19 warning; U.S. mask mandate is long overdue
1) the current rate of increase already locks in a major COVID-19 spike;
a minimum 20% rate growth is predicted.
2) 37 days of holiday risk from increased social activity
https://www.youtube.com/watch?v=TKrcoVViWAM
U.S. scales back contact tracing efforts, acknowledging that
contact tracing efforts can no longer be expected to contain the virus's spread.
2 million new cases recorded in less than 2 weeks.
CDC: focus on cases less than 6 days old.
https://www.nytimes.com/live/2020/11/25/world/covid-19-coronavirus
To date, SARS-CoV-2 mutations do not appear to have increased transmissibility
Researchers have so far identified 12,706 mutations in SARS-CoV-2;
there is strong evidence that 398 have occurred repeatedly and independently.
Most common mutations appear to have been induced by the human immune system,
rather than being the result of SARS-CoV-2 adapting to its novel human host.
"The virus seems well adapted to transmission among humans,
and it may have already reached its fitness optimum in the human host
by the time it was identified as a novel virus."
Zeteo Biomedical to Collaborate with Iowa State University Nanovaccine Institute
to Study a COVID-19 Vaccine Under Fast Track CARES Act Funded Program
ISU's vaccine is "intended to address some of the limitations of the vaccines
currently in development by targeting room temperature storage
and single-dose nasal self-administration as key capabilities"
New research from Yale SOM's Heather Tookes and Matthew Spiegel, using what they
believe is the most comprehensive database of U.S. business interventions yet created,
finds that mask mandates, closing restaurants, and stay-at-home orders are all effective
at saving lives. Other commonly used measures, including closing low-risk businesses,
can actually worsen the spread of the pandemic.
"Mandatory mask policies seem to be as effective as policies that have higher costs."
(Simply recommending masks "doesn't do anything.")
https://medicalxpress.com/news/2020-11-restrictions-covid-deaths-worse.html
Louisiana State University applied computational models to investigate
infection rates in relation to social distancing measures in hard-hit U.S. states:
New York, New Jersey, Michigan, Massachusetts, Illinois, and Louisiana.
"Our current analysis suggests that
the face mask mandate is the most important policy for lowering the death count."
https://medicalxpress.com/news/2020-11-tracking-covid-trends-hard-hit-states.html
FDA EUA for Kantaro Biosciences' COVID-SeroKlir two-step ELISA diagnostic
yielding a false-negative rate of 1.2%, and a false-positive rate of 0.4%.
"COVID-SeroKlir is based on Mount Sinai technology
that was developed at the height of the COVID-19 pandemic in New York City.
It is a high performing test that quantifies antibody levels for individuals,
which medical professionals and policymakers alike can trust."
Their data shows robust antibody responses remaining relatively stable for 5 months.
The probability that a PCR test detected infection peaked at 77%
(54-88%) 4 days after infection, decreasing to 50% (38-65%) by 10 days after infection.
Testing every other day is estimated to detect 57% of symptomatic cases prior to onset
and 94% of asymptomatic cases within 7 days
https://www.medrxiv.org/content/10.1101/2020.11.24.20229948v1
Hospitals brace for another COVID-19 surge
The positivity rate in Newark, New Jersey's largest city, has hit 30% in some neighborhoods.
Last spring, nurses and doctors, eager to help in overflowing hospitals,
poured into New Jersey and New York from all parts of the country.
With SARS-CoV-2 now surging nationwide,
New Jersey hospitals must draw on their own resources of emotionally drained staff.
Buy a better mask NOW
"While there are still some shortages of medical masks,
health care workers have dedicated supply chains,"
former FDA commissioner Dr. Scott Gottlieb wrote in a Wall Street Journal Sunday op-ed.
"It's time to revise the guidance to consumers."
N95 and equivalent masks offer best protection against SARS-CoV-2.
Their equivalents include the KN95 from China and the FFP2 from Europe.
https://www.cnn.com/2020/11/24/health/us-coronavirus-tuesday/index.html
Based on genome-wide experiments, humans have 2,064 genes relevant to COVID-19,
but researchers study only 611 of them.
"... researchers tend to build upon existing knowledge and research tools.
They appear to select genes to study based on the ease of experimentation
rather than their ultimate relevance to a disease"
https://phys.org/news/2020-11-historical-bias-overlooks-genes-covid-.html
The latest research "shows":
* infections in children frequently go undetected (9% diagnosed at symptom onset)
* children are just as susceptible as adults to infection, but twice as likely asymptomatic
* children likely transmit the virus at a similar rate to adults in households
https://medicalxpress.com/news/2020-11-children-transmit-coronavirus-adults-school.html
Researchers from HEC Paris business school and Bocconi University in Milan calculate that
pandemic closures March - May saved 29,000 lives, costing economies about $6 million each.
https://phys.org/news/2020-11-bn-shutdowns.html
AstraZeneca AZD1222 positive high-level results from an interim analysis of clinical trials
No hospitalisations or severe COVID-19 cases reported in participants receiving AZD1222.
One dosing regimen (n=2,741) showed vaccine efficacy of 90%
when AZD1222 was given as a half dose, followed by a full dose at least one month apart.
Another regimen (n=8,895) showed 62% efficacy for two full doses at least one month apart.
Global trials are evaluating participants aged 18 years or over from diverse racial
and geographic groups who are healthy or have stable underlying medical conditions.
The vaccine uses a weakened version of a common cold virus
that is combined with genetic material for the SARS-CoV-2 spike protein.
The vaccine can be stored, transported and handled at normal refrigerated conditions
(2-8 degrees Celsius/ 36-46 degrees Fahrenheit) for at least six months.
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/azd1222hlr.html
In a rhesus macaque study, vaccine candidate AZD1222 reduced viral load,
which can reduce transmission potential; however,
it did not reduce nasal shedding or eliminate infectious virus in all animals,
which suggests that its potential for reducing transmission may not be great.
https://www.nature.com/articles/s41591-020-01172-x
AstraZeneca, which has pledged it won't make a profit on its vaccine during the pandemic,
has reached agreements with governments and international health organizations
that put AZD1222 cost at about $2.50 a dose. Pfizer's vaccine costs about $20 a dose,
while Moderna's is $15 to $25, based on agreements to supply the U.S. government.
https://apnews.com/article/astrazeneca-vaccine-third-cheaper-oxford-c99d26eb2946f6fde45a1edc002ff028
U.S. COVID-19 cases could nearly double before Biden takes office
"One of the key reasons for the increased accuracy of this model over other COVID-19
forecasts is that this model accounts for the fact that people live in interconnected
social networks rather than interacting mostly with random groups of strangers"
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding,
and infectiousness: a systematic review and meta-analysis
Although patients with SARS-CoV-2 infection might have prolonged RNA shedding
of up to 83 days in upper respiratory tract infection,
no live virus was isolated from culture beyond day 9 of symptoms
despite persistently high viral RNA loads. (10 pages)
https://www.thelancet.com/action/showPdf?pii=S2666-5247%2820%2930172-5
A new study confirms that testing half a population weekly with inexpensive,
rapid-turnaround COVID-19 tests would drive SARS-CoV-2 toward elimination within weeks
In one large city scenario, widespread twice-weekly testing with a rapid but less sensitive test
reduced the degree of infectiousness, R0 (R naught), by 80%.
But twice-weekly testing with a more sensitive PCR (polymerase chain reaction) test,
which takes up to 48 hours to return results, reduced infectiousness by only 58%.
In other scenarios, when the amount of testing was the same, the rapid test
always reduced infectiousness better than the slower, more sensitive PCR test,
because about two-thirds of infected people have no symptoms
and as they await their results, they continue to spread the virus.
https://scitechdaily.com/new-research-shows-frequent-rapid-testing-could-cripple-covid-19-within-weeks/
U.S., Germany and UK could start COVID-19 vaccinations as early as December
"Our plan is to be able to ship vaccines to the immunisation sites within 24 hours from the
approval, so I expect maybe on day two after approval on the 11th or the 12th of December,"
said head of the U.S. vaccine program, Moncef Slaoui.
OncoImmune's CD24Fc reduced the risk of respiratory failure or death
by more than 50% in hospitalized COVID-19 patients requiring oxygen.
Merck plans to acquire privately held OncoImmune for $425 million in cash.
"We realized that this small little company was in no position to make CD24Fc
to try and treat all of the people who could potentially benefit from this drug"
https://www.cnbc.com/2020/11/23/merck-acquires-oncoimmune-to-ramp-supply-of-promising-covid-19-drug.html
Virtual screening of anti-HIV1 compounds against SARS-CoV-2:
machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
2 of 1528 compounds screened are potential drugs against SARS-CoV-2
The first screened hit compound is
4-{[5-(2-Nitrophenyl)-2-furyl] methylene}-3-phenyl-5(4H)-isoxazolone (CID-230119).
The second is 4-Chloro-N-(1-methyl-1H-benzimidazole-5-yl) benzamide (CID-948801).
https://www.nature.com/articles/s41598-020-77524-x
3-D-printed nasal swab for COVID-19 testing
The final prototype, developed using FormLabs printers and surgical grade resin,
displayed statistically identical results to the flocked swab in the head-to-head trial.
FDA EUA was granted for Regeneron's COVID-19 experimental antibody cocktail treatment,
similar to an Eli Lilly treatment previously granted EUA which:
* also has limited availability,
* applies only to patients not seriously ill, and
* is administered by infusion only at a clinic or hospital.
In other words, only for the wealthy or otherwise entitled.
A simple direct RT-LAMP SARS-CoV-2 saliva diagnostic
Most RT-LAMP protocols require the purification of RNA,
a complex and low-throughput bottleneck that has often been subject to reagent supply shortages.
This protocol replaces RNA purification with a simple sample preparation step
using a widely available chelating agent and optimizes other parameters,
yielding sensitivity close to 90% and specificity close to 100%,
with 45 minutes from sample collection to result.
https://www.medrxiv.org/content/10.1101/2020.11.19.20234948v1
Incidence of SARS-CoV-2 infection among asymptomatic frontline health workers
in Los Angeles County, California April 8 - May 19 (16 pages)
Among 1787 enrolled, 10 tested positive for COVID-19, and 98 had antibodies.
https://www.medrxiv.org/content/10.1101/2020.11.18.20234211v1.full.pdf
A message from Southwest President, Tom Nealon
>> Don't just take it from me!
>> We've employed stringent cleaning and physical-distancing practices
>> such as using electrostatic and anti-microbial spray treatments in the cabin
Sanitation is nice, but nearly useless for mitigating COVID-19
>> We use HEPA (High-efficiency particulate air) onboard
>> that removes 99.97% of airborne particles*
In theory, that should be nothing new;
commercial passenger aircraft have been designed with HEPA filters for years.
Hopefully, more attention is now being paid to their maintenance.
>> - similar to the technology found in hospitals.
Not really; properly designed hospital ventilation controls flows
(e.g. by controlling pressure differentials between rooms and hallways)
>> exchange of cabin air every two to three minutes
That is a considerably higher exchange rate than in hospitals.
One problem is that folks sitting near aircraft HVAC returns
are exposed to fresh saliva aerosols before they are filtered.
A traveler should research the design of each aircraft
to reserve seats as far from HVAC returns as possible.
>> Because many people with COVID-19 may be asymptomatic,
For "many", substitute "most".
That is why travel CANNOT be safe unless/until ALL passengers are required
to STRICTLY quarantine for at least 10 days immediately prior to departure,
then wear an N95 mask and pass a COVID-19 diagnostic test before entering terminals,
spending absolutely minimal time inside terminals.
>> Southwest Airlines requires all travelers wear a face covering over their nose and mouth,
... but not necessarily very effective masks.
>> We are serving water and snacks on flights over 250 miles, when available
That is where it REALLY falls apart. Removing masks for water and snacks is doomed,
and spending enough time to need refreshments in aircraft increases transmission risk,
because airflow in aircraft cabins is NOT laminar; droplet densities will accumulate in eddys.
https://en.wikipedia.org/wiki/Eddy_(fluid_dynamics)
Bill Gates - COVID-19 Vaccines, Climate Change & A New Podcast | The Daily Social Distancing Show
I am far from a M$ fan, but Bill certainly could have found far worse retirement hobbies.
https://www.youtube.com/watch?v=dexryZiV-tg
On Friday, Pfizer and BioNTech submitted an EUA application to the FDA
for their COVID-19 vaccine candidate, and more than 195,500 new infections were reported.
The highest number of single-day cases during the country's summer surge
was a little more than 77,100 in July.
Colorado officials said a new modeling report estimates
about one out of every 49 residents in the state is infected with COVID-19.
In newly updated guidance, the CDC now says. At least 24 hospital leaders
warned the American Hospital Association they are experiencing staffing shortages
in states including Texas, Wisconsin, Illinois, Minnesota and North and South Dakota.
most COVID-19 infections are spread by people who have no symptoms.
https://www.cnn.com/2020/11/21/health/us-coronavirus-saturday/index.html
Maine's seven-day average for daily virus cases is now 188, up from just 32 one month ago.
COVID-19 hospitalizations surge to 90, a record level,
with hospitals in Bangor and Augusta bearing brunt.
"If we don't do something different, nothing is going to change.
We will stay on this trajectory of increasing cases,
which each passing day will make it harder and harder to put a lid on things."
https://www.pressherald.com/2020/11/20/daily-cases-over-200-again-in-maine-two-additional-deaths/
Schools are not spreading covid-19. This new data makes the case.
[ not confidence-inspiring that this article is labelled "Opinions"]
"The best available data suggests that infection rates in schools
simply mirror the prevalence of covid-19 in the surrounding community
- and that addressing community spread is where our efforts should be focused."
"...for high-school students and staff, the rates are similar to population case rates.
For elementary and middle school students, they are lower
- which we would expect, given the generally lower disease rate in younger children."
[ This also implies that younger children and their teachers are on average
safer in school than elsewhere. ]
Researchers model which approaches are most effective at reducing COVID-19 spread
Events were categorized as high or low transmission probability
The model suggests that physical distancing was effective
at reducing COVID-19 transmission in all settings
but the effectiveness of social bubbles
depends on whether chances of transmission are high or low.
Masks and other physical barriers may be less effective in high transmission settings
(parties, choirs, restaurant kitchens, crowded offices, nightclubs and bars)
because even if masks halve the transmission rates
that may not have much impact on the transmission probability
https://medicalxpress.com/news/2020-11-approaches-effective-covid-.html
Could frozen food transmit COVID-19? [ clickbait warning ]
Most international food safety authorities state that
there's no evidence of COVID-19 transmission through frozen foods.
Contaminated food or food packaging may give positive results under PCR test.
If the RNA in the virus is dead, the virus could not replicate further
https://theconversation.com/could-frozen-food-transmit-covid-19-148735
Testing half the population weekly with inexpensive, rapid-turnaround COVID-19 tests
would drive the virus toward elimination within weeks - even if
those tests are significantly less sensitive than gold-standard clinical tests,
according to a new study published today by University of Colorado Boulder
and Harvard University researchers,
provided that "personalized stay-at-home orders" were effective.
In one scenario, in which 4% of individuals in a city were already infected,
rapid testing 3 out of 4 people every 3 days reduced the number ultimately infected by 88%
and was "sufficient to drive the epidemic toward extinction within 6 weeks."
https://medicalxpress.com/news/2020-11-frequent-rapid-cripple-covid-weeks.html
A new study published in the journal of the American Society for Microbiology indicates that
mumps IgG titers, or levels of IgG antibody, are inversely correlated with
severity in recovered COVID-19 patients under age 42
previously vaccinated with measles-mumps-rubella (MMR II) vaccine.
"Based on our study, it would be prudent to vaccinate those over 40
regardless of whether or not they already have high serum MMR titers"
https://www.precisionvaccinations.com/can-mmr-vaccination-enhance-covid-19-immunity
~40% of patients hospitalized with COVID-19 are obese
the odds ratio for ICU admission were 3.16 for overweight
and 3.05 for obesity in the fully adjusted model, but overweightis not associated with death.
[ 6 pages; no graph provided ]
https://www.nature.com/articles/s41366-020-00721-1.pdf
Clinical evaluation of the Roche/SD Biosensor rapid antigen test
with symptomatic, non-hospitalized patients in a municipal health service drive-through testing site.
Around 98% of all viable specimen with high loads of viral RNA were detected successfully
indicating that the large majority of infectious people can be captured with this test..
two very potent SARS-CoV-2 antibodies, S2E12 and S2M11
S2E12 traps the spike in a conformation that cannot bind ACE2.
Both antibodies protected hamsters against SARS-CoV-2 challenge
and may be useful in antibody cocktails to combat the virus
and prevent the development of resistance.
https://science.sciencemag.org/content/370/6519/950
For COVID-19, most developers gambled on attacking its spike, the protein that allows
SARS-CoV-2 to dock onto and infect cells. This week's announcement by the biotech Moderna
that its COVID-19 vaccine powerfully protected people from the disease in an efficacy trial
was the strongest sign yet that spike is a winning hand. Anthony Fauci,
head of the U.S. National Institute of Allergy and Infectious Diseases (NIAID),
says he's "optimistic that all the vaccines are going to have very favorable results."
https://science.sciencemag.org/content/370/6519/894
Fresno bishop tells Catholics not to get COVID-19 vaccine
In his message, Brennan said the use of fetal cells at any stage of a vaccine's development
means Catholics cannot avail themselves of its scientific results.
Brennan did not explain why he singled out Pfizer's COVID-19 vaccine for criticism.
There is no indication that it was developed using either fetal cells or human embryonic stem cells.
The first 120,000 doses of CoronaVac,
a COVID-19 vaccine developed by China's Sinovac Biotech
that is being tested in Brazil,
arrived at Sao Paulo's international airport on Thursday morning.
SARS-CoV-2 virus images are misleading
"The virus doesn't look like that," because in reality all matter down at the nanometer
scale of atoms, molecules, and viruses "is continuously moving and vibrating.
They don't really look like those images in a chemistry book or a website."
Differences in vibrational characteristics correlate strongly with
the different rates of infectivity and lethality of different kinds of coronaviruses.
Nanox transparent stretchable PVC film
for use in packaging meat, fruit, cold cuts, and other foods, and to protect surfaces,
can inactivate 79.9% of SARS-CoV-2 in 3 minutes and 99.99% in up to 15 minutes.
The material contains silver and silica nanoparticles.
https://phys.org/news/2020-11-plastic-foods-surfaces-inactivates-coronavirus.html
A nasal spray that can provide effective protection against the COVID-19 virus
has been developed by researchers at the University of Birmingham,
using two polysaccharide polymers already widely approved
by regulatory bodies in the UK, Europe and the U.S.. [ repeat ]
"Products like these don't replace existing measures such as mask wearing and handwashing,
which will continue to be vital to preventing the spread of the virus.
What this spray will do, however,
is add a second layer of protection to prevent and slow virus transmission."
https://medicalxpress.com/news/2020-11-anti-covid-nasal-ready-humans.html
Three reasons why COVID-19 can cause silent hypoxia
Healthy lungs keep the blood oxygenated at a level between 95 and 100%; dipping below
92% is concerning, and a doctor might decide to intervene with supplemental oxygen.
1) some COVID-19 patients lose ability to restrict blood flow in damaged lung tissue
2) undetectably tiny blood clots form
3) mismatched air-to-blood flow in parts of the lung that appear normal on scans.
Modeling suggests that SARS-CoV-2 mutants with 1 or 2 mildly deleterious mutations
are expected to exist in high numbers due to neutral genetic variation,
and likewise resistance to single or double antibody combinations
will develop quickly under positive selection. (36 pages)
https://www.medrxiv.org/content/10.1101/2020.11.17.20233726v1.full.pdf+html
Biofunctionalized Two-dimensional MoS2 Receptors for
Rapid Response Modular Electronic SARS-CoV-2 and Influenza A Antigen Sensors
Selective responses in the presence of complementary antigens
with sensitivity to SARS-CoV-2 or influenza A on the order of pg/mL
and comparable to gold-standard diagnostics such as Polymerase Chain Reaction (PCR) analysis.
https://www.medrxiv.org/content/10.1101/2020.11.17.20233569v1
What if hardly anyone can get an FDA EUA COVID-19 treatment?
Hospitals lack infrastructure to administer bamlanivimab, Eli Lilly's monoclonal antibody,
Identifying which mildly ill patients, who have previously been told to stay home and isolate,
are at high risk of getting sick, then administering an hourlong medication drip,
and then monitoring another hour for side effects,
without impacting existing outpatient infusion centers serving e.g. immunocompromised chemotherapy patients.
More people are getting COVID-19 twice, suggesting immunity wanes quickly in some
To count as a case of reinfection, a patient must have had a positive polymerase chain reaction
(PCR) test twice with at least one symptom-free month in between.
The number of genetically proven reinfections is orders of magnitude lower
than that of suspected reinfections. Not all reinfections seen so far are milder. So far,
no proof exists of mutations that would make the virus more pathogenic or that might help the virus evade immunity.
A team of U.S. scientists shows SARS-CoV-2 can persist for months inside the gut.
Analysis of intestinal biopsies obtained from asymptomatic individuals 3 months after COVID-19 onset,
using immunofluorescence, electron tomography or polymerase chain reaction,
revealed persistence of SARS-CoV-2 in the small bowel of 7 out of 14 volunteers.
https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1
Herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 in vitro
Aqueous infusions prepared by boiling leaves of the Lamiaceae plants perilla and sage
elicit potent antiviral activity against SARS-CoV-2 in human cells.
Sustained antiviral activity was evident even when cells were treated
for only half an hour, and in therapeutic as well as prophylactic regimens.
Although the FDA generally recognizes sage as safe,
sage and perilla can cause allergic reactions. (26 pages)
COVID-19 transmission chain dynamics in Nordic countries
- Denmark, Finland, Iceland, Norway and Sweden - during first months of the pandemic:
Sweden experienced more numerous transmission chains, which tended to have more cases,
and were of longer duration, a set of features that increased with time.
Together with Denmark, Sweden was also a net exporter of SARS-CoV-2. (14 pages)
https://www.medrxiv.org/content/10.1101/2020.11.18.20233767v1.full.pdf+html
Estimating COVID-19 Virus Prevalence from Records of Testing Rate and Test Positivity
PCR testing for COVID-19 is not done at random but selectively on suspected cases.
This paper presents a method to estimate a 'genuine Virus Prevalence'
by quantifying and removing the bias related to selective testing.
Via pairing of 'genuine Virus Prevalence' with Excess-Deaths,
a 'genuine Infection Fatality Rate' (IFR) is also derived.
'Genuine Virus Prevalence' curves suggest that during the 1st epidemic wave,
curve flattening and waning happened at very modest levels of infection spread,
either naturally or facilitated by government measures.
[ This paper, based on earlier work with U.S. data, applies it to Western European data]
https://www.medrxiv.org/content/10.1101/2020.11.17.20233643v1.full.pdf+html (17 pages)
Among arbidol, azvudine, chloroquine, colchicine, favipiravir, hydroxychloroquine,
interferon B, ruxolitinib, lopinavir-ritonavir, methylprednisolone and remdesivir,
favipiravir (rank probability: 0.46) is most likely the best intervention against COVID-19,
followed by arbidol (rank probability: 0.18) and azvudine (rank probability: 0.15)
https://www.medrxiv.org/content/10.1101/2020.11.16.20232884v1.full.pdf+html (24 pages)
Regular universal random screening followed by isolation of infectious individuals
is not a viable strategy to reopen society after controlling a pandemic wave of SARS-CoV-2.
More targeted screening approaches are needed to better use rapid testing
such that it can effectively complement other control measures. (23 pages)
https://www.medrxiv.org/content/10.1101/2020.11.18.20233122v1.full.pdf+html
All else equal, an optimized vaccine allocation prioritizes states with a large number
of projected cases and subpopulations facing higher risks (e.g., older ones). Ultimately,
the optimized vaccine allocation can reduce the death toll of the pandemic by an
estimated 10-25%, or 10,000-20,000 deaths over a three-month period in the U.S. alone.
https://www.medrxiv.org/content/10.1101/2020.11.17.20233213v1.full.pdf+html (27 pages)
This paper introduces a concept called "age specific months of mortality" (MOMa),
a statistic that will allow people to understand their risk of death within their age group.
In a year without excess mortality, i.e. no pandemic, individual causes of death will add up
to a total of 12 MOMa. Excess mortality, e.g. a pandemic, adds MOMa beyond 12.
For people in their 20s, the MOMa is 5 for accidents, 1.9 for suicide, 1.6 for homicide,
and 1.2 for COVID-19.
For people in their 60s, the MOMa is 12 for COVID-19, 4 for cancer, 2.6 for coronary heart,
and treatment of COVID-19 with dexamethasone reduces MOMa from 12 to 7 months.
https://www.medrxiv.org/content/10.1101/2020.11.17.20233197v1.full.pdf+html (9 pages)
A new version of Siemens Healthineers's IgG antibody test,
launched over the summer,
quantifies antibodies capable of neutralizing the coronavirus. The test combines
recombinant fragments of the coronavirus spike protein's receptor binding domain
with an enzyme derived from horseradish roots.
Inhibiting TNF-a and IFN-y together protected against death in SARS-CoV-2 infection
Treatment with neutralizing antibodies against TNF-a and IFN-?
provided significant protection against SARS-CoV-2 induced mortality in mice.
While inhibiting cell death in the context of viral infection has a risk of increasing
the viral production from infected cells, a growing body of evidence suggests that
excessive cell death contributes more to disease pathology than does viral titer.
https://www.cell.com/cell/pdf/S0092-8674(20)31542-7.pdf (62 pages)
Seriously, it is past time to begin taking melatonin and famotidine
Thanksgiving will almost certainly provoke a COVID-19 infection spike,
reducing the chance of avoiding community transmission.
Both famotidine and melatonin are associated with reduced severity,
and 80 mg of famotidine 3x/day for 11 days is wanted as soon as illness is suspected.
Do the math and
you will want a lot of famotidine on hand.
"In patients hospitalized with COVID-19 and not initially intubated,
famotidine use was associated with a 2-fold reduction in clinical deterioration
leading to intubation or death"
FDA's first EUA for at-home COVID-19 molecular test to Lucira COVID-19 All-In-One Test Kit
"Antigen tests detect viral proteins and can provide results quickly. However,
they are not diagnostically definitive and are more likely to miss
an active coronavirus infection, or positive result, compared to molecular tests.
Molecular tests like Lucira's are 50 to 60 times more sensitive than antigen tests,
and considered the 'gold standard' for determining if someone is infected."
By early spring 2021, it is expected to be available nationally through health care providers.
Lucira anticipates its test will cost around $50.
https://drj.com/industry_news/fda-authorizes-first-prescription-at-home-molecular-test-for-covid-19/
Pfizer releases "final" results of its COVID-19 vaccine trial.
170 confirmed cases of COVID-19 were evaluated,
with 162 observed in the placebo group versus 8 in the vaccine group.
There were 10 severe cases of COVID-19 observed in the trial,
with 9 occurring in the placebo group and 1 in the BNT162b2 vaccinated group.
Efficacy was consistent across age, gender, race and ethnicity demographics;
observed efficacy in adults over 65 years of age was over 94%.
Fauci suggests he should have been 'much more vocal'
about COVID-19 testing early in pandemic
"Community spread doesn't stop spontaneously unless you do something about it,"
Fauci said in an interview with STAT's senior infectious diseases reporter, Helen Branswell.
"It is easier to stop when the level is relatively low. The only way that you can get at
community spread is that you need to test people who are without symptoms,
in order to show what the degree of penetrance of infection is."
https://www.statnews.com/2020/11/17/fauci-more-vocal-covid-19-testing/
Many buildings are poorly ventilated, adding to COVID-19 risks
The risk of catching COVID-19 indoors is 18.7 times higher than in the open air.
High carbon dioxide (CO2) levels indicate poor ventilation;
relative humidity readings of less than 40% are also concerning.
Demystifying the spreading of pandemics I:
The fractal kinetics SI model quantifies the dynamics of COVID-19
The poor predictive power of all models originates from the violation of
the fundamental hypothesis of the "well mixed" epidemiological system.
Results support that this "conceptual change" from classical to fractal kinetics principles
offers a novel, useful approach for the analysis of pandemics data. (16 pages)
https://www.medrxiv.org/content/10.1101/2020.11.15.20232132v1.full.pdf
Investigating duration and intensity of COVID-19 social-distancing strategies
Vaccines will reduce COVID-19 effective reproduction, but not to zero.
How to balance "moderate social-distancing" against capability limits of health-care systems? Delay effect of mitigation interventions
https://www.nature.com/articles/s41598-020-76392-9.pdf (11 pages)
Serological follow-up of SARS-CoV-2 asymptomatic subjects
About 80% of asymptomatic subjects did not present circulating immunoglobulins
against SARS-CoV-2 after 8 weeks from a positive nasal swab against the virus. Moreover,
in more than 40% of these subjects, no Ig against SARS-CoV-2 were detected at any time.
Finally, about two third of subjects with immunoglobulins at baseline
did not present IgG against SARS-CoV-2 after 8 weeks. The majority of subjects
who developed an asymptomatic infection do not present antibodies against the RBD-spike protein
after 8 weeks of follow-up.
https://www.nature.com/articles/s41598-020-77125-8
Fostamatinib for COVID-19 lung damage treatment
In July, a team at Imperial College London announced a phase 2 clinical trial
of fostamatinib in treating hospitalized COVID-19 patients with severe lung injury.
In October, the NIH and Inova Health System in the U.S. began a similar phase 2 trial.
This article describes research that identified fostamatinib.
https://medicalxpress.com/news/2020-11-lung-injury-covid-drug-trials.html
NIH is recruiting COVID-19 patients for fostamatinib treatment
https://nihrecord.nih.gov/2020/10/30/volunteers
Sweden bans public events with more than 8 people
The restriction is aimed at public events such as sporting events and concerts.
It doesn't extend to private gatherings and is enshrined in law as part of Sweden's
Public Order Act, which means there will be harsh penalties for violating them.
Lawbreakers could face fines or up to six months in prison.
Previously, events had been limited to 50 and then relaxed to 300 in some situations,
although different regions implement different restrictions
Moderna said its vaccine is expected to be stable at standard refrigerator temperatures
of 2 to 8 degrees Celsius (36 to 48F) for 30 days, up from a previous projection of seven days.
"You have the ability to maintain it at -20 degrees Celsius,
which is essentially a regular freezer temperature at home or medical freezer temperature
for up to six months of which up to 30 days can be at a regular refrigerator temperature,"
That contrasts with Pfizer Inc's vaccine candidate,
which must be shipped and stored at ultra cold temperatures or on dry ice
and can only last at standard refrigerator temperatures for up to five days.
more discussion (but does not answer title question)
How chemicals like PFAS can increase your risk of severe COVID-19
Endocrine-disrupting compounds (EDCs) are a broad group of chemicals
that can interfere with natural hormones in people's bodies in ways that harm human health.
They include perfluoroalkyl and polyfluoroalkyl substances, better known as PFAS,
flame retardants, plasticizers, pesticides, antimicrobial products and fragrances, among others.
Research has shown that people who are exposed to EDCs are more likely than others to develop metabolic disorders,
such as obesity, Type 2 diabetes and high cholesterol, and they tend to have poorer cardiovascular health.
EDCs can also interfere with normal immune system function, which plays a critical role in fighting off infection.
https://theconversation.com/how-chemicals-like-pfas-can-increase-your-risk-of-severe-covid-19-143167
Statement on Potential Intersection between PFAS Exposure and COVID-19
from the CDC is more tentative:
https://www.atsdr.cdc.gov/pfas/health-effects/index.html
Hepatitis C drugs boceprevir and narlaprevir can inhibit the SARS-CoV-2 main protease,
a crucial protein enzyme that enables the novel coronavirus to reproduce.
Room temperature X-ray measurements helped to build a three-dimensional map
that revealed how the atoms were arranged and where chemical bonds formed
between the SARS-CoV-2 main protease and drug inhibitor molecules.
"You can't design a drug without knowing how it works on a molecular level,
and the data we're providing is exactly what developers need to design
stronger, more tightly binding drugs for more effective treatments."
https://medicalxpress.com/news/2020-11-x-ray-explores-potential-hepatitis-drugs.html
Kids mount a COVID-19 immune response without detection of the SARS-CoV-2 virus.
Despite close contact with symptomatic infected parents,
the children repeatedly tested negative for COVID-19.
"The youngest child, who showed no symptoms at all, had the strongest antibody response"
https://medicalxpress.com/news/2020-11-kids-mount-covid-immune-response.html
Rapid antigen tests for the coronavirus are faster, cheaper and more user-friendly than standard diagnostic assays.
An assessment now shows that some, but not all, antigen tests can tell with high accuracy who is likely to be most infectious.
The five most sensitive antigen assays detected the presence of SARS-CoV-2 on 95% of tests
with high viral loads observed during the first week of symptoms
https://www.nature.com/articles/d41586-020-00502-w
Into the black
Readers will note that some localities are approaching 10% cumulative reported COVID-19 cases,
which almost certainly translates to 20% or more actual cases.
Constant readers might recall that my epidemial model
(which does NOT address immunity loss over time)
suggests that new infection rate may stop increasing so rapidly
when more than around 30% of populations are immune.
Since there are indications that immunity on average lasts perhaps only 6 months,
I contemplate adding another bar chart color code, namely black for infections after 6 months.
This will allow for bars beyond 100,000 hopefully never being gray, much less colored....
More than 11 million U.S. COVID-19 infections have been reported,
which could amount to perhaps 50 million actual infections.
[ 10 million was exceeded only a week ago. ]
[ Keep in mind that a 7-day average mostly represents an estimate for 3-4 days prior... ]
https://www.bbc.com/news/world-us-canada-54955093
Build a plan for COVID-19 home testing on reason, not speculation or politics
Some people will undoubtedly get false positive results and unnecessarily quarantine themselves.
Others will get false negative results and may unknowingly spread the virus to others.
Yet the benefits of testing far outweigh the risks.
[ co-written by the CEO of Global Diagnostic Systems,
a company developing a rapid home COVID-19 test ]
https://www.statnews.com/2020/11/16/build-covid-19-home-testing-plan-on-reason-not-speculation-or-politics/
Johnson & Johnson is confident that it has in Ad26.COV2.S (now also known as JNJ-78436735) a one-dose knockout vaccine against COVID-19,
but it's now starting a late-stage two-dose test of the same vaccine.
[ my guess: they want effectiveness competitive with already- announced mRNA results ]
In a separate development, J&J expanded partnership between its Janssen
and the U.S. Biomedical Advanced Research and Development Authority (BARDA)
for the ongoing development of Janssen's COVID-19 vaccine candidate,
in which Janssen will commit around $604m
while BARDA will offer $454m to support the Phase III ENSEMBLE trial.
https://www.pharmaceutical-technology.com/news/janssen-ensemble-2-trial/
"Our findings support the use of BMI and LDL cholesterol as important metrics
alongside other known characteristics (such as age and ethnicity)
in the risk assessment of vulnerability to COVID-19 infection."
https://medicalxpress.com/news/2020-11-obese-people-covid-.html
IgG detection alone is insufficient for the diagnosis of active or cured COVID-19.
Abbott's SARS-CoV-2 IgG assay and the PanbioTM COVID-19 IgG/IgM rapid test device
both showed 98% agreement for IgG detection. IgM detection has a limited diagnostic value.
https://www.nature.com/articles/s41598-020-76914-5
Ranking effectiveness of worldwide non-pharmaceutical COVID-19 interventions
A consensus set of non-pharmaceutical interventions (NPIs) leading to significant Rt reduction
A clear picture emerges where the themes of social distancing and travel restrictions
are top ranked in all methods, whereas environmental measures
(for example, cleaning and disinfection of shared surfaces) are ranked least effective.
https://www.nature.com/articles/s41562-020-01009-0.pdf (18 pages)
school reopenings done wrong in both red and blue states
"there is little data to support the idea that schools are a major site of transmission
or a driver of community spread"
If closing schools is the only intervention a jurisdiction takes to control its COVID-19 epidemic,
incidence will continue to rise and schools will remain shuttered indefinitely.
Quickly closing schools while leaving higher-risk establishments open does not make sense
Districts that have seen more COVID-19 in their schools have 2 things in common:
1) They opened when case rates in the community were very high,
clearly higher than public health guidance recommends for safe reopening.
For example, when Utah opened schools,
the 14-day moving average of COVID-19 case rate in the community was 187 per 100,000 people,
far above CDC's threshold for "lower risk" reopening, which is 50 per 100,000 people.
2) They did not have statewide mask mandates, or masks were not routinely in use.
Sex differences in the decline of neutralizing antibodies to SARS-CoV-2 (13 pages)
In a longitudinal study of sera from 308 RT-qPCR+ individuals with mild disease,
collected at two time-points, up to 6 months post-onset of symptoms (POS):
* at month one: males, individuals > 50 years of age or with a body mass index (BMI) > 25
exhibited higher levels of antibodies. Antibody levels decreased over time.
* for months 3-6: anti-S antibodies persisted in 99% of individuals,
while anti-N IgG were measurable in only 59% of individuals.
Anti-Spike and NAbs decline was faster in males than in females, independently of age and BMI.
https://www.medrxiv.org/content/10.1101/2020.11.12.20230466v1.full.pdf
A cohort of previously RT-PCR+ve (detected by nasopharyngeal swab during the acute phase),
male convalescent patients, all with mild symptoms,
were enrolled on serial blood sample collection
for evaluation of longitudinal nAb titers and antibodies (IgM, IgG and IgA).
25% of donors kept nAb titers =160, for a median of 100 days after disease onset:
there was a high probability of sustaining nAB titers =160
in volunteers whose initial nAb titer was =1280,
weight = 90kg or BMI classified as overweight or obese.
There was no correlation between ABO group, ABO antibody titers
and persistent high nAb titers.
https://www.medrxiv.org/content/10.1101/2020.11.12.20230391v1
COVID-19 COGNITIVE DEFICITS AFTER RESPIRATORY ASSISTANCE
IN THE SUBACUTE PHASE: A COVID-REHABILITATION UNIT EXPERIENCE
Patients with severe functional impairments
had important cognitive and emotional deficits
which might have been influenced by the choice of ventilatory therapy,
but mostly appeared to be related to aging,
independently of Functional Independence Measure (FIM) scores.
https://www.medrxiv.org/content/10.1101/2020.11.12.20229823v1
COVID-19 virulence may be more severe in Europe and North America
due to coinfection with different SARS-CoV-2 strains
leading to genomic recombination which might be challenging
for current treatment regimens and vaccine development.
This study provides a possible explanation for the more severe second wave of COVID-19
that many countries are currently experiencing presented as higher rates of infection and death.
(33 pages)
https://www.medrxiv.org/content/10.1101/2020.11.11.20229765v1.full.pdf
Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies.
Antibody functions were analyzed in 52 asymptomatic infected individuals,
119 mild and 21 hospitalized COVID-19 patients.
Antibody levels and activities are slightly lower in asymptomatic individuals.
The different functions of the antibodies are correlated, independently of disease severity.
https://www.medrxiv.org/content/10.1101/2020.11.12.20230508v1
Remdesivir parent nucleotide analog, GS441524,
which targets the coronavirus RNA-dependent RNA polymerase enzyme,
and a feline coronavirus prodrug, GC376, which targets its main protease,
were tested on SARS-CoV-2 infected mice.
Low-dose combined application of GS441524 with GC376
could effectively protect mice against SARS-CoV-2 infection
via combined intranasal and intramuscular treatment.
https://www.biorxiv.org/content/10.1101/2020.11.12.380931v1
In a BBC interview, Prof Ugur Sahin, BioNTech co-founder, said
"I'm very confident that transmission between people
will be reduced by such a highly effective vaccine
- maybe not 90% but maybe 50% - but we should not forget that even that
could result in a dramatic reduction of the pandemic spread."
"Summer will help us because the infection rate will go down in the summer
and what is absolutely essential is that
we get a high vaccination rate until or before autumn/winter next year."
https://www.bbc.com/news/health-54949799
Nearly 17% of recovered COVID-19 patients could still carry the virus
There was no significant difference between patients with positive and negative test results
in terms of age or sex. The only two symptoms that were higher and significantly prevalent
in patients with a positive test were sore throat (18 vs. 4%) and signs of rhinitis (27 vs. 2%).
One of President-elect Joe Biden's coronavirus advisors,
University of Minnesota epidemiologist Michael Osterholm, told The Washington Post that
only a national lockdown can bring the pandemic under control at this point.
But Osterholm said he has no hope the country has the will to enact such a policy.
"I'm smart enough to know when something is not going to happen," he said. "All I can do is
hold it out there. It is going to be, mark my words, the only thing that will stop this runaway train."
Lock Yourself Down, Now
Almost every day, America is breaking new records in confirmed COVID-19 cases;
they are up 40% from just one week ago. Cases are not confined to a region or a state;
the whole nation is in the midst of a terrible surge.
All of this means we desperately need to flatten the curve, again,
before hospitals nationwide are overrun. Trevor Bedford, a
scientist at the Fred Hutchinson Cancer Research Center, in Seattle,
calculates that more than 2,000 deaths a day may already be baked in for early December,
meaning that even if all new infections stopped today,
that many people will still die per day in just a few weeks among those already infected.
https://www.theatlantic.com/health/archive/2020/11/lock-yourself-down-now/617106/
In about 25 days, if all goes according to schedule, the FDA's vaccine advisory committee
will recommend expanding the public use of the first vaccine against the coronavirus.
If the FDA authorizes expanded use of the vaccine in December,
it would occur 11 months after SARS-CoV-2 was first identified
- three years faster than any other vaccine has ever been developed.
According to a recent analysis, 3 out of every 4 Americans
would need to receive a vaccine that prevents at least 80% of infections
for that vaccine to extinguish this pandemic on its own.
In the past decade, the U.S. has never managed to vaccinate
more than half of adults for seasonal influenza in any single year;
in most years, coverage hovers around 40%.
https://www.theatlantic.com/ideas/archive/2020/11/science-working-society-needs-step-up/617107/
As coronavirus cases surge across PA and hospitalizations rise,
2,200 nurses across 3 hospitals in the Philadelphia region voted to authorize a strike if,
among other issues, they couldn't get their employers to commit to minimum staffing levels.
"Some of us were taking three patients at a time when we should never have more than two,
and sometimes these patients, they're so sick, they're meant to have one nurse."
Compromised humoral functional evolution tracks with SARS-CoV-2 mortality
Surviving COVID-19 requires development of IgG antibodies with strong Fc-receptor binding.
This research again confirms that recovery requires
immune systems recognizing and targeting the S2-domain of SARS-CoV-2 spike proteins.
https://www.cell.com/cell/pdf/S0092-8674(20)31459-8.pdf
In a study of 168 blood samples, the majority of the COVID-19 patients
with acute respiratory failure not only did not have a cytokine storm, an immune overreaction,
they had less inflammation than influenza patients who were equally ill.
"In the population we studied, 24% died but only 4% had a cytokine storm"
A meta-analysis published in September placed the percentage who benefit from
steroid drugs such as dexamethasone that suppress inflammation between 2% and 9%.
The cause of most cases of respiratory failure in COVID-19 patients remains unknown.
https://medicalxpress.com/news/2020-11-respiratory-failure-covid-driven-cytokine.html
[ but see yesterday's article about autoantibodies against interferons ]
https://www.fiercebiotech.com/medtech/breakthrough-finding-reveals-why-certain-covid-patients-die
{ I do not preferentially seek out bad news, but did sort better news later }
Promising potential COVID-19 treatment found, funded by Emergent BioSolutions
"We determined that disrupting the SKI complex keeps the virus from copying itself,
which essentially destroys it. We also identified compounds that targeted the SKI complex,
not only inhibiting coronaviruses but also influenza viruses and filoviruses,
such as the one that causes Ebola."
"Compounds predicted to bind were purchased and screened for antiviral activity."
Their most effective drug is called UMB 18-2. (12 pages)
https://www.pnas.org/content/early/2020/11/11/2012939117
The rheumatoid arthritis drug baricitinib can block viral entry and reduce mortality 71%
in patients with moderate to severe COVID-19, according to translational research
by an international team coordinated by researchers from Karolinska Institutet in Sweden.
Patients had a median age of 81 years.
https://advances.sciencemag.org/content/early/2020/11/13/sciadv.abe4724
10% of COVID-19 patients who developed life-threatening pneumonia had autoantibodies
Only 4 of 1227 other patients had autoantibodies. An additional 3.5% of critically ill patients
had mutations in genes that control the interferons involved in fighting viruses.
94% of patients in the study with the autoantibodies were men;
12.5% of men with life-threatening COVID-19 pneumonia had autoantibodies against interferon,
compared with 2.6% of women,
despite autoimmune diseases presenting with a 2:1 greater prevalence amongst women.
[ no indication whether above statistics account for other risk factors ]
Critical care workers have lower seroprevalence of SARS-CoV-2 IgG
compared with non-patient facing staff in first wave of COVID19.
(9% patient facing critical care, 15% patient facing non-critical care, 22% nonpatient facing)
https://www.medrxiv.org/content/10.1101/2020.11.12.20145318v1
Freezers needed to properly store Pfizer's vaccine are
"almost like unicorns in health care - they're far and hard to find,"
said Soumi Saha, PharmD, JD, the senior director of Premier, Inc
"We have a series of packaging
- we call them pizza boxes because they have roughly that shape full of vaccine
and they're packed around with dry ice in these very insulated containers,"
said Pfizer's chief scientific officer of viral vaccines, Dr. Phil Dormitzer.
https://abcnews.go.com/Health/reality-pfizers-covid-19-vaccine-distribution-plan/story?id=74183968
Model Calculations of Aerosol Transmission and Infection Risk of COVID-19 in Indoor Environments
Aerosols from highly infective subjects can effectively transmit COVID-19 in indoor environments.
This "highly infective" category represents approximately 20% of the patients who tested positive for SARS-CoV-2.
We find that "super infective" subjects, representing the top 5-10% of subjects with a positive test,
plus an unknown fraction of less - but still highly infective, high aerosol-emitting subjects
may cause COVID-19 clusters (>10 infections). In general, active room ventilation
and the ubiquitous wearing of face masks (i.e., by all subjects) may reduce the individual infection risk
by a factor of five to ten, similar to high-volume, high-efficiency particulate air (HEPA) filtering.
A particularly effective mitigation measure is the use of high-quality masks,
which can drastically reduce the indoor infection risk through aerosols.
https://www.mdpi.com/1660-4601/17/21/8114/pdf (18 pages)
Association of social distancing and masking with risk of COVID-19
Individuals living in communities with the greatest social distancing
had a 31% lower risk of predicted COVID-19
compared with those living in communities with poor social distancing.
Self-reported masking was associated with a 63% reduced risk of predicted COVID-19
even among individuals living in a community with poor social distancing.
https://www.medrxiv.org/content/10.1101/2020.11.11.20229500v1
Thursday, federal health officials reached an agreement with pharmacies across the U.S.,
including retail chains like Rite Aid and Walgreens, supermarket drug stores like Albertsons and Publix,
and big box stores like Costco and Walmart, to distribute free coronavirus vaccines
after they are approved and become available to the public. The agreement follows
a collaboration with CVS and Walgreens to deliver vaccines to nursing homes and administer shots.
https://medicalxpress.com/news/2020-11-feds-covid-vaccine-agreement-drug.html
According to COVID-19 modelers:
* Only one U.S. wave, not 3; unlike 1918 flu, there has been no significant COVID-19 trough
* death rate doubling , roughly, in the next 3 weeks is inevitable
* new cases depend largely on general population [mis]behavior, which may change,
but current trends will cause total U.S. COVID-19 deaths to more than double.
(Poor data collection for faster and cheaper tests make official daily cases less representative).
The way we [ab]use data is a life or death matter
Florence Nightingale was also a statistician
Dark data (not collected)
Data positivism (fit to traditional visualizations)
Data washing (expectations and click bait)
Bristol scientists demonstrated a new virtual reality [VR] technique
which should help in developing drugs against SARS-CoV-2
and enable researchers to share models and collaborate in new ways.
"We've shown that interactive virtual reality can model
how viral proteins and inhibitors bind to the enzyme." (25 page pdf)
https://pubs.acs.org/doi/10.1021/acs.jcim.0c01030
After reimposing tough curbs this month to help slow the outbreak,
Germany is seeing tentative signs that its surge in coronavirus infections may be easing,
officials said Thursday, giving credit to anti-transmission measures
that they warned would have to be maintained through winter and beyond.
With an eye on rising infections in schools, several German states have mooted
the idea of lengthening the Christmas vacation
to keep the population home and break the chain of transmission.
Merkel has warned that only when 60 to 70% of the population has achieved immunity
can COVID-19 be deemed to have been "more or less overcome".
https://pubs.acs.org/doi/10.1021/acs.jcim.0c01030
The accuracy of a rapid finger-prick antibody test for SARS-CoV-2
may be considerably lower than previously suggested.
The AbC-19TM Rapid Test, previously suggested to yield no false positive results,
has now been shown to report around 20% false positives among those previously infected.
https://medicalxpress.com/news/2020-11-accuracy-rapid-covid-previously.html
MIT chemists have determined the molecular structure of SARS-CoV-2 envelope protein E,
which forms a cation-selective channel and plays a key role in the virus's ability
to replicate itself and stimulate the host cell's inflammation response.
Cloning and purifying the E protein took two and half month,
then they measured NMR spectra for two months, nonstop,
on the highest-field NMR instrument at MIT, a 900-megahertz spectrometer,
as well as on 800- and 600-megahertz spectrometers. Two drug treatments
(amantadine, used for influenza, and hexamethylene amiloride, used for high blood pressure)
have been found to block the E channel entrance.
However, these drugs bind only weakly to the E protein.
https://phys.org/news/2020-11-chemists-key-coronavirus-protein.html
Sick health workers
To ease some of the burden on hospitals facing staffing shortages
as doctors and nurses become infected
or self-quarantine due to contact with an infected person,
North Dakota is allowing health-care workers with asymptomatic COVID-19
to continue working in coronavirus wards
Ohio hospital executives said they will need to at least delay some care
if staffing shortages continue and possibly turn people away.
Ohio's seven-day average number of infections was 4,723 on Monday,
up from 3,097 a week earlier.
Local officials in Maryland are calling on Gov. Larry Hogan (R)
to pull the state back from the third phase of its recovery plan
and reimpose certain restrictions on social and commercial activity
Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae,
and a psychiatric diagnosis might be an independent risk factor for COVID-19.
Among 62,354 patients diagnosed with COVID-19 between Jan 20, and Aug 1, 2020,
the incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis
was 18.1%, including 5.8% that were a first diagnosis.
https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30462-4/fulltext
Restaurant, gym and hotel reopenings carry the highest danger of spreading COVID-19,
according to a study that used mobile phone data from 98 million people
to model the risks of infection at different locations.
https://www.nature.com/articles/s41586-020-2923-3
Coronavirus spread hits record levels in Maryland, Virginia amid national spike
Maryland saw a record-high number of infections on Monday for the third consecutive day,
leaping past Virginia to record the highest rate of spread in the greater Washington region.
Monday's U.S. seven-day average of new infections per 100,000 residents was 33.
That number was 14 in D.C., 17 in Virginia and 20 in Maryland.
Hugh Grant Describes What It Was Like Getting Coronavirus
"This feeling as though some enormous man was sitting on my chest,
sort of Harvey Weinstein" [ Colbert alert ]
Can a nose-full of chicken antibodies ward off coronavirus infections?
To make the chicken antibodies, inject the spike protein into the chests of chickens.
The birds mount a vigorous immune response to it,
which includes laying eggs that contain antibodies against the coronavirus protein.
Harvest the chicken antibodies, called immunoglobulin Y, from egg yolks
and formulate the nasal drops. "The concept, in principle, sort of makes sense"
Researchers are assessing anti-IgY responses in rats. A "challenge" study in hamsters,
in which scientists would give them nasal drops and then try to infect the rodents
and cause disease, has been stalled because those animals remain in short supply.
Instead, a clinical safety trial is being conducted on Australians.
If that trial establishes safety, reveals no obvious side effects,
and doesn't find a significant response against the chicken antibody,
SPARK hopes to launch an efficacy trial in the U.S..
"The number of COVID-19 patients in Australia is zilch, so we have to come back here,"
with discussions for such a study under way with the U.S. FDA.
More about Pfizer's "90%" mRNA vaccine
If the vaccine is formally deemed safe and effective or given an EUA by FDA and regulators in other countries,
an ethical dilemma comes to the fore: whether to offer it to the participants in the study who received the placebo,
which could compromise the trial's ability to collect more data on the durability of its immune response and safety.
Other COVID-19 vaccine trials might also be compromised: Participants might drop out if they can access a 90% effective vaccine.
"By combining single-particle nanopore sensing with artificial intelligence,
we were able to achieve highly accurate identification of multiple viral species"
https://phys.org/news/2020-11-viruses-machine.html
ORF3d is a newly identified overlapping gene in SARS-CoV-2
that has the potential to encode a protein that is longer than expected.
It elicits a strong antibody response in COVID-19 patients,
demonstrating that its protein is manufactured during human infection.
https://phys.org/news/2020-11-hidden-gene-covid-virus.html
Key elements of the bradykinin, angiotensin and coagulation systems
are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics,
which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry
result in the development of the three most severe clinical components of COVID-19.
[ 19 pages, nicely illustrated ]
https://www.nature.com/articles/s41598-020-76488-2
Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards
Detection of SARS-CoV-2 in central ventilation systems, distant from patient areas,
indicate that virus can be transported long distances
and that droplet transmission alone cannot reasonably explain this,
especially considering the relatively low air change rates in investigated wards.
https://www.nature.com/articles/s41598-020-76442-2
Novavax NVX-CoV2373 COVID-19 Vaccine Granted Fast Track Designation by U.S. FDA
Novavax expects to begin its U.S. Phase 3 clinical trial by the end of November.
Its ongoing Phase 3 clinical trial in the UK is expected to be fully enrolled by the end of November.
Interim data in the UK trial are expected as soon as early first quarter 2021.
[ As a reminder, the Pfizer BNT162b2 ("90%") vaccine requires storage as low as -176F.
Dry ice is its likely shipping coolant.
Novavax' NVX-CoV2373, a protein subunit vaccine, can survive at room temperature,
with storage in regular refrigerators ]
FDA Fast Track designation
Pfizer did not actually delay reporting good news
Vaccine trials are overseen by independent "data and safety monitoring boards" (DSMBs)
that include scientists and statisticians with no ties to vaccine makers.
Before a study completes, only its DSMB can unlock the code of who got vaccine, who got placebo,
and to recommend if the shots are working well enough to stop testing early.
DSMBs interim analyses occur at times predetermined by manufacturers and the FDA.
The first interim analysis for Pfizer came Sunday.
https://apnews.com/article/covid-vaccine-timeline-testing-explainer-eabe7c36989357bf224edc94214b23ff
Pfizer's COVID-19 Vaccine: 11 Things You Need to Know
Pfizer did not accept federal funding to help develop or manufacture BNT162b2,
unlike Moderna and AstraZeneca. Pfizer's $1.95B Operation Warp Speed deal
is an advance-purchase agreement; no payment until delivery of 100 million doses.
https://www.nytimes.com/2020/11/09/health/pfizer-covid-19-vaccine.html
Biologist uses rabies-like virus to illuminate how SARS-CoV-2 blocks immune response
VSV is a rabies-like virus that predominantly infects cattle, horses and pigs
with similar characteristics to the SARS-CoV-2 protein, in that it acts to tamp down
interferons that would otherwise kick off an immune response in infected patients.
https://medicalxpress.com/news/2020-11-biologist-rabies-like-virus-illuminate-sars-cov-.html
atrial fibrillation (a-fib) may increase COVID-19 outcome risk
20% of patients hospitalized with COVID-19 suffered an a-fib episode.
Many had a history of the condition, but not all.
More than half had a heart attack, compared to 30% who did not have in-hospital a-fib.
https://medicalxpress.com/news/2020-11-a-fib-heighten-covid.html
"Because so many workers are in essential jobs and unable to work at home,
and because so many adults have increased risk of severe COVID-19, we found that
between 57 million and 74 million adults with increased risk of severe COVID-19
were either essential workers unable to work at home
or they lived in households with such workers"
https://medicalxpress.com/news/2020-11-million-essential-workers-high-covid.html
Recent research supports melatonin as possible COVID-19 treatment
Melatonin usage was associated with a nearly 30% reduced likelihood of testing positive
for SARS-CoV-2 after adjusting for age, race, smoking history and various disease comorbidities.
Notably, the reduced likelihood of testing positive for the virus
increased from 30 to 52% for African Americans when adjusted for the same variables.
https://medicalxpress.com/news/2020-11-melatonin-covid-treatment.html
California seeing biggest jump in COVID-19 cases in months
LA county was seeing 750 cases per day in September. Last week,
four days saw case counts above 2,000
The number of people who test positive climbed from 2.5% to 3.7% in about 3 weeks,
hospitalizations are 29% over 14 days and "that trendline continues up"
https://medicalxpress.com/news/2020-11-california-biggest-virus-cases-months.html
microfluidic RT-PCR assay could markedly reduce the false-negative rate
of SARS-CoV-2 clinical diagnostic tests
[ no mention of impact on false-positive rate ]
https://www.mdpi.com/2227-9717/8/11/1425/htm
Pfizer and BioNTech claim COVID-19 vaccine candidate effectiveness > 90%
based on an evaluable case count of 94, at 7 days after the second dose.
They estimate that the amount of safety data specified by the FDA in its guidance for
potential Emergency Use Authorization will be available by the third week of November..
Pfizer and BioNTech's BNT162b2 vaccine requires storage as low as -80C.
That may be a logistical nightmare for distributing the vaccine,
as thousands of costly, new ultra-cold freezers would be needed.
Pfizer is also developing a custom box that can keep the vaccine cold in transit.
The question is whether this can be scaled up to vaccinate hundreds of millions of people
across the U.S., and possibly billions around the world.
https://www.vox.com/21556359/pfizer-vaccine-covid-19-biontech-trial-results-coronavirus
Federal data from 20 states finds that new weekly cases among residents
rose nearly four-fold from the end of May to late October, from 1,083 to 4,274.
Alaska, Arkansas, Iowa, Idaho, Indiana, Kansas, Kentucky, Minnesota, Missouri,
Montana, Nebraska, New Mexico, North Dakota, Ohio,
Oklahoma, South Dakota, Utah, Wisconsin, West Virginia, and Wyoming.
"Trying to protect nursing home residents without controlling community spread
is a losing battle"
https://apnews.com/article/596ef4bfe18313ae72368e2c86e85f27
COVID-19 infections are increasing in 43 states; more than 230,000 cases this weekend
"We're about to see all of these little epidemics across the country, crossed and mixed"
[ noTHANKSforGIVING friends and relatives COVID-19 along with a big meal ]
https://www.cnn.com/2020/11/09/health/us-coronavirus-monday/index.html
Proinflammatory IgG Fc structures in patients with severe COVID-19
severe COVID-19 produced a unique serologic signature,
including an increased likelihood of IgG1 with Fc glycans lacking fucose sugar.
https://www.nature.com/articles/s41590-020-00828-7
Real-time, interactive website for U.S.-county-level COVID-19 event risk assessment
[ poor color coding; for 10 attendees: 7% in Beaufort Co SC; 8% in Fairfax Co, VA;
26% in Fayette Co, KY; 10% in Cayuga Co, NY; 30% in Franklin Co, MO; 6% in Travis, TX ]
https://covid19risk.biosci.gatech.edu/
Given an event size and county, this map estimates risk (0-100%)
that at least 1 COVID-19 positive individual will be present,
using a binomial probability model.
https://www.nature.com/articles/s41562-020-01000-9
[Hesperidin was first isolated in 1828 from the white inner layer of citrus peels.]
Hesperidin is a classical herbal medicine used worldwide for a long time
with an excellent safety profile.
Hesperidin may help blood vessels function better and reduce inflammation.
Clinical trial of Hesperidin and Diosmin for Treatment of COVID-19
https://clinicaltrials.gov/ct2/show/NCT04452799
The mutated SARS-CoV-2 which appears to have spread from minks to humans in Denmark
was detected previously at a Netherlands mink farm, but it did not infect humans there.
https://www.bbc.com/news/science-environment-54867653
U.K. study: Severe COVID-19 cases may age brains by 10 years
Cognitive abilities of more than 84,000 suspected or confirmed patients were tested
after controlling for other factors such as age, gender and pre-existing medical conditions.
"Although these deficits were on average of small scale for those who remained at home,
they were more substantial for people who had received
positive confirmation of COVID-19 infection"
https://www.sfgate.com/news/editorspicks/article/U-K-study-Severe-COVID-19-cases-may-age-brains-15686431.php
SC COVID-19 new cases rose by nearly 12%
8,130 cases were reported this week; the previous week had 7,271
Saturday's 1639 cases is the highest single day count since July 30.
13.1% of tests returned positives.
An Explanation for Some COVID-19 Deaths May Not Be Holding Up
Patients who died from COVID-19 had been discovered to generally have little or no virus.
Their immune methods removed it, but in doing so, presumably went rogue,
spewing out cytokines and different drivers of inflammation that fatally broke tissues and organs in a storm.
The storm concept has thus far centered on one cytokine, interleukin-6, or il-6,
but a generally used il-6 inhibitor, tocilizumab, is typically not useful,
and il-6 levels in critically ill COVID-19 patients range from regular to barely increased.
https://lightlynews.com/2020/11/08/health/an-explanation-for-some-covid-19-deaths-may-not-be-holding-up/
SARS-CoV-2 antibodies differ between children and adults
[ is multisystem inflammatory syndrome children's equivalent to adults' immune 'storm'? ]
Children produced fewer antibodies against the virus's spike protein.
Children's antibodies had the least neutralizing activity,
while adults' neutralizing activity increases with disease severity.
https://medicalxpress.com/news/2020-11-children-antibodies-response-sars-cov-.html
How SARS-CoV-2 spike mutations attenuate monoclonal and serum antibody neutralization
VSV-eGFP-SARS-CoV-2-S chimeric virus was used with 19 neutralizing monoclonal antibodies (mAbs)
against the receptor binding domain (RBD) to generate 48 escape mutants.
These variants were mapped onto the RBD structure and evaluated for cross-resistance by convalescent human plasma.
Single amino acid substitutions were identified that could attenuate neutralizing immune responses in some humans.
https://www.biorxiv.org/content/10.1101/2020.11.06.372037v1
Looks like rescaling will soon be required to avoid legend collision
Philadelphia reported 742 new cases of the coronavirus in the city on Friday, marking the highest number of daily cases the city has seen since the pandemic began.
14% of the tests reported Friday came back positive;
daily case counts have increased by fourfold since late September,
and cases are rising across every age group.
"This is possibly the worst period of the entire epidemic."
Only about 75% of Philadelphians are wearing masks while leaving retail stores.
https://phillycom.cmail20.com/t/d-l-cdrkrdt-tlhhjttjir-c
[ somehow, all the following got wiped out, first time round: ]
UK bans Denmark visitors over mink COVID-19 fears
Concern that SARS-CoV-2 mutations transmitted back to humans
may defeat vaccines being developed.
https://www.bbc.com/news/uk-5485104
'It's a slaughter,' doctors say of new coronavirus wave
The share of coronavirus diagnostic tests coming back positive has risen to 8.2% this week;
last week's share of positive tests was 7.2%.
https://news.yahoo.com/coronavirus-wave-152513366.htm
strategy to create COVID-19 drugs to inhibit both entry and replication
Some existing compounds can inhibit both the main protease (Mpro),
a key viral protein required for SARS-CoV-2 replication inside human cells,
and the lysosomal protease cathepsin L,
a human protein important for viral entry into host cells.
https://medicalxpress.com/news/2020-11-reveals-strategy-covid-drugs-inhibit.htm
Mucus production stimulated by IFN-AhR signaling triggers COVID-19 hypoxia
Surfaces of cells lining the respiratory tract are coated with mucus,
which is vital to ensure trapping of inhaled particles and pathogens.
Physiologically, mucus is ordinarily expelled out by the movement of cilia,
which also prevents bronchiolar mucus from dropping into the lumens of alveoli
where pneumocytes do not express cilium. However,
mucus adherence and accumulation in the alveoli may increase the thickness of blood-gas barrier,
thus hindering the exchange of O2 and CO2.
https://www.nature.com/articles/s41422-020-00435-
Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination
Exosomes are small bubbles released from cells that may contain proteins,
lipids, nucleic acids and genetic material. Combinatorial vaccine candidate
LSNME/SW1 contains purified exosomes loaded with mRNAs designed to express
an artificial fusion protein, LSNME, that contains
portions of the viral spike, nucleocapsid, membrane, and envelope proteins, and
Acrylamide Fragment Inhibitors that Induce Unprecedented Conformational Distortions
in Enterovirus 71 3C and SARS-CoV-2 Main Protease
[ Acrylamide is highly toxic and likely carcinogenic]
Warping SARS-CoV-2 spikes may impact their contagion, but enough to die for..?
https://www.biorxiv.org/content/10.1101/2020.11.06.370916v1.full.pd
Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2
Camelid immunization and proteomics to identify a large repertoire
of highly potent neutralizing nanobodies (Nbs) to the SARS-CoV-2 spike (S)
protein receptor-binding domain (RBD).immunization and proteomics identify
a large repertoire of highly potent neutralizing nanobodies (Nbs)
to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD).
These thermostable Nbs can be rapidly produced in bulk from microbes
and resist lyophilization, and aerosolization.
https://science.sciencemag.org/content/early/2020/11/04/science.abe4747
a computational protein design strategy enables rapid and accurate design of
hyperstable protein "decoys" that replicate the protein receptor interface
to which viruses bind. Decoys can achieve similar or even higher affinity
than human protein receptors by stabilizing the binding interface.
At an optimal concentration, decoys can outcompete viral interaction with patients' cells.
https://science.sciencemag.org/content/early/2020/11/04/science.abe0075
The linoleic acid (LA, an essential fatty acid) binding pocket
within the S protein and the multinodal LA signaling axis
may represent excellent therapeutic intervention points to treat SARS-CoV-2 infections.
https://science.sciencemag.org/content/370/6517/725
A nasal spray that blocks the virus worked well in a study that tested it on ferrets.
It contains a lipopeptide (a cholesterol particle linked to a chain of amino acids,
the building blocks of proteins) matching a stretch of amino acids
in the SARS-CoV-2 spike protein.
https://www.biorxiv.org/content/10.1101/2020.11.04.361154v1
SARS-CoV-2 mutation in Danish mink [ closing the barn door after... ]
The Danish government has ordered the slaughter of all farmed mink in the country
after the reported discovery of a mutant form of coronavirus in the animals.
It has already spread to humans.
[ other delayed door closings ] More state officials announce restrictions
In Connecticut, new measures are going into effect Friday.
Rhode Island Gov. Gina Raimondo announced new restrictions taking effect Sunday
https://www.cnn.com/2020/11/06/health/us-coronavirus-friday/index.html
EUA for Ortho VITROS SARS-CoV-2 Antigen Mass-Scale Test; compared to PCR,
Ortho's test may be better able to identify individuals with COVID-19 who are infectious.
Swab samples for Ortho's SARS-CoV-2 antigen test can be collected in bulk, stored at
room temperature for up to 24 hours or 48 hours if refrigerated, and contrary to PCR tests,
which can take hours to obtain results, run on Ortho's high-throughput VITROS Systems,
which are capable of processing up to 130 antigen samples per hour.
96% sensitivity, 99% Specificity
More on University of Washington's vaccine
that fuse 60 copies of SARS-CoV-2's spike protein to
exterior surface of each two-component protein nanoparticle I53-50.
https://www.nature.com/articles/d41586-020-00502-w
Age-severity matched cytokine profiling reveals specific signatures in COVID-19 patients
Defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-a -
positively correlate with age, longer hospitalization, and a more severe form of the disease.
https://www.nature.com/articles/s41419-020-03151-z
"region-to-region reproductive number"
Since it is impossible to model all the details of real-world systems,
identifying large-scale behaviors is necessary to determine which details matter and how.
COVID-19 parameters for these large-scale behaviors include
the average size of an outbreak within a region and
the transmissibility of the outbreak among regions.
These two parameters determine whether, among a collection of regions (e.g., a country),
there is exponential epidemic spread until saturation or decay until elimination.
https://www.nature.com/articles/s42005-020-00470-7
"We observed a worrying trend of an approximately 3% annual increase in mortality
due to acute respiratory failure in the U.S. in the last five years.
Additionally, we noted that deaths due to ARDS, a fatal lung condition,
which had been declining in the early 2000s, has now become stagnant."
ARDS is the primary cause of death among patients with COVID-19.
https://medicalxpress.com/news/2020-11-acute-respiratory-failure-mortality-states.html
An in-depth picture of the pulmonary landscape in COVID-19 (10 patients),
pandemic H1N1 (pH1N1) influenza (5) and uninfected control patients (4).
SARS-CoV-2 was non-uniformly distributed in lungs with few areas of high viral load
and these were largely only associated with an increased type I interferon response.
A very limited number of genes were differentially expressed between the lungs of influenza
and COVID-19 patients. Specific interferon-associated genes (including IFI27) were identified
as candidate novel biomarkers for COVID-19 differentiating this COVID-19 from influenza.
https://www.medrxiv.org/content/10.1101/2020.11.04.20225557v1
Among 157,544 participants tested,
the risk of hospitalization in comparison to a 20-year-old of normal BMI:
210% for the same age with BMI between 35-40 kg/m2
533% for a 55-year-old with normal BMI
1120% for a 55-year-old with BMI between 35-40 kg/m2
Compared to blood group O, blood group A has 115% risk of contracting COVID-19,
but no appreciable difference in severity.
https://www.medrxiv.org/content/10.1101/2020.11.05.20226100v1
Phase 1 CoVLP COVID-19 vaccine candidate trial using recombinant virus-like particles
produced by a close relative of tobacco indigenous to Australia.
All formulations were generally well-tolerated in 180 subjects.
The addition of an adjuvant was needed for both antibody and cellular responses
at most CoVLP dose levels, and changes were most pronounced after the second dose.
When administered with AS03, even the 3.75 microgram CoVLP dose elicited neutralizing antibody titers
that were ~10-times higher than those observed in individuals recovering from COVID-19
as well as consistent and balanced IFN-gamma and IL-4 responses. (58 pages)
https://www.medrxiv.org/content/10.1101/2020.11.04.20226282v1.full.pdf
Overall, data suggests that a sudden loss of sense of smell is a more common early symptom
of COVID-19 than fever across all age groups. It is a 20-fold better predictor of a positive test
for COVID-19 in younger people and a 13-fold better indicator in older people
than any other symptoms.
There is little scientific evidence that temperature checks reliably detect COVID-19;
57% who test positive never develop a fever.
65% of adults who tested positive for COVID-19 reported a loss of sense of smell.
https://theconversation.com/should-we-all-be-using-sniff-tests-to-screen-for-covid-19-149553
new immune-cell activation mechanism discovered
The short endosomal protein interferon-inducible transmembrane protein 3 or IFITM3
is a central amplifier to supercharge activation of immune cells.
While this mechanism helps immune cells to fight infections,
cancer cells also use the mechanism for activation and explosive growth.
https://medicalxpress.com/news/2020-11-uncover-mechanism-immune-cell.html
SARS-CoV-2-infected children have distinctly different antibody response that do adults
Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies,
as well as anti-nucleocapsid (N) IgG antibody,
while children had reduced breadth of anti-SARS-CoV-2-specific antibodies,
predominantly generating IgG antibodies specific for the S protein
but not the N protein, along with reduced neutralizing activity.
https://www.nature.com/articles/s41590-020-00826-9
How likely you are to become infected with coronavirus can depend on
how much virus you inhale, where those particles land in your respiratory tract,
and even the weather.
The upper part of the throat behind the nasal passages and above the esophagus and
voice box, known as the nasopharynx, is the most accessible seeding zone for the virus.
Droplet sizes most likely to reach that zone were larger than expected.
"Most masks would block out these droplet sizes, so wearing a mask is very useful"
"The droplets being inhaled after dehydration in the external air carry a larger viral load"
Typically, an inhaled viral infection requires 1,950 to 3,000 virus particles,
but 300 virus particles are the estimated threshold for COVID-19 infection.
https://medicalxpress.com/news/2020-11-dose-coronavirus-infection.html
Consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening,
unless schools and non-essential workplaces remain closed.
Up to half the population could be infected with full workplace reopening;
non-essential business closures reduced median cumulative infections by 82%.
Intermediate reopening interventions identified no win-win situations.
https://www.medrxiv.org/content/10.1101/2020.11.03.20225409v1
Small molecule MP1032, a phase-pure anhydrous polymorph of
5-amino-2,3-dihydro-1,4-pthalazinedione sodium salt
that exhibits good stability and bioavailability,
is a promising option for prevention/treatment of SARS-CoV-2-induced cytokine storm
https://www.medrxiv.org/content/10.1101/2020.11.03.20216580v1
Rapid COVID-19 tests are being deployed by the millions across the nation.
The COVID-19 pandemic has been a data horror story from the beginning.
Without significant changes, which are unlikely, rapid tests will make this data deficit worse.
Thousands upon thousands of rapid testing sites nationwide are beginning to operate
outside of laboratory facilities and are not equipped to comply with state
and federal reporting regulations.
https://www.statnews.com/2020/11/05/rapid-covid-19-tests-hidden-public-health-hazard/
A nice article about Novavax and its NVX-CoV2373 SARS-CoV-2 vaccine candidate
Made by moth cells harnessed to crank out the virus' spike protein,
"it's the only vaccine I've seen out of all the candidates that are further down the pipeline
that actually had no viral replication in the nasal swabs of vaccinated animals,"
Oct 2019: "Good ideas. Bad management. The company will probably die soon."
Novavax has focused on making vaccines for more than 20 years
but has not yet brought one to market. It has produced a promising flu vaccine
aimed at older adults, which successfully ended its phase 3 trial in March.
Novavax mostly relies on contract manufacturers;
manufacturing delays slowed launch of its late stage North American trial.
"I think the vaccine is going to be efficacious,
but you put that 2 billion dose task in front of a small company, it's a huge uphill task."
The Serum Institute of India, a veteran vaccine maker that is the world's largest,
is helping Novavax expand production at the 14,000-square-meter Czech facility, plus manufacturing
an additional billion doses itself, in India, for low- and middle-income countries.
Gale Smith, Novavax's chief scientist, co-invented the system using moth cells
to make the protein sub-unit in vast quantities. Nita Patel and her all-female crew
developed and conducted the sophisticated tests to verify the vaccine works as intended.
In February, Patel's team tested more than 20 engineered variants of the protein,
identifying the version most likely to elicit a protective immune response.
Now, she's characterizing details of that protein,
identifying the precise locations where neutralizing antibodies vigorously bind to it,
and creating a test to ensure the spike is consistent from one manufacturing plant to another.
A semi-split inactivated SARS-CoV-2 vaccine was designed to stimulate the immune system
not only for the spike (S) protein but also the envelope, membrane and nucleocapsid proteins.
Very early onset of antibodies was observed in mize,
with significantly higher levels of neutralizing antibodies
detected for doses injected intradermally than intramuscularly.
https://www.biorxiv.org/content/10.1101/2020.11.03.366641v1
U.S. study "found a significant negative effect between increasing humidity
and new cases of COVID-19 in most regions, particularly in the period from March to July.
The effect was greater in regions with generally lower humidity in the Western, Midwest, and Northeast regions"
https://www.medrxiv.org/content/10.1101/2020.10.30.20223446v1.full.pdf+html
Real-life clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best (47%).
Relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for
in clinical decision making, epidemiological interpretations
and when using RT-PCR as a reference for other tests.
https://www.medrxiv.org/content/10.1101/2020.11.01.20223107v1.full.pdf
Abbott BinaxNOWTM COVID-19 rapid antigen test virus detection performance
was evaluated among persons, regardless of symptoms,
at a San Francisco public plaza site of ongoing community transmission.,
resulting in 14/15 sensitivity and 862/863 specificity, relative to RT-PCR.
https://www.medrxiv.org/content/10.1101/2020.11.02.20223891v1
A new hybrid computer model for COVID-19 dynamics
using both an age-structured mathematical model and spatio-temporal model.
The age-structured mathematical model uses separate SIRD models for children and adults.
The spatial model examines a circle of day and night (with one-hour resolution)
and three main locations (work / school or home) for every individual.
[ Their Table 1 includes infection rates: 27% adult-to-child, 0% child-to-adult,
30% adult-to-adult and child-to-child ] (28 pages)
https://www.medrxiv.org/content/10.1101/2020.11.02.20224584v1.full.pdf
A mathematical simulation to evaluate the effectiveness of quarantine and testing for arriving travelers,
alone and in combination, across a variety of scenarios
found that quarantine was more effective than testing alone, even for quarantine as short as two days,
and the value of adding testing to quarantine diminished for longer quarantine durations.
Testing was most effective if performed near the end of quarantine. (15 pages)
https://www.medrxiv.org/content/10.1101/2020.11.02.20224568v1.full.pdf
Without ever specifying exactly what "attack rate" means, this 30 page report
analyzed the crap out of 112 enrolled households with 291 participants in Bergen, Norway.
All households already had at least one positive case.
Serology identified a significantly higher number of infected members than RT-PCR.
Attack rates were equally high in children (43%) and young adults (46%),
but highest among household members aged =60 years (72%).
The attack rate was 16% in asymptomatic household members
and 42% in RT-PCR negative household members.
Older adults generally had higher antibody titres than younger adults.
The risk of household transmission was higher when the index case had fever
or dyspnoea during acute illness but not associated with cough.
https://www.medrxiv.org/content/10.1101/2020.11.02.20224485v1.full.pdf
Swiss SARS-CoV-2 infections among 4,524 household members five years and older
from 2,267 households: The chance of being infected
by a single SARS-CoV-2 infected household member was 17.2%, compared to 5.1% from an outsider.
Household infection risk increased from 7.5% among children 5-9 to 30% for those over 65.
Working-age adults (20-49 years) had the highest extra-household infection risk.
Seropositive household members not reporting symptoms
had 74.8% lower odds of infecting another household member
compared to those reporting symptoms,
accounting for 19.6% of all household infections.
https://www.medrxiv.org/content/10.1101/2020.11.04.20225573v1
Space-Time COVID-19 Bayesian SIR modeling in South Carolina
using data from the New York Times GitHub repository
25% asymptomatic rate better fit later and smoothed 3 day average data
Poverty better explains risk variation at the county level. (19 pages)
https://www.medrxiv.org/content/10.1101/2020.11.03.20225227v1.full.pdf
Selection, biophysical and structural analysis of synthetic nanobodies
that effectively neutralize SARS-CoV-2.
In particular, sybody 23 (Sb23) binds to recombinant RBD as well as to the prefusion
spike glycoprotein with high affinity and shows very potent neutralization activity.
https://www.nature.com/articles/s41467-020-19204-y
Heparan sulfate assists SARS-CoV-2 in cell entry
and can be targeted by approved drugs in vitro
Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while
Sunitinib and BNTX disrupt the actin network
to indirectly abrogate HS-assisted viral entry.
Drugs of the two classes can be combined to generate a synergized activity
against SARS-CoV-2-induced cytopathic effect.
https://www.nature.com/articles/s41421-020-00222-5
Pfizer intends to handle distribution of its COVID-19 vaccine itself
after the federal government's initial distribution to priority populations is completed.
Because its mRNA vaccine must be stored at minus 94 degrees Fahrenheit,
the plan includes shipping containers that can keep doses at that temperature for 10 days.
Bioengineered Lactobacillus - a safe, widely used bacteria best
recognized for its role in fermenting yogurt and cheese - could deliver antigens,
the vaccine component that triggers an immune response,
directly to the mucosal tissues of the nose and mouth.
This site-specific strategy may provide more robust protection against COVID-19
than an injected vaccine because it would more closely mimic a natural COVID-19 infection,
producing antibodies and immune cells in the key locations where the virus enters.
https://medicalxpress.com/news/2020-11-nasal-needle-free-covid-vaccine.html
COVID-19 blood clots attributed to autoimmune antibody circulating in blood
"We've discovered a new mechanism by which patients with COVID-19 may develop blood clots."
"Half of the patients hospitalized with COVID-19 were positive
for at least one of the autoantibodies"
"We don't yet know what is triggering the body to produce these antibodies"
A randomized clinical trial called DICER is testing a well-known anti-clotting agent,
dipyridamole, in COVID-19 patients to determine its effectiveness in reducing excessive blood clots.
https://stm.sciencemag.org/content/early/2020/11/02/scitranslmed.abd3876
Events where one person infects more than 6 others
are much more common than would be expected if COVID-19 transmission rates
followed statistical distributions commonly used in epidemiology.
https://www.pnas.org/content/early/2020/10/30/2018490117
Death rates for COVID-19 patients under 65
correlate more directly to underlying SARS-CoV-2 transmission rates.
"Our model shows that the number of COVID-19 deaths by age, in people under 65 years old,
is highly consistent across countries
and likely to be a reliable indicator of the number of infections in the population."
https://www.nature.com/articles/s41586-020-2918-0
Elicitation of potent neutralizing antibody responses
by computationally designed two-component self-assembling protein
nanoparticle multivalent receptor-binding domain-based vaccines for SARS-CoV-2
https://www.cell.com/cell/pdf/S0092-8674(20)31450-1.pdf
Calculating SARS-CoV-2 transport properties using a particle model from tiny beads,
and then applying the laws of fluid physics to each and every bead. Since the virus
cannot move itself, it relies on the random thermal motion of its fluid surroundings
to rotate and align its spikes with its target on a cell
https://aip.scitation.org/doi/10.1063/5.0031875
A cheaper and faster surrogate virus neutralization test correlated strongly with
SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus vector-based neutralization assay,
and also does not require any biosafety labs. This could make it important
for evaluating the prevalence of neutralizing antibodies in a population and
also for identifying promising plasma donors for successful passive antibody therapy.
https://www.nature.com/articles/s41423-020-00573-9
A severe COVID-19 patient was successfully treated with
human recombinant soluble angiotensin-converting enzyme-2 (hrsACE2).
Notably, the use of hrsACE2 did not impede the generation of neutralizing antibodies,
leading to a significant clinical improvement of the treated patient.
https://www.nature.com/articles/s41392-020-00374-6
The fastest way to identify potent, neutralizing human monoclonal antibodies
against SARS-CoV-2. [?] Pitt's Center for Antibody Therapeutics (CAT) over the last
several years built multiple libraries containing a total of 1 trillion human antibodies.
Ab1 was identified in 6 days. "The main differences between our rapid 'panning' method
and the 'screening' process used by most companies this year to discover antibodies against
SARS-CoV-2 is that panning is much quicker than screening,
and we don't have to wait for infected patients to recover and make antibodies"
https://www.pnas.org/content/pnas/early/2020/10/30/2010197117.full.pdf
Ab8, a smaller-sized but very potent antibody was isolated from their antibody libraries last month.
[ why so long to find? ] Ab8 isn't as far along in development as Ab1,
but being a smaller molecule, it could potentially be administered subcutaneously
or even through inhalation, which might make it more practical for widespread use.
Phase II Clinical trial for Evaluation of BCG as potential therapy for COVID-19
Primary endpoints were favorable prognosis of COVID-19 as deduced from resolution of pneumonia,
viremia and secondary outcome were enumeration of ICU admissions, duration thereof and mortalities.
Results Both primary and secondary endpoints were significantly improved
in the groups receiving BCG in addition to standard care.
https://www.medrxiv.org/content/10.1101/2020.10.28.20221630v1
SARS-CoV-2 detection by nasal strips: a superior tool for surveillance of pediatric populations.
The agreement between nasal strip samples and
pooled nasopharyngeal swab and throat swab (NPSTS)
was 94.44% and 100% for NPSTS positive and negative samples.
https://www.medrxiv.org/content/10.1101/2020.10.28.20220673v1.full.pdf+html
Association of COVID-19 RT-qPCR test false-negative rate with patient age, sex
and time since diagnosis (23 pages)
In the first few days following diagnosis, when results are critical for quarantine decisions,
RT-qPCR testing is more reliable (10.7% false negative) than previously reported.
Yet the reliability of the test result is reduced in later days (39%)
as well as for women and younger patients, where the viral loads are typically lower.
https://www.medrxiv.org/content/10.1101/2020.10.30.20222935v1.full.pdf+html
Problematic oversight of EUAs for lab developed tests
EUA laboratory developed tests, known as LDTs, use the same basic PCR technology
to identify genetic material from the coronavirus in patient swabs,
but their performance can vary widely.
The FDA has granted emergency authorization to more than 200 diagnostic tests,
and LDTs may account for more than half of tests in use.
This summer, the Department of Health and Human Services
directed the FDA to stop requiring emergency authorization for this segment of the testing market.
The Centers for Medicare and Medicaid Services retained oversight of the labs,
but it ensures only that labs meet quality standards, not that specific tests work.
The decision meant the FDA has no way to track problems with COVID-19 LDTs
- including false-positive or false-negative results - or even which labs are marketing these tests.
Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations
The best neutralizing antibody targets the host receptor binding site of the virus spike protein,
and its tetravalent version can block virus infection
with a potency that exceeds that of bivalent IgG by an order of magnitude.
https://www.biorxiv.org/content/10.1101/2020.10.31.362848v1.full.pdf+html
Boceprevir, calpain inhibitors II and XII, and GC-376 have broad-spectrum antiviral activity
in cell culture against not only SARS-CoV-2, but also SARS-CoV, MERS-CoV,
as well as human coronaviruses (CoVs) 229E, OC43, and NL63.
https://www.biorxiv.org/content/10.1101/2020.10.30.362335v1.full.pdf+html
Seven different 'disease forms' identified in mild COVID-19
(1) flu-like symptoms (with fever, chills, fatigue and cough),
(2) (common cold-like symptoms (with rhinitis, sneezing, dry throat and nasal congestion),
(3) joint and muscle pain,
(4) eye and mucosal inflammation,
(5) lung problems (with pneumonia and shortness of breath),
(6) gastrointestinal problems (including diarrhea, nausea and headache) and
(7) loss of sense of smell and taste and other symptoms.
https://medicalxpress.com/news/2020-11-disease-mild-covid-.html
Vancouver-based Algernon Pharmaceuticals continues phase 2b/3 trial
of an orally delivered drug, NP-120 (ifenprodil), as a late-stage COVID-19 treatment.
Ifenprodil was originally developed in the 1990s by Sanofi to treat peripheral circulatory disorders
and it is still used in generic form in Japan.
Hong Kong-based Prenetics has acquired Oxsed Technologies,
a UK company that has developed a rapid COVID-19 test based on research at the University of Oxford.
The CE-marked COVID-19 test is currently in use at a rapid testing facility in London's Heathrow airport for pre-departure passengers.
It can use nasopharyngeal and oropharyngeal swabs as well as saliva and mouthwash samples.
The test, which uses reverse transcription loop-mediated isothermal amplification (RT-LAMP) technology,
can deliver results in 15 to 30 minutes.
Prenetics plans to ramp up production of the test for global distribution.
Simtomax CoronaCheck, a serology rapid diagnostic test (RDT)
for the detection of IgG and IgM against SARS-CoV-2,
has 92% sensitivity and 97% specificity overall
both increasing for samples more than 15 days post-symptoms.
https://www.medrxiv.org/content/10.1101/2020.10.28.20219667v1.full.pdf
Remote fingerstick blood collection for SARS-CoV-2 antibody testing
using Neoteryx Mitra at-home collection device and Roche Elecsys laboratory assay
were equivalent to conventional EUA serological tests
used to confirm the development of humoral immunity after infection or vaccination.
https://www.medrxiv.org/content/10.1101/2020.10.27.20221028v1.full.pdf+html
Except for residents from Connecticut, New Jersey, or Pennsylvania,
travelers to New York State will be required to obtain a negative COVID-19 test
within three days before arriving in the state. The policy goes into effect Wednesday.
Once in New York, travelers will be required to quarantine for 3 days before getting another test.
If second tests are negative, travelers will no longer be required to quarantine.
https://www.bloomberg.com/news/articles/2020-10-31/new-york-sets-3-day-quarantine-for-visitors-who-test-negative
SC subsidizing alleged COVID-19 rapid test startup
Originally launched in 2019 at a Wyoming tech incubator
as a defense contractor by ex-lobbyists, Vigilent Labs is now colluding
with Leinco (a legitimate but minor antibody, protein and reagent provider)
and SeroClinix ( a veterinary diagnostics supplier)
on a $105M, 400 employee plant at the former Navy base in North Charleston.
In the U.S. only a few companies have been granted FDA EUA to sell rapid diagnostic tests,
and most of these tests are manufactured offshore.
Lienco has COVID-19 rapid test intellectual property
from Vanderbilt Vaccine Center. for which I find no trial data, much less FDA EUA.
Current FDA EUAs are issued for COVID-19 rapid tests outside laboratories to:
Abbott Diagnostics, Access Bio, Assure Tech, LumiraDx, Quidel
FDA's EUA for the LumiraDx rapid test requires their laboratory instrument
In 101 households with an initial COVID-19 case,
infection spread within 14 days to 102 of 191 household members.
In 14 households with initial patients under age 18,
children infected 53% of their contacts, and teens infected 38% of contacts.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e1.htm?s_cid=mm6944e1_w
COVID-19 cases are surging in every swing state
In the 13 states deemed competitive by the Cook Political Report,
the weekly average of new cases reported daily has jumped 47% over the past 2 weeks
PRAK-03202, the world's first triple antigen virus-like particle COVID-19 vaccine candidate
The design and manufacture of the PRAK-03202 vaccine candidate
represent a plug and play process in which the three-target antigen
(S, E, and M) sequence was inserted into a highly characterized
S.cerevisiae based D-CryptTM platform (Premas Biotech).
Immunoblot analysis confirmed the expression of the SEM proteins
using commercially available antibodies.
The co-expression of S, E and M was further confirmed by mass spectrometry.
PRAK-03202 was successfully tested on mice.
https://www.biorxiv.org/content/10.1101/2020.10.30.360115v1.full.pdf
9 million U.S. COVID-19 cases [ officially, so probably 50 million ] with 1% Thursday
Over 1/2 million cases this week, up 42% over 2 weeks;
new cases are increasing in 42 states.
[ GE: 'Progress Is Our Most Important Product' ]
About 20% of grocery store workers had COVID-19, and most didn't have symptoms
Workers who dealt with customers were 5 times as likely to test positive for COVID-19
3 / 4 of those who tested positive had no symptoms.
91% said they wore a face mask at work, and 77% said they also wore masks outside of work.
About 2/3 said they were able to practice social distancing consistently on the job.
https://www.cnn.com/2020/10/29/health/grocery-workers-increased-covid-19-risk-wellness/index.html
mostly effective before symptoms merit hospitalization
In a trial, 0.9% of COVID-19 patients treated with LY-CoV555 plus LY-CoV016
in emergency rooms were eventually hospitalized, compared to 5.8% of the placebo group.
$1250 per dose plus $1000 intravenous infusion charge
want storage at -20C in 50% glycerol
The federal government plans to buy and distribute 300,000 doses of Eli Lilly's
[ Presumably, about that many Trump donors have access to personal IVs ]
On Thursday, 9 states reported record high new COVID-19 cases:
Illinois, Indiana, Maine, Michigan, Minnesota, New Mexico, North Carolina, North Dakota and Ohio.
88,521 new cases were reported in the U.S.
https://www.cnn.com/2020/10/30/health/us-coronavirus-friday
The Lancet has become the latest science journal to urge Americans
to vote for change in next week's presidential election.
It urges voters to "reject the stagnancy of complacency,
to exchange a view bereft of intention with a vision of progress, and
to rejoin the global community in the pursuit of a more equitable and sustainable future".
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32260-1/fulltext
In an online survey of NY health care workers,
51.5% worked directly or in close physical contact with COVID-19 patients.
Of those tested for COVID-19, 27.3% were positive.
57.6% reported a negative impact of the COVID-19 efforts on their mental health.
https://www.medrxiv.org/content/10.1101/2020.10.29.20222372v1.full.pdf+html
A dynamic compartmental model of COVID-19 transmission in NY, TX, FL, CA
To suppress an epidemic in these states if face mask use is reduced 50%:
* a (weak) vaccine that is 50% effective would require coverage of 55-94%;
* a (moderate) vaccine that is 80% effective requires 32-57% coverage.
In contrast, if face mask usage stops completely:
* a moderate vaccine requires 48-78% coverage;
* a 100% effective vaccine requires 33-58% coverage;
* a weak vaccine does NOT suppress the epidemic, and further major outbreaks occur.
https://www.medrxiv.org/content/10.1101/2020.10.28.20221234v1.full.pdf+html
Masks and variolation
Variolation was first used to immunize individuals against smallpox
with material taken from a patient or a recently variolated individual,
in the hope that a mild, but protective, infection would result.
In an outbreak on a closed Argentinian cruise ship,
where passengers were provided with surgical masks and staff with N95 masks,
the rate of asymptomatic infection was 81% (as compared with 20% in earlier cruise ship outbreaks without universal masking).
In two recent outbreaks in U.S. food-processing plants,
where all workers were issued masks each day and were required to wear them,
the proportion of asymptomatic infections among the more than 500 people who became infected was 95%,
with only 5% in each outbreak experiencing mild-to-moderate symptoms.
https://www.nejm.org/doi/full/10.1056/NEJMp2026913
Spying on COVID-19
AI model detects asymptomatic COVID-19 infections through cellphone-recorded coughs
It accurately identified 98.5% of coughs from people who were confirmed to have COVID-19,
including 100% of coughs from asymptomatics who reported they did not have symptoms but had tested positive for the virus.
https://medicalxpress.com/news/2020-10-artificial-intelligence-asymptomatic-covid-infections.html
"piecewise linear model" offers public health officials a "simple and effective way
to study the dynamics of the epidemic and to generate accurate
one-week and two-week ahead forecasts of confirmed cases/deaths of COVID-19"
https://medicalxpress.com/news/2020-10-covid-cases-impact-health.html
Study: more than 90% of individuals infected with mild-to-moderate COVID-19
mount a robust antibody response that is relatively stable for at least 5 months.
[ no new data on asymptomatic cases,
for which 40% have no antibody response after 8 weeks, according to earlier papers ]
https://science.sciencemag.org/content/early/2020/10/27/science.abd7728/tab-pdf
Prolonged COVID-19 infectivity
16.7% of recovered patients had PCR positive recurrences 1 to 3 times,
despite being in strict quarantine. Younger patients with
mild pulmonary respiratory syndrome had higher risk of PCR positivity recurrence.
https://www.nature.com/articles/s41598-020-75629-x
Mask material survey
N95 masks were highly effective, although a reusable HEPA vacuum bag
actually exceeded the N95 performance in some respects.
"N95 masks are much easier to breathe through
than any fabric combinations with similar levels of filtration."
https://bmjopen.bmj.com/content/10/9/e039424.full
NY Times: record cases; states second-guessing FDA; Pfizer trial results slow in coming
Fauci: "Unfortunately, we're right now in the middle of what's going to be referred to
... as the mother of all outbreaks over the last hundred years,
And we're not even close to being finished with it yet. [40:00/52:57]
...
The big open question is durability of the [vaccine] protection"
At least 2022 before masks become optional
[ 53 minute video; Fauci starts @ 2:53; Q&A starts @ 8:25, so really only about 5.5 minutes ]
discussion @ 41:00 that anti-viral (monoclonal antibody) therapies are effective
very early (first couple of days) in the course of infection,
before "aberrant inflammatory response that gets people into trouble"
https://www.youtube.com/watch?v=I5q2WegIeBM
Human interest story: Akiko Iwasaki tackles SARS-CoV-2, after 20 years studying viruses
Iwasaki has long advocated for female and minority scientists on Twitter, where she has 80,000 followers.
Iwasaki's husband, Ruslan Medzhitov, is also a well-known Yale immunologist
(they discuss COVID-19 while walking their dog)
"I'm thinking, 'I don't know what I'm doing here.'" 'Basic research is what I am doing when I don't know what I am doing.' - Wernher von Braun
COVID-19 can take hold in the salivary glands where it replicates, and in some cases,
leads to prolonged disease when infected saliva is swallowed into the gastrointestinal tract
or aspirated to the lungs where it can lead to pneumonia.
https://www.medrxiv.org/content/10.1101/2020.10.26.20219089v1
Medical costs of keeping the U.S. economy open during COVID-19
(1) Without mitigation, total medical costs would be 5% of the U.S. GDP;
(2) a lockdown of just 2 months, if done early in the epidemic and with sufficient compliance,
could have reduced the medical costs by more than 90%;
(3) if 90% compliance could be achieved, then even a 45 day lockdown period
would have been enough to contain the epidemic and medical costs;
(4) if Hospital Referral Regions (HRRs) do not share hospital beds with other HRRs,
a significant deficit of beds will cause costs to skyrocket, through increased deaths.
However, if HRRS share beds with their neighboring HRRs,
bed-deficits and additional deaths could be reduced to almost zero;
(5) costs are most sensitive to the duration of the stay-home order.
https://www.nature.com/articles/s41598-020-75280-6
Optimal COVID-19 quarantine and testing strategies
A 13-day quarantine with testing on entry,
a nine-day quarantine with testing on exit, or
an eight-day quarantine with testing on both entry and exit
each provides equivalent or lower probability of post-quarantine transmission
compared to a 14-day quarantine with no testing..
Based on 4,040 SARS CoV-2 RT-PCR tests,
an exit test 96 hours after start of quarantine for an offshore oil rig population
identified all known asymptomatic cases that previously tested negative at entry.
https://www.medrxiv.org/content/10.1101/2020.10.27.20211631v1
Why North and South Dakota are suffering the worst COVID-19 epidemics in the U.S.
COVIDcast, a project from Carnegie Mellon University that tracks real-time COVID-19 data,
shows that North and South Dakota have some of the lowest levels of uptake in the U.S.
for both social distancing and masking. South Dakotans are the sixth most likely and
North Dakotans are the eighth most likely, out of the 50 states plus Washington, DC, and Puerto Rico,
to leave their homes for six or more hours a day. South Dakotans and North Dakotans
are also among the least likely - 50th and 49th, respectively, out of all 50 states plus DC - to wear masks.
Breathalyzer-style testing for COVID-19
near-patient gas chromatography-ion mobility spectrometry (GC-IMS)
sensitivity/specificity 82.4%/75% in a population of 21/33 infected
and 90%/80% in a population with 10/65 having COVID-19.
A 7-hour flight has been linked to 59 coronavirus cases
Thirteen of the 49 passengers onboard tested positive for the novel coronavirus,
even though the flight was only 17% full.
Those 13 passengers went on to infect 46 more.
Masks were utilized by 9 of those 13 infected passengers,
with one child not wearing a mask and 3 passengers' mask use "unknown"
"Four of the flight cases were not seated next to any other positive case,
had no contact in the transit lounge,
wore face masks in-flight and would not be deemed close contacts"
Symptoms began to appear in the earliest cases two days after the flight,
and the latest case linked to the plane experienced symptoms 17 days after the flight.
Eli Lilly LY-CoV555 NIH-sponsored trial as severe COVID-19 therapeutic halted; unlikely helpful.
Safety concerns have been dismissed; Lilly-sponsored LY-CoV555 trial for mild cases continues.
The announcement is an indication that monoclonal antibodies may only work
if given early in the course of a coronavirus infection,
before the virus has had a chance to penetrate deep into the lungs and cause serious damage.
Here's what you need to have on hand in your pantry, freezer, medicine cabinet and more
to limit errands and in case of sickness, quarantine or disaster this season.
"First, the virus that causes COVID-19 is a coronavirus
and other coronaviruses spread more in winter months.
Second, in winter months, the air is less humid.
Particles that carry the virus can linger in the air for longer.
Also, our nasal membranes are drier and more vulnerable to infection."
[ other sources report SARS-CoV-2 itself surviving longer at higher humidities ]
https://www.cnn.com/2020/10/27/health/how-to-prepare-for-covid-surge-wellness/index.html
Modeling of SARS-CoV-2 transmission in confined spaces suggests
aerosol microdroplets that linger in the air longest after we talk, cough, or sneeze,
do not appear to be extremely efficient at spreading it.
The researchers acknowledge the study's findings are "necessarily subjective."
https://aip.scitation.org/doi/10.1063/5.0027844
New mathematical modeling 'shows' partial immunity combined with social distancing
would significantly reduce SARS-CoV-2 mortality rates, if immunity lasts for about one year.
https://mbio.asm.org/content/11/5/e02617-20
Massive genome-scale, loss-of-function CRISPR screen systematically
knocked out genes in the human genome to identify which are required by SARS-CoV-2
and that confer resistance to COVID-19 when suppressed.
[ these were presumably tested singly; combinations could take enormously long ]
Top-ranked genes are clustered into a handful of protein complexes, including
vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K.
Many of these protein complexes are involved in trafficking proteins to and from cell membranes.
https://www.cell.com/cell/pdf/S0092-8674(20)31394-5.pdf
PSA: Yahoo click-bait about Fauci and early COVID-19 vaccines not blocking viruses is BS.
Indeed, Fauci "would settle for" vaccines that prevent symptoms,
but that involves antibodies resisting spread, which reduces shedding and contagion.
There are certainly some approaches designed to more specifically disable
SARS-CoV-2 spike proteins' ability to invade cells.
Video about mRNA vaccines
Saliva vs nasopharyngeal swab (NPS) testing
SARS-CoV-2 RNA was detected in 32.2% (97/300) of the individuals using the TaqPath COVID-19 Combo Kit (Thermo Fisher).
The overall concordance for saliva and NPS was 91.0% (273/300) and 94.7% (284/300), respectively.
The positive percent agreement (PPA) for saliva and NPS was 81.4% (79/97) and 89.7% (87/97), respectively.
Saliva detected 10 positive cases that were negative by NPS.
In symptomatic and asymptomatic pediatric patients not previously diagnosed with COVID-19,
the performances of saliva and NPS were comparable (PPA: 82.4% vs 85.3%).
The overall PPA for adults were 83.3% and 90.7% for saliva and NPS, respectively,
with saliva detecting 4 cases less than NPS. However,
saliva performance in symptomatic adults was identical to NPS (PPA of 93.8%).
With lower cost and self-collection capabilities,
saliva can be an appropriate alternative sample choice to NPS for detection of SARS-CoV-2 in children and adults.
https://www.medrxiv.org/content/10.1101/2020.10.25.20219055v1
The number of Americans currently hospitalized with COVID-19 has risen by 12,000
over the last month, reaching 41,753 on October 25, according to the COVID Tracking Project.
Some hospitals are drawing up plans to ration care if they have more patients than beds,
the kind of worst-case scenario they'd been hoping to avoid.
Every state except Hawaii, Delaware, and Louisiana (and Washington, DC)
saw their case numbers rise over the last two weeks, according to Covid Exit Strategy.
20 states have more than 70% of their ICU currently occupied
If, as expected, Utah hospitals activate their emergency surge capacity plans,
then in the event that two patients' conditions are equal,
the young get priority over the old, since older patients are more likely to die.
Hospitals in Kansas City, Missouri, are reportedly turning away ambulances
because they don't have any beds available,
and urban hospitals warn they may not be able to accept overflow patients from rural areas.
(Hospitalizations in Missouri reached a new record last week.)
https://www.vox.com/21534195/covid-19-cases-hospital-capacity-el-paso
A novel model-agnostic Bayesian optimization approach for learning model parameters
from observed data that generalizes to multiple application-specific fidelity criteria.
Empirical results demonstrate the efficacy of the proposed approach
with SEIR-like compartmental models on COVID-19 case forecasting tasks.
https://www.medrxiv.org/content/10.1101/2020.10.19.20215293v1.full.pdf
Vaccine tracker provides real-time updates on progress in developing a COVID-19 vaccine
20/19/11 in phase 1/2/3 trials, respectively
https://covid19.trackvaccines.org/vaccines/
... after correction for confounding variables, most notably testing rates, there was
no association between BCG vaccination policy and COVD-19 spread rate or percent mortality
[sigh]
https://www.nature.com/articles/s41598-020-75491-x
Utah's hospitals prepare to ration care as COVID-19 patients flood their ICUs
Greg Bell, president of the Utah Hospital Association, said 'It's gonna happen.
We're going to be back here asking for crisis standards.'
At least two Utah hospitals have opened overflow ICUs this month.
Utah has long planned to open a field hospital at the Mountain America Expo Center in Sandy
if necessary., but qualified staffing is an issue.
https://www.sltrib.com/news/2020/10/25/with-coronavirus-cases/
Fauci: "We will know whether a vaccine is safe and effective by the end of November,
beginning of December," but vaccination of a "substantial proportion of the population"
so there could be a "significant impact on the dynamics of the outbreak"
may not be possible until the second or third quarter of 2021.
https://www.cnn.com/2020/10/25/us/covid-vaccine-fauci/index.html
Decline of neutralizing antibody responses in the 3 months following SARS-CoV-2 infection
Waning was detected at 40 days post onset of symptoms (POS)
[ 2 vaccine jabs every 2 months? ]
Requirements for the containment of COVID-19 disease outbreaks
through periodic testing, isolation, and quarantine [ ~ Swedish approach ]
Simulation data graphed above illustrate crucial dependence of infection peak and
overall spread in the population on the fraction of identified infectious individuals (IID).
For testing procedures with IID < 25%, curves deviate only weakly from uncontrolled outbreak.
Similarly, results for more than 10 days between tests
or delays of more than 5 days between testing and isolation of identified cases
also approximate uncontrolled outbreaks.
https://www.medrxiv.org/content/10.1101/2020.10.21.20217331v1.full.pdf
Fauci: "Well, if people are not wearing masks, then maybe we should be mandating it"
As cooler weather comes, people need to "double down" on measures that work,
Fauci said. "Universal mask wearing" is one, he said,
as is keeping a distance from others and frequent hand washing.
"They sound very simple. But we're not uniformly doing that
and that's one of the reasons we're seeing these surges"
https://www.cnn.com/2020/10/23/health/fauci-covid-mask-mandate-bn/index.html
AstraZeneca, Johnson & Johnson resuming U.S. COVID-19 vaccine trials
Testing of AstraZeneca's vaccine candidate had been halted since early September,
while Johnson & Johnson's vaccine study was paused at the beginning of last week.
Each company had a study volunteer develop a serious health issue, requiring a review of safety data
Computer analyses of gene expression signatures identified 16 current drug compounds
as potential COVID-19 therapeutic candidates.
11 have confirmed efficacy against SARS-CoV-2,
including clofazimine, ciclosporin, ciclopirox, and metixene.
https://www.biorxiv.org/content/10.1101/2020.10.23.352666v1.full.pdf+html
Heart damage does not seem to correlate with COVID-19 severity
COVID-19 is exceptional among 7 known human coronaviruses
for its ACE2 affinity and extensive cardiac involvement,
and the heart is one of many organs with high expression of ACE2.
SARS-CoV-2 has marked tropism for the heart and can lead to myocarditis (inflammation of the heart),
necrosis of its cells, mimicking of a heart attack, arrhythmias,
and acute or protracted heart failure (muscle dysfunction). These complications,
which at times are the only features of coronavirus disease 2019 (COVID-19) clinical presentation,
have occurred even in cases with mild symptoms and in people who did not experience any symptoms.
https://science.sciencemag.org/content/370/6515/408
Independent analysis finds AstraZeneca's AZD1222 COVID-19 vaccine candidate works
[ not yet peer-reviewed ]
"This is an important study as we are able to confirm that the genetic instructions
underpinning this vaccine, which is being developed as fast as safely possible,
are correctly followed when they get into a human cell."
https://www.bristol.ac.uk/news/2020/october/oxford-covid-19-vaccine-.html
On 15 October, WHO released Solidarity's preliminary results
for drugs that had raised earlier hopes - and they're a disappointment.
"The take-home from this is that the cavalry is not coming,"
says Ilan Schwartz, an infectious disease researcher at the University of Alberta, Edmonton.
https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
Vermont continues managing COVID-19 well, with no related deaths in more than 2 months.
Unlike many other Republican politicians around the country,
Phil Scott has consistently told residents to take the virus seriously.
"He started wearing a mask early in the pandemic
and has stood at the back of the room in many of the state's coronavirus briefings,
letting Dr. Mark Levine, Vermont's answer to Dr. Anthony Fauci, dominate proceedings,"
Vermont has two strong local media organizations - VTDigger and Seven Days -
that keep residents informed and that both took an intriguing step early in the pandemic:
They shut down their comments sections, to prevent misinformation from spreading.
In a randomized, controlled trial of 243 people with moderate COVID-19,
tocilizumab significantly reduced neither deaths nor need for ventilation.
https://www.nejm.org/doi/10.1056/NEJMoa2028836
Data from 1083 counties (34% of U.S. counties, 82% of U.S. population) in 49 states show
a 7% drop in COVID-19 hospitalizations up to 12 weeks following county mask mandates,
after controlling for age categories by county, testing access, case counts
and population mobility.
https://www.medrxiv.org/content/10.1101/2020.10.21.20208728v1
Moderna completes enrollment of 30,000 vaccine trial participants
Phase 3 COVE study of mRNA-1273 is being conducted in collaboration with
National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH
and the Biomedical Advanced Research and Development Authority (BARDA),
part of the Office of the Assistant Secretary for Preparedness and Response
at the U.S. Department of Health and Human Services.
To date, more than 25,650 participants have received their second vaccination.
20% are Latino and 10% are Black.
The study includes more than 7,000 Americans over the age of 65
and more than 5,000 Americans who are under the age of 65
but have high-risk chronic diseases that put them at increased risk of severe COVID-19,
such as diabetes, severe obesity and cardiac disease.
These medically high-risk groups represent 42% of the total.
Moderna is one of four U.S. Phase 3 trials of coronavirus vaccines,
each involving tens of thousands of participants.
Moderna started its Phase 3 trial July 27, and Pfizer started its trial that evening.
AstraZeneca started its U.S. trial August 31
and paused it about a week later when a participant fell ill.
Johnson & Johnson started its trial September 23
and paused it less than three weeks later for the same reason.
Both of those pauses are still in effect.
https://www.cnn.com/2020/10/22/health/moderna-covid-19-vaccine-trial-30000-participants/index.html
https://www.cnn.com/2020/10/22/health/moderna-covid-19-vaccine-trial-30000-participants/index.html
Roche is collaborating with Atea Pharmaceuticals to develop AT-527,
an orally administered drug to treat COVID-19 patients not yet hospitalised.
"In jointly developing and manufacturing AT-527 at scale, we seek to make
this treatment option available to as many people around the world as we possibly can."
Long-Term Care Policy after COVID-19 - Solving the Nursing Home Crisis
Since the U.S. outbreak began in a nursing home in Kirkland, Washington, more than
153,000 residents and employees of 7700 U.S. nursing homes have contracted COVID-19,
accounting for 35% of the country's deaths
(1) substantially increased Medicaid funding in care in all settings, including home-based;
(2) better, safe, affordable residential options;
(3) a more coherent financing system to pay for long-term care.
https://www.nejm.org/doi/10.1056/NEJMp2014811
NY COVID-19 hospital death rate dropped from 27% in March to 3% in August
Younger, healthier group of people were getting infected and were arriving at the hospital
with less-severe symptoms than those infected in the spring. Treatment also improved.
https://medicalxpress.com/news/2020-10-declines-death-covid-.html
FDA entertains debate about COVID-19 vaccine trial end games
If a vaccine receives an EUA before final testing is finished,
will that destroy chances of ever learning just how well that shot
- and maybe competitors still being studied - really work?
https://medicalxpress.com/news/2020-10-experts-thorny-vaccine-issues.html
The FDA's Vaccines and Related Biological Products Advisory Committee, convened to
go over the early results of COVID-19 vaccine clinical trials, declined to vote on any.
"Of note, the committee is not asked today to vote on any issues discussed"
https://www.vox.com/2020/9/30/21495092/fda-vaccine-covid-19-election-trump
COVID-19's wintry mix: As we move indoors, dry air will help the coronavirus spread
[ as regular readers should have noticed,
other reports suggest higher humidity is more problematic for COVID-19.
Extrapolating from flu and most colds (which are NOT from coronaviruses) is problematic.]
https://www.statnews.com/2020/10/21/covid19-winter-dry-indoor-air-helps-coronavirus-spread/
Analytical evaluation and critical appraisal of early commercial SARS-CoV-2 immunoassays
for routine use in a diagnostic laboratory: picking winners.
ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%.
Roche and the Euroimmun NC and S1 assays had best sensitivities overall; combining assays
detecting Euroimmun nucleocapsid and spike (S1/S2) antibody increased diagnostic yield.
https://www.medrxiv.org/content/10.1101/2020.10.20.20215970v1
Could nutrition modulate COVID-19 susceptibility and severity of disease? A systematic review
"to date, there is limited evidence that high-dose supplements of micronutrients
will either prevent severe disease or speed up recovery...there is no conclusive evidence
supporting adoption of novel nutritional therapies...prevention of obesity,
and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes"
https://www.medrxiv.org/content/10.1101/2020.10.19.20214395v1
Analytical solution of equivalent SEIR and agent-based model of COVID-19;
showing the bounds of contact tracing
"We identify the most sensitive parameters as undocumented transmission rate and documentation ratio.
Unfortunately, these are the parameters we have the least knowledge.
...even in the case of high contact tracing,
we cannot bring the outbreak to stalemate without applying substantial quarantine"
"the seemingly same parameters of the SEIR models and agent-based models
are not equivalent"
https://www.medrxiv.org/content/10.1101/2020.10.20.20212522v1.full.pdf+html
Low-Cost Manually Assembled Open Source Reader for Isothermal Pathogen Detection
from Saliva using RT-LAMP: SARS-CoV-2 Use Case
A complete guide to the construction of the reader
as well as the production of the reaction chemistry are provided here.
https://www.medrxiv.org/content/10.1101/2020.10.19.20215319v1.full.pdf+html
Voting in person is relatively safe even amid the COVID-19 pandemic,
roughly as risky as going to the grocery store.
Elections have been held during the COVID-19 pandemic
and there isn't much evidence that they've led to major new clusters of cases.
There were a few dozen confirmed cases linked to people who voted in Wisconsin
or worked at a voting location.
Stanford Medicine launches home COVID-19 testing study covering greater San Francisco
Self-collection testing kits and online reporting to estimate rate among 8.5 million residents.
https://catchstudy.stanford.edu/
Aridis Pharmaceuticals AR-711 inhaled neutralizing antibody successfully cleared
signs of SARS-CoV-2 from infected hamsters at a far lower dose in 4 days.
compared with other experimental monoclonal antibodies. Human trials are planned for 1H21.
https://www.biorxiv.org/content/10.1101/2020.10.14.339150v1
White House pandemic response crippled by infighting, lethargy and Trump
Doctors on the White House coronavirus task force have been sidelined by Scott Atlas,
whom colleagues said they regard as ill-informed, manipulative and at times dishonest.
He's a neuroradiologist with no background in infectious diseases,
who has won Trump's favor while asserting that the pandemic is nearly over,
that social distancing and masks don't work, and that
vulnerable people should be sequestered in nursing homes
while the coronavirus is allowed to spread naturally through the rest of the population.
Birx, whose profile and influence has eroded considerably since Atlas's arrival,
told Pence's office that she does not trust Atlas, does not believe he is giving Trump sound advice
and wants him removed from the task force, the two people said.
On Saturday, Atlas wrote on Twitter that masks do not work, prompting the social media site
to remove the tweet for violating its safety rules for spreading misinformation.
CVS Health said Monday that it wants to immediately hire 15,000 employees
to prepare for an expected rise in COVID-19 and flu cases this fall
More than 10,000 of those will be full-time and part-time licensed pharmacy technicians
who can help dispense medications and administer COVID-19 tests.
Since March, CVS has hired about 76,000 full-time, part-time and temporary employees.
It has about 300,000 employees and expects to administer 18 million flu shots this year
- up from 11 million last year.
States "finalize" their COVID-19 vaccine distribution plans
The plans were as detailed as they could be given the many things that are still unknown, e.g.:
When a vaccine or vaccines will become available.
Which groups will be first in line to get it and who comes next.
What kind of storage and refrigerator or freezer requirements they might have.
At least one candidate must be stored at -94 degrees.
For vaccines that require two doses (all but one), when the second dose must be administered.
Information about whether a certain vaccine works or doesn't work in specific populations
such as the elderly, pregnant women or the young.
The first phase is likely to be front-line health care workers.
[ will those already with antibodies be vaccinated? ]
That will make it relatively easy because most vaccinations will take place at hospitals.
It's when things get to the phase which includes people at greater risk
for becoming seriously ill or dying of COVID that it gets more complicated.
WARPED distribution plan
[ if vaccines are already manufactured, why wait until after EUA to distribute? ]
COVID-19 cough cloud propagation, masked vs unmasked
cloud volume without a mask is about 7 times larger than with a surgical mask
and 23 times larger than with an N95 mask.
It's the first 5 to 8 seconds after coughing that matter for suspending the exhaled droplets
in the air and, consequently, for the spread of the disease. After that time,
the cough cloud typically starts to disperse.
https://phys.org/news/2020-10-covid-clouds-presence-absence-masks.html
COVID-19 vaccine questions with answers by Andrea Amalfitano,
dean of the MSU College of Osteopathic Medicine and Osteopathic Heritage Foundation
Endowed Professor of Pediatrics, Microbiology and Molecular Genetics.
"we have no track record of successfully developing a coronavirus-specific vaccine,
let alone a COVID-19-specific vaccine"
https://medicalxpress.com/news/2020-10-qa-covid-vaccine.html
COVID-19 treatment options [ nothing recommended here if not needing extra oxygen ]
steroids such as dexamethasone can lower the risk of dying for severely ill patients,
but they may do the opposite for those who are only mildly ill.
https://medicalxpress.com/news/2020-10-treatment-options-covid-.html
Ohio State University have developed a new lab testing procedure
for detecting antibodies against SARS-CoV-2 that gives results
more quickly than existing assays and specifically identifies
so-called "neutralizing" antibodies - those that protect by blocking infection of cells.
"With many assays currently in use, we can detect antibodies,
but that doesn't tell us if they're neutralizing antibodies."
Over 14% of those who had been hospitalized had no or very low levels of antibodies,
and less than half had antibody concentrations high enough for plasma donation.
https://medicalxpress.com/news/2020-10-lab-potential-effects-covid-antibodies.html
Eliminating SARS-CoV-2 across much of the world, while perhaps not impossible,
could take a significant number of years. AstraZeneca has deals in place
to produce 2 billion vaccine doses by the end of 2021;
do the math for 2 doses and the world's 7 billion population.
https://theconversation.com/is-reaching-zero-covid-19-possible-145108
Structural analysis of full-length SARS-CoV-2 spike protein from Novavax vaccine candidate
Overall, NVAX-CoV2372 was found to be stable, homogeneous,
and locked in the antigenically preferred prefusion conformation.
With structural, biophysical, and antigenic characterization now complete,
ongoing evaluation in humans will provide the true proof-of-principle for this vaccine concept.
https://science.sciencemag.org/content/early/2020/10/19/science.abe1502
In a forward stepwise procedure in a multivariable model for case rate,
percentages of the state population that were Hispanic or black, median age,
median income, population density, and (residual) percentage poverty
explained 62% of the variation between states in case rates.
Adjusting for these factors, states with Democrats as the party in power
have lower case rates than Republican-led states.
https://www.medrxiv.org/content/10.1101/2020.10.16.20213892v1
Quantifying Asymptomatic Infection and Transmission of COVID-19 in New York City
using Observed Cases, Serology and Testing Capacity
the proportion of symptomatic cases is low, ranging from 13% to 18%,
If asymptomatic infections transmit at similar rates than symptomatic ones,
reproductive number estimates range from 3.2 to 4.4.
https://www.medrxiv.org/content/10.1101/2020.10.16.20214049v1
Video:
Industry leaders discuss how real-world COVID-19 data are already being applied,
and their potential shortcomings as the race for effective vaccines or treatments continues.
They also discuss unlikely alliances that have formed across institutions to help share these data,
and how these collaborative efforts may have far-reaching impacts beyond the pandemic.
https://www.statnews.com/2020/10/20/stat-conversations-beyond-real-world-data-and-covid-19/
Certain oral antiseptics and mouthwashes may inactivate SARS-CoV-2
1% baby shampoo solution, often used by head and neck doctors to rinse sinuses,
inactivated greater than 99.9% of human coronavirus after a two-minute contact time.
Listerine Antiseptic was able to decreases the infectious virus levels
by greater than 4 log10, or greater than 99.99%.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26514
All U.S. testing sites are legally required to report their results, positive and negative,
to public health agencies. But state health officials say many rapid tests are going unreported,
which means some new COVID-19 infections may not be counted.
About half of the nation's daily testing capacity now consists of rapid tests.
https://medicalxpress.com/news/2020-10-millions-virus-rapid-results.html
Phase 3 COVID-19 vaccine trial comparisons
Moderna will conduct interim analyses at about 53 and 106 infections.
AstraZeneca is doing one at about 75 cases.
Pfizer is doing four at 32, 62, 92, and 120 cases.
If most of the infections are in the placebo group - say 26 out of 32 -
that would suggest the vaccine is at least 76% effective.
Close to 50% of trials fail in Phase 3.
Phase 1/2 review
Rational approach toward COVID-19 main protease inhibitors via molecular docking,
molecular dynamics simulation and free energy calculation
saquinavir, aclarubicin, TMC-310911, and faldaprevir are potential inhibitors.
https://www.nature.com/articles/s41598-020-74468-0
7 tips as COVID-19 cases rise and colder weather heightens risk [ nothing new ]
Avoid crowds and keep some distance
Wear a face mask
Avoid touching your eyes, nose and mouth
Wash your hands
Keep surfaces clean
Take care of your mental health
Recognize the symptoms
LabCorp launched Cov2Quant IgG COVID-19 antibody test designed to gauge
the strength of a person's immune response to the virus, for use in clinical trials.
LabCorp has performed more than 17 million molecular tests
since first making the COVID-19 test available in March
and is now able to process 210,000 tests per day, with plans to increase capacity further.
The company also has performed 3 million COVID-19 antibody tests
with the capacity to perform 300,000 per day.
only Missouri and Vermont reported better than 10% decrease in weekly cases
Cases in Connecticut and Florida, on the other hand, increased by 50% or more.
10 to 50% increases were reported in 27 states,
including Arizona, Colorado, Georgia, South Carolina, Texas and Washington
https://www.cnn.com/2020/10/18/health/us-coronavirus-sunday/index.html
Drive-throughs are busier than ever during the pandemic
- but they're hotspots for air pollution
Drive-through employees are regularly exposed to toxic fumes that can have
long-term health effects. Customers in their cars weren't much safer either.
Rather than being protected from emissions inside a vehicle,
studies show that pollutants can accumulate within your car while you're inside,
often to higher levels in the confined space than outside it.
Saturday, Germany reported 7830 new COVID-19 cases, a daily record
On Friday, the Czech Republic reported 11,105 new daily cases of COVID-19.
It was the first time the country recorded more than 10,000 cases in a day.
Campania, the Italian region that includes Naples,
has reported a daily infection rate five times higher than March's peak.
Three-month outcomes in hospitalized COVID-19 patients
71% of the patients still experienced neurological symptoms at 3 months
and the most common symptoms being fatigue (42%) and PTSD (29%).
64% of the patients report pain symptoms we well. Cognitive symptoms were found in 12%.
https://www.medrxiv.org/content/10.1101/2020.10.16.20211029v1.full.pdf+html
Medium-term effects of SARS-CoV-2 infection on multiple vital organs,
exercise capacity, cognition, quality of life and mental health, post-hospital discharge
At 2-3 months, 64% of patients experienced persistent breathlessness
and 55% complained of significant fatigue. On MRI, tissue signal abnormalities were seen
in the lungs (60%), heart (26%), liver (10%) and kidneys (29%) of patients
https://www.medrxiv.org/content/10.1101/2020.10.15.20205054v1
Aging and COVID-19 mortality: A demographic perspective
Using U.S. vital Statistics, COVID-19 mortality doubling time
is compared with 68 major cause of death categories.
First, COVID-19 mortality increasing exponentially with age at a rate near
the median of aging-related causes of death, as well as pneumonia and influenza.
Second, COVID-19 mortality levels in the U.S. are currently 4 to 8 times higher
than pneumonia and influenza across the adult age range.
Third, the relationship between COVID-19 fatality and age
varies considerably across high-income countries.
https://www.medrxiv.org/content/10.1101/2020.10.15.20213454v1.full.pdf+html
Fauci's "grand rounds" session at Thomas Jefferson University
He spoke for 30 minutes at noon in his familiar Brooklyn-accented rasp, via Zoom,
then took questions from a panel of Jefferson faculty and students.
John Zurlo, Jefferson's chief of infectious diseases, asked Fauci
why he projects that the vaccines might be 70% effective,
rather than the higher levels of protection afforded by many other inoculations.
Zurlo also asked Fauci to pick a favorite among the various kinds of vaccines now in development.
That drew a laugh from Fauci, "I don't even know.
It would be foolish to predict what is going to be better."
"We shouldn't be lulled into complacency that this is only an old-person disease," he said.
"If you look at the general population,
about 40% of individuals have susceptibility to severe COVID disease."
Fauci said that if the vaccine is 70% effective, and if some people resist taking it,
many months will elapse before society reaches herd immunity.
"You're not going to have a profound degree of herd immunity for a considerable period of time,
maybe toward the end of 2021, into 2022"
"It's not going to be the way it was with polio and measles, where you get a vaccine,
case closed, it's done. It's going to be public-health measures that linger for months and months."
https://www.inquirer.com/health/coronavirus/covid19-fauci-vaccine-november-jefferson-masks-social-distance-20201015.html
BioNTech and Pfizer BNT162b1 and BNT162b2 phase 1 trial review
Systemic events in response to BNT162b2 were milder than those in response to BNT162b1;
serologic and immune responses elicited by BNT162b1 and BNT162b2 were similar;
BNT162b2 was advanced to a phase 2-3 safety and efficacy evaluation
https://www.nejm.org/doi/full/10.1056/NEJMoa2027906
Coronavirus treatments: some progress, no panacea
Dexamethasone is the only treatment proven to reduce coronavirus mortality
and has shown promise in early trials among hospitalised patients requiring oxygen.
It has been endorsed as a COVID-19 treatment
by both the World Health Organization (WHO) and the European Medicines Agency.
Antibody treatments by intravenous plasma from recovered patients showed early promise;
artificial antibody treatments are still experimental.
https://medicalxpress.com/news/2020-10-coronavirus-treatments-panacea.html
[ more on SARS-CoV-2-PLpro ]
Information gleaned by the American team helped Polish chemists to develop 2 molecules
that inhibit an enzyme called SARS-CoV-2-PLpro, which processes
ubiquitin and ISG15 much differently than its SARS-1 counterpart.
It promotes infection by sensing and processing both viral and human proteins.
"It stimulates the release of proteins that are essential for the virus to replicate,
and it also inhibits molecules called cytokines and chemokines
that signal the immune system to attack the infection"
The two inhibitor molecules, VIR250 and VIR251, very efficiently block SARS-CoV-2-PLpro activity,
but do not cross-react with human enzymes having similar function.
https://medicalxpress.com/news/2020-10-viral-molecular-scissor-covid-drug.html
Preclinical data suggest clinical evaluations of TMPRSS2 inhibitors,
androgen-deprivation therapy and androgen receptor antagonists
alone or in combination with anti-viral drugs
as early as clinically possible to prevent inflammation driven COVID-19 progression.
https://www.biorxiv.org/content/10.1101/2020.10.16.342782v1.full.pdf+html
The Theory and Practice of the viral dose in neutralization assay:
insights on SARS-CoV-2 "doublethink" effect.
Lowering standard dosage can potentially have a positive impact on
the detection and estimation of neutralizing antibodies present in a given sample,
showing higher sensitivity but similar specificity.
https://www.biorxiv.org/content/10.1101/2020.10.16.342428v1
Treos Bio's PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides
derived from all four major structural proteins of the SARS-CoV-2
that addresses the dual challenges of its potential heterogeneity
and individuals' immune response heterogeneities. [39 pages]
https://www.biorxiv.org/content/10.1101/2020.10.16.339937v1.full.pdf+html
PolyPEPI-SCoV-2 has been developed by Treos Bio Limited using its proprietary,
computational vaccine design technology. The company has transferred all rights,
including pending patent applications, for the preventive COVID-19 peptide vaccine
to a newly-formed subsidiary, PepTC Vaccines Limited (London, UK).
"we think we found a drug that is on par with remdesivir and is much cheaper"
an older antimalarial drug called amodiaquine was effective in eradicating SARS-CoV-2
in test tube experiments. Two other drugs, an anti-psychotic called zuclophentixol
and a blood pressure medication called nebivolol, also cleared the virus.
https://pubs.acs.org/doi/10.1021/acsptsci.0c00131
Act now, wait for perfect evidence later, says 'high priestess' of U.K. COVID-19 masking campaign
Trhisha Greenhalgh is a firm believer in evidence-based medicine, but COVID-19, she argues,
has revealed the limits of evidence-based medicine - masks being a potent case in point.
https://masks4all.co/
It was June before she and others prevailed on the WHO,
along with the U.S. Centers for Disease Control and Prevention and Public Health England,
to shift from claiming masks are potentially harmful to endorsing them.
https://www.sciencemag.org/news/2020/10/act-now-wait-perfect-evidence-later-says-high-priestess-uk-covid-19-masking-campaign
Airborne transmission of SARS-CoV-2
"one is far more likely to inhale aerosols than be sprayed by a droplet,
and so the balance of attention must be shifted to protecting against airborne transmission. "
https://science.sciencemag.org/content/370/6514/303.2
Pfizer Says It Won't Seek Vaccine EUA Before Mid-November
Friday's announcement represents a shift in tone for the company and its leader, who
has repeatedly emphasized the month of October in interviews and public appearances.
https://www.nytimes.com/2020/10/16/health/covid-vaccine-pfizer.html
[ more on NIH monoclonal SARS-CoV-2 antibody drugs phase 2 trials ]
The National Institute of Allergy and Infectious Diseases (NIAID) launched ACTIV-5 Big Effect Trial,
a clinical study designed to determine whether certain approved therapies or investigational drugs
in late-stage clinical development show promise against COVID-19 and merit advancement into larger clinical trials.
The trial will test risankizumab, a monoclonal antibody developed by Boehringer Ingelheim (Ridgefield, Connecticut)
and AbbVie (North Chicago, Illinois), in conjunction with the antiviral drug remdesivir,
compared to a placebo plus remdesivir. [ but the WHO has already concluded that remdesivir is a bogus treatment ]
The ACTIV-5/BET trial will also test the investigational monoclonal antibody lenzilumab,
developed by Humanigen (Burlingame, California), with remdesivir, compared to placebo and remdesivir.
https://www.precisionvaccinations.com/us-nih-begins-identifying-promising-covid-19-treatments
NIH begins large adaptive Phase 3 clinical trial of immune modulators for COVID-19 treatment
ACTIV-1 Immune Modulators (IM) will assess whether infliximab (REMICADE), abatacept (ORENCIA),
and/or Cenicriviroc (CVC) modulate immune response, reduce the need for ventilators and shorten hospital stays.
https://medicalxpress.com/news/2020-10-nih-large-clinical-trial-immune.html
Quantifying the adhesive strength between the SARS-CoV-2 S-proteins
and human receptor and its effect in therapeutics
Using a mechanistic model to analyze virus uptake,
S-proteins/ACE2 receptor's binding has to be reduced at least by 50%
to block the uptake of SARS-CoV-2 particles having radius between 30 to 70 nm. However,
the effectiveness of these strategies is strongly dependent on particle size and receptor density.
Hence, such treatments might be more effective in blocking only a portion of the SARS-CoV-2 particles
leaving others unaffected.
https://www.nature.com/articles/s41598-020-74189-4
Multi-organ impairment in low-risk individuals with long COVID
In a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment
in one or more organs 4 months after initial symptoms of SARS-CoV-2 infection.
https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1
How to remove the testing bias in CoV-2 statistics
The positive rate (the ratio of positive tests to the total number of tests)
is uninformative in the presence of non-representative testing.
Testing is important, but adding up confirmed infections from all sorts of tests is misleading.
A severity index for epidemics is proposed that is comparable over time.
This index is based on COVID-19 cases and can be obtained if reasons for testing are known.
[ well-written, but lots of equations; 13 pages ]
https://www.medrxiv.org/content/10.1101/2020.10.14.20212431v1.full.pdf
The effect of influenza vaccination on trained immunity: impact on COVID-19
A quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2,
which may result in relative protection against COVID-19, suggesting
deployment in the 2020-2021 influenza season to protect against both infections
https://www.medrxiv.org/content/10.1101/2020.10.14.20212498v1
pandemic debacles: CDC vs Birx
Birx replaced a functional, if imperfect, CDC data system
- well understood by hospitals and state health departments -
with an error-ridden and unreliable filter on hospital needs
that sometimes displays nonsensical data, such as negative numbers of beds.
The Department of Health and Human Services (HHS) data hub for hospital capacity,
including inpatient beds occupied overall and by COVID-19 patients,
now draws on data collected by TeleTracking, a for-profit company with nearly 400 employees,
whose majority owner, real estate developer Michael Zamagias, has donated to Republican candidates
and has ties to Trump businesses through colleagues, according to an NPR report.
https://www.sciencemag.org/news/2020/10/inside-story-how-trumps-covid-19-coordinator-undermined-cdc
U.S. COVID-19 cases increasing for a third time
Heading into the fall and winter, there are clear signs of a third resurgence
bearing a close resemblance to what was seen in early June.
[ check out "Daily Cases By Region" ]
https://time.com/5893916/covid-19-coronavirus-third-wave/
Those looking for good news at the outset of the third wave do have something to point to:
the lethality of the disease. Thanks to some combination of the age distribution of cases,
improved treatments and better understanding of the disease,
more vigilance in protecting the country's most vulnerable,
and more widespread mask-wearing,
which can reduce the viral load of any exposure and thereby perhaps the risk of infection,
the COVID-19 fatality rate appears much lower than it was in the spring.
While the real fatality rate is a matter of some dispute and contestation,
in August,
Youyang Gu, then the pandemic's most accurate modeler,
calculated that it had fallen to 30% of its first-wave peak.
https://nymag.com/intelligencer/2020/10/the-third-wave-of-covid-19-is-here.html
Vaccination of nonhuman primates with Moderna's mRNA-1273
induced robust SARS-CoV-2 neutralizing activity,
rapid protection in the upper and lower airways,
and no pathologic changes in the lung.
https://www.nejm.org/doi/full/10.1056/NEJMoa2024671
Genetic Risk of Severe COVID-19 associations at multigene locus 3p21.31
and ABO blood group locus 9q34.2
The strongest signal was the rs11385942 insertion-deletion GA or G variant at locus 3p21.31.
The markedly lower mortality with dexamethasone treatment added to usual care
among patients with COVID-19 who received mechanical ventilation provides strong evidence
that death may be caused by a late hyperinflammatory phase.
https://www.nejm.org/doi/full/10.1056/NEJMe2025501
model of SARS-CoV-2 spread in various temperatures and relative humidities
"We found that in most situations, respiratory droplets travel longer distances than
the 6-foot social distance recommended by the CDC"
This effect is increased in the cooler and more humid environments to distances of up to 6 meters (19.7 feet)
before falling to the ground in places such as walk-in refrigerators and coolers,
where temperatures are low and humidity is high to keep fresh meat and produce
from losing water in storage. In addition to its ability to travel farther,
the virus is particularly persistent in cooler temperatures, remaining
"infectious from several minutes to longer than a day in various environments"
https://pubs.acs.org/doi/10.1021/acs.nanolett.0c03331
Nanoluciferase is a small enzyme with the brightest bioluminescence reported to date.
SARS-CoV-2-Nluc was used to identify
nelfinavir, rupintrivir, and cobicistat as its most selective inhibitors.
https://www.nature.com/articles/s41467-020-19055-7
Multiple human genes correlated with COVID-19 severity
The U.K. genetics study did not confirm that ABO variants affect the odds of severe disease.
Some studies looking directly at blood type, not genetic markers, have reported that
type O blood protects against COVID-19, whereas A blood makes a person more vulnerable.
It may be that blood type influences whether a person gets infected, but not how sick they get,
says Stanford University geneticist Manuel Rivas.
In any case, O blood offers at best modest protection.
"There are a lot of people with O blood that have died of the disease. It doesn't really help you"
https://www.sciencemag.org/news/2020/10/found-genes-sway-course-coronavirus
Scientists are hoping to generate superior immune responses
with inhaled vaccines that directly target airway cells which the virus invades.
"The first generation of vaccines are probably going to protect a lot of people,
but I think it's the second- and third-generation vaccines
- and maybe intranasal vaccines will be a key component of this -
that ultimately are going to be necessary.
Otherwise, we'll continue to have community transmission."
https://medicalxpress.com/news/2020-10-inhaled-vaccines-aim-coronavirus.html
As previously noted, University of Texas has been working with niclosamide for this.
https://www.precisionvaccinations.com/inhalable-therapy-covid-19-needs-support
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept
Ivermectin is a widely used antiparasitic drug
with known efficacy against several single-strain RNA viruses.
https://www.nature.com/articles/s41598-020-74084-y
NIH launches monoclonal SARS-CoV-2 antibody drugs phase 2 trials,
testing approved monoclonal antibody risankizumab with remdesivir
and experimental monoclonal antibody lenzilumab with remdesivir.
Lenzilumab is currently being tested separately in a phase 3 COVID-19 study.
https://medicalxpress.com/news/2020-10-nih-trial-antibody-drugs-covid-.html
Considerations for diagnostic COVID-19 tests [ also readable, but less compelling; 10 pages ]
[ IMO, poor contact tracing and/or quarantining forfeits much of testing benefit ]
https://www.nature.com/articles/s41579-020-00461-z.pdf
An increase in the incidence of sudden smell and taste change in the general population
may be used as an indicator of COVID-19 spread in the population.
https://www.nature.com/articles/s41467-020-18963-y
How anti-ageing drugs could boost COVID vaccines in older people [ duh ]
One promising class of anti-ageing drug acts on pathways involved in cell growth.
These drugs inhibit a protein known as mTOR. In the laboratory,
inhibiting mTOR lengthens lifespan in animals from fruit flies to mice.
Elderly adults who received a low-dose mTOR inhibitor for 6 weeks had fewer infections
in the year after the study and an improved response to the flu vaccine,
but a phase 3 trial with a similar mTOR inhibitor called RTB101 failed.
https://www.nature.com/articles/d41586-020-02856-7
Gastrointestinal involvement attenuates COVID-19 severity and mortality
Unexpectedly, we observed that GI involvement was associated with a significant reduction
in disease severity and mortality, with an accompanying reduction in key inflammatory proteins
including IL-6, CXCL8, IL-17A and CCL28 in circulation.
https://www.medrxiv.org/content/10.1101/2020.09.07.20187666v1
Roche will launch Elecsys SARS-CoV-2 Antigen test, a high-volume automated lab assay.
It can process up to 300 per hour on a single machine,
while individual results are available in less than 20 minute,
and can be used either as a complement or an alternative to PCR-based molecular testing.
"Performance evaluations around sensitivity and specificity of the test are ongoing
and will be shared at the time of launch."
https://www.roche.com/media/releases/med-cor-2020-10-13.htm
Data from measurement of small droplet aerosol concentrations in public spaces
using handheld particle counters to estimate the relation between
aerosol persistence time and the risk of infection with SARS-CoV-2.
https://www.medrxiv.org/content/10.1101/2020.10.13.20211839v1
Virus detection and identification in minutes using single-particle imaging and deep learning
achieves labeling, imaging and virus identification in less than 5 minutes
and does not require analysis, purification or amplification steps.
https://www.medrxiv.org/content/10.1101/2020.10.13.20212035v1
Circulating Proteins Influencing COVID-19 Susceptibility and Severity: a Mendelian Randomization Study
Increased OAS1 levels was associated with reduced COVID-19 death, hospitalization and susceptibility.
OAS1 is an interferon-stimulated gene that promotes viral RNA degradation.
Other potentially implicated proteins included IL10RB. Available medicines,
such as interferon-beta-1b, increase OAS1 and could be explored for their effect on COVID-19.
https://www.medrxiv.org/content/10.1101/2020.10.13.20212092v1
Systematic analysis of electronic health records identifies drugs reducing risk of COVID-19 hospitalization and severity.
Several drugs and products sold in pharmacies are significantly associated with reduced odds of SARS-CoV-2 hospitalization and disease severity:
notably ubiquinone, ezetimibe, rosuvastatin, and flecainide.
Additionally, acquisition of surgical masks, latex gloves and several ophthalmological products,
including eye wipes were associated with decreased risk for hospitalization.
Ubiquinone, ezetimibe and rosuvastatin, all related to the cholesterol synthesis pathway,
are associated with a protective effect against COVID-19 complications.
https://www.medrxiv.org/content/10.1101/2020.10.13.20211953v1
COVID-19 mask effectiveness in Hilton Head, SC
Colder weather now arriving increases potential for virus outbreaks to spread.
More person-to-person contact will be inevitable with more indoor activities
and in-person classes in schools and colleges.
https://medicalxpress.com/news/2020-10-covid-cases-states.html
Clarifying predictions for COVID-19 from testing data: the example of New-York State
Their model addresses asymptomatic contagion and employed Bayesian methods
to correct some known biases. NYS deployed pseudo-random testing separately from
those for critical workers and patient diagnoses. In this paper, researcher tuned a model to
predict actual cases based on that pseudo-random testing and explored the diminishing
returns for increasing per capita testing rate by 10x and 100x.
https://www.medrxiv.org/content/10.1101/2020.10.10.20203034v1.full.pdf+html
Hydroxychloroquine does not counter SARS-CoV-2 in hamsters, high dose of favipiravir does
A low dose of the drug favipiravir did not have this outcome.
In the past, the drug has already been prescribed in high doses to Ebola patients,
who appear to have tolerated it well.
https://www.pnas.org/content/early/2020/10/08/2014441117
Researchers have created the first full dynamic map of how cells learn to fight microbes
and then preserve a memory of this for future infections.
"Further investigations are needed
to confirm that human cells have a similar map to mouse CD4+ T cells."
https://www.nature.com/articles/s41590-020-0800-8
China joins WHO's COVAX vaccine program, intended to promote fair distribution
As of Friday, more than 150 economies equalling nearly two-thirds of the world's population
have signed commitment agreements to the COVAX Facility in its effort to ensure
low- and middle-income countries have equitable access to a vaccine when one is developed.
The U.S., having requested to leave the WHO, has also declined to participate in this effort.
Age of an individual does not indicate likelihood of COVID-19 infection. However,
development of symptoms, progression of the disease, and mortality are age-dependent.
https://www.nature.com/articles/s41598-020-73777-8
ILC Therapeutics, a Scottish biotech company, has announced that
its unique synthetic Interferon called Alfacyte
is more effective at preventing the spread of SARS-CoV-2 in cell culture
than other commercially-available Interferons such as Interferon Alpha 2 and Interferon Beta 1a.
Alpha Interferons are a family of 12 natural proteins which everyone produces.
https://www.businesswire.com/news/home/20201007005920/en/
AstraZeneca begins phase 3 U.K. trial of AZD7442 COVID-19 vaccine candidate.
[ Not to be confused with their AZD1442, which U.S. trial remains on hold. ]
AZD7442 is a combination of two long-acting antibodies
derived from convalescent patients after SARS-CoV-2 infection.
It was discovered by Vanderbilt University Medical Center
and licensed to AstraZeneca in June 2020. The company said it has received
around $486 million from the U.S. for the development and supply of AZD7442.
Identifying Optimal COVID-19 Testing Strategies for Schools and Businesses:
Balancing Testing Frequency, Individual Test Technology, and Cost
Testing every 3 days versus every 14 days (even with a lower sensitivity test)
reduces the disease burden substantially. Pooling provided cost savings
and made a high-frequency approach practical; one high-performing strategy, testing every 3 days,
yielded per person per day costs as low as $1.32.
https://www.medrxiv.org/content/10.1101/2020.10.11.20211011v2
Machine learning based prognostic model and mobile application software platform
for predicting infection susceptibility of COVID-19 using health care data:
clinicians and government officials can focus on the highly susceptible people for limiting pandemic spread
https://www.medrxiv.org/content/10.1101/2020.10.09.20165431v1
The AncestryDNA COVID-19 Study collected self-reported survey data
on symptoms, outcomes, risk factors, and exposures
for over 563,000 adult individuals in the U.S., including over 4,700 COVID-19 cases
as measured by a self-reported positive nasal swab test,
and observed significant associations between several risk factors
and COVID-19 susceptibility and severity outcomes.
https://www.medrxiv.org/content/10.1101/2020.10.08.20209593v1
A Sampling-Testing-Quarantine (STQ), strategy for identifying
and isolating individuals with asymptomatic SARS-CoV-2 in order to mitigate the epidemic
Studies suggest that as much as 79% of spread is through asymptomatic carriers
and there could be anywhere from 3-40 times as many asymptomatic cases as symptomatic.
Random selection from the general population for testing (regardless of symptoms),
can identify enough asymptomatic but infectious cases to reduce and delay the epidemic.
Further, this sampling helps to identify household members of infectious cases
who are also more likely than others to be infected. [ That is basically what New York did ]
https://www.medrxiv.org/content/10.1101/2020.10.07.20208686v1.full.pdf+html
Australia's national science agency CSIRO suggest SARS-Cov-2 can survive 28 days
in dark rooms at 68F on smooth, no-porous surfaces.
https://www.bbc.com/news/health-54500673
Wu Guizhen, the chief bio-safety expert at China's Disease Control and Prevention Center,
told state broadcaster CCTV last month that the country's coronavirus vaccine
could be ready for general public use as early as November.
"I believe it's very likely they'll be the first to announce the successful development of a vaccine,"
said Yanzhong Huang, a senior fellow for global health at the Washington-based Council on Foreign Relations.
"But the key question is how well the international society,
especially the scientific community, will recognize it."
https://www.cnn.com/2020/10/09/asia/china-covid-vaccine-global-race-intl-hnk/index.html
Remdesivir for treating COVID-19 - Final Report: better than nothing
In 1062 patients in a double-blind, randomized, placebo-controlled trial
(with 541 assigned to remdesivir and 521 to placebo),
those who received remdesivir had a median recovery time
of 10 days (95% confidence interval [CI], 9 to 11),
as compared with 15 days (95% CI, 13 to 18) among those who received placebo.
https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
Daily washing of cloth masks reduces likelihood of virus contamination and transmission
2015 study is the only randomized controlled trial of cloth mask antiviral efficacy.
https://bmjopen.bmj.com/content/10/9/e042045
Azvudine (FNC): another clinical candidate for COVID-19 treatment
2'-deoxy-2'-B-fluoro-4'-azidocytidine (Azvudine, FNC),
a clinical candidate originally developed for HIV treatment,
has entered clinical trial in China for evaluating its COVID-19 treatment efficacy and safety
https://www.nature.com/articles/s41392-020-00351-z
Dense cities should brace for long coronavirus outbreaks, contrasted with
relatively short, intense spikes in COVID-19 cases in relatively uncrowded cities
where residents stick to their own neighbourhoods rather than mingling freely.
https://www.nature.com/articles/d41586-020-00502-w
Direct detection of SARS-CoV-2 using CRISPR-Cas13a and a mobile phone
The assay accurately detected a set of positive clinical samples in under 5 minutes,
combining crRNAs targeting SARS-CoV-2 RNA to improve sensitivity and specificity.
Unlike previous CRISPR diagnostics, it does not require pre-amplification of the viral genome.
By directly detecting viral RNA without additional manipulations,
the test yields quantitative RNA measurements rather than simply a positive or negative result.
Combined with mobile phone-based quantification,
this assay can provide rapid, low-cost, point-of-care screening.
https://www.medrxiv.org/content/10.1101/2020.09.28.20201947v1">
How SARS-CoV-2 disables the human cellular alarm system
Patients with severe COVID-19 symptoms also show low levels of interferon response,
suggesting that the interferon response is crucial for combatting the virus.
SARS-CoV-2 proteins attack three critical cellular processes to disrupt human protein production.
Some of the virus's proteins prevent mRNA from being fully spliced and properly assembled.
Others plug up the ribosome so that it cannot form new proteins.
Still other SARS-CoV-2 proteins interfere with the signal recognition particle and block protein transport.
https://phys.org/news/2020-10-sars-cov-disables-human-cellular-alarm.html">
FDA EUA for Abbott BinaxNOW $5 COVID-19 rapid antigen test
only covered testing for people within the first 7 days of developing symptoms, when viral loads remain high.
* too many false positive and false negative results from asymptotic testing.
"The point I'm trying to make here, and I'll be blunt, is that antigen testing will not
and cannot work for asymptomatic screening, and [it] will probably kill a lot of people"
https://www.theatlantic.com/health/archive/2020/10/do-rapid-antigen-tests-have-accuracy-problem/616681/>
Omixon has gained CE mark certification for its AzureSeq-200 CE in vitro diagnostic,
the COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test
to be cleared in Europe that does not require RNA extraction without closed systems,
Tests that require RNA extraction take significantly longer and require costly reagents
that can be hard to get during the pandemic. The automation-friendly test deliver results
in less than two hours and requires fewer steps, reducing chances of human error,
https://www.omixon.com/azureseq-200-ce-ivd/>
A high-throughput microfluidic nano-immunoassay for detecting anti-SARS-CoV-2 antibodies
in serum or ultra-low volume (pin prick) dried blood samples
Swiss method achieved a specificity of 100% and a sensitivity of 98%
based on the analysis of 289 human serum samples.
The nano-immunoassay analyzes 1024 samples in parallel
on a single microfluidic device the size of a USB stick.
https://www.medrxiv.org/content/10.1101/2020.10.07.20208280v1.full.pdf+html>
Findings from 1054 patients in the UK using the QIA-stat-Dx point-of-care testing platform,
which yield results in 1.7 hours suggest that testing suspected COVID-19 at the point-of-care
could help health-care providers better manage a surge in cases and reduce infection spread within the hospital,
compared with PCR testing in a centralised lab results in 21.3 hours.
https://medicalxpress.com/news/2020-10-rapid-bedside-faster-standard-centralised.html>
China's Fosun Pharmaceutical has received the FDA's approval for a U.S. clinical trial
of its investigational COVID-19 genetically engineered fully humanized monoclonal antibody treatment, HLX70.
Fosun subsidiary Hengenix Biotech will lead the early-stage study,
which will evaluate the monoclonal antibody's safety and pharmacokinetics in health volunteers.
https://www.henlius.com/en/NewsDetails-2780-26.html>
Wisconsin and the Dakotas now lead all other states in new cases per capita.
Mask usage is 39% in Wisconsin and 45% in the Dakotas, both below the U.S. average of 50%.
The Northeast is now seeing first signs of what might become a second wave of COVID-19.
https://medicalxpress.com/news/2020-10-upper-midwest-covid-surge-northeast.html>
Of 3,222 hospitalized COVID-19 patients aged 18-34,
21% required intensive care, 10% required mechanical ventilation and 2.7% died.
For comparison, the death rate of those in the same age group
hospitalized with heart attacks is approximately half of that figure.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2770542>
More on "live, attenuated" vaccines, such as BCG, to broadly increase immunity
This year, the flu vaccine comes in two major forms: a shot or a nasal spray.
The shot, which is approved for people all above age six months (who don't have contraindications),
contains an inactivated virus or components of the virus.
The nasal spray (FluMist), which is approved for people ages 2 to 49, contains live, attenuated flu viruses.
https://www.npr.org/sections/health-shots/2020/10/08/917831035/could-the-live-flu-vaccine-help-you-fight-off-covid-19
Only two U.S. states (Alabama and Hawaii) report a decline of new cases,
and nationwide hospitalizations are increasing.
Wisconsin, Utah, Montana, Nebraska, North Dakota, Oklahoma, South Dakota
and Wyoming have all seen record-high hospitalization numbers in the past days.
https://www.cnn.com/2020/10/08/health/us-coronavirus-thursday/index.html
Study suggests COVID-19 antibodies last at least 115 days after infection
The study is also the first to show these antibodies can also be detected in the saliva.
"The Lunenfeld-Tanenbaum Research Institute platform for detection of antibodies in serum,
or blood, is incredibly robust and well suited
for assessing the prevalence of infection within the community"
https://immunology.sciencemag.org/content/5/52/eabe5511
The editors of the New England Journal of Medicine
have broken with the medical journal's long tradition of avoiding political issues
and published a scathing criticism of the government's management of the COVID-19 crisis,
claiming that the FDA has been "shamefully politicized."
https://www.nejm.org/doi/full/10.1056/NEJMe2029812
Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing
SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) testing in one pot
is a streamlined assay that combines simplified extraction of viral RNA
with isothermal amplification and CRISPR-mediated detection.
This test can be performed at a single temperature in less than an hour
and with minimal equipment and sensitivity similar
to that of reverse-transcription-quantitative polymerase-chain-reaction (RT-qPCR) assays
https://www.nejm.org/doi/full/10.1056/NEJMc2026172
The Stress of Bayesian Medicine - Uncomfortable Uncertainty in the Face of COVID-19
The medical profession tends to select for individuals who crave a particular kind of mastery.
Though sometimes a single paper might break through and reach the front lines of medicine
in a matter of months, the truth is that these changes usually occur slowly,
allowing physicians to carefully update their knowledge and retain their claim on expertise.
COVID-19 has blown a hole in that version of medicine.
https://www.nejm.org/doi/full/10.1056/NEJMp2018857
Comparison of efficacy of Dexamethasone and Methylprednisolone in improving P/F
(partial pressure of arterial oxygen and fraction of inspired oxygen) ratio among COVID-19 patients
Both dexamethasone and methylprednisolone significantly improved the P/F ratio (p<0.05),
and dexamethasone was significantly more effective than methylprednisolone (p<0.05).
https://www.medrxiv.org/content/10.1101/2020.10.06.20171579v1
A Bayesian change point detection model using daily actively infectious cases
can be used to evaluate public health interventions,
identify latent events associated with spreading rates, and yield better short-term forecasts.
1) capture the epidemiological dynamics under the changing conditions
caused by external or internal factors;
2) provide uncertainty estimates of both the number and locations of change points;
3) adjust any explanatory time-varying covariates.
https://www.medrxiv.org/content/10.1101/2020.10.06.20208132v1
In a survey of 108 patients with mean age 55.5 (SD: 15.4) years,
27.8% were health-care workers, and 75.9% presented some type of symptoms.
Symptoms usually persist in COVID-19 patients 12 weeks after the acute episode,
especially in patients <65 and health-care workers. All had developed antibodies by 12 weeks.
https://www.medrxiv.org/content/10.1101/2020.10.06.20206060v1
Age- and Sex-Specific Modelling of the COVID-19 Epidemic
Under current mitigation measures as of mid-August,
active COVID-19 cases will double by the end of October 2020.
Infection rates will be highest among the young and working ages,
but will also rise among the old.
Sex ratios reveal higher infection risks among women than men at working ages;
the opposite holds true at old age.
Death rates in all age groups are twice as high among men as women.
https://www.medrxiv.org/content/10.1101/2020.10.06.20207951v1
Tocilizumab (TCZ), a humanized monoclonal anti-interleukin-6 receptor antibody,
may be beneficial in severely ill COVID-19 patients.
TCZ could have a detrimental impact on viral clearance if given prematurely.
https://www.nature.com/articles/s41598-020-74001-3
AstraZeneca's AZD1222 vaccine is already being reviewed for potential regulatory approvals
in Canada and Europe, but its U.S. trial is still paused while the FDA looks at data
from clinical studies of similar vaccines developed by the same scientists
that worked on AstraZeneca's COVID-19 vaccine.
https://www.fool.com/investing/2020/10/06/astrazenecas-coronavirus-vaccine-is-already-being/
A team of scientists in India has developed Feluda,
an inexpensive paper-based test for coronavirus
that could give results with 96% sensitivity and 98% specificity
in under an hour and cost about $6.75.
https://news.yahoo.com/indias-paper-covid-19-test-230147502.html
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
Combining mass spectrometry with UK's national synchrotron to probe
an essential enzyme of SARS-CoV-2 with over 1,250 unique small compound, termed fragments,
and identified 74 high-value fragment hits which can be used to develop new inhibitors
for this essential viral protein.
The team released all the experimental data as soon as it was generated;
an announcement on social media triggered a large international collaboration
that harnessed the combined knowledge of scientists worldwide
through a novel crowdsourcing initiative that they called COVID Moonshot.
https://www.nature.com/articles/s41467-020-18709-w
More discussion:
https://www.nature.com/articles/s41467-020-18710-3
Ranitidine bismuth citrate (RBC),
a commonly used drug with a safe and comprehensive pharmacological profile,
potently inhibits SARS-CoV-2 replication in human and animal cell lines
and in an established golden Syrian hamster model by disrupting the functions of helicase
and possibly other essential viral enzymes via an irreversible displacement of zinc(II) ions
from the enzyme by bismuth(III) ions.
https://www.nature.com/articles/s41564-020-00802-x
An N95 respirator blocked 99% of the cough aerosol, a procedure mask blocked 59%,
a 3-ply cloth face mask blocked 51%, and a polyester neck gaiter blocked 47%
as a single layer and 60% when folded into a double layer.
In contrast, the face shield blocked 2% of the cough aerosol.
https://www.medrxiv.org/content/10.1101/2020.10.05.20207241v1
Handling the COVID-19 crisis: Toward an agile model-based systems approach,
COVID-19 is not simply a health crisis. It is a global crisis that couples
the natural system, human society, the economic system and governance,
in ways we have not seen in over a century.
Only by viewing it and explicitly modeling it as a system of systems
can we manage the crisis in an optimal way and move society to a better place.
The worst case is a situation where a lockdown is ordered late,
only partially followed (with less than 80% compliance), and lifted too soon.
https://onlinelibrary.wiley.com/doi/full/10.1002/sys.21557
Suramin is a century-old medication used to treat African sleeping sickness and river blindness.
In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir,
the currently approved nucleotide drug for COVID-19.
https://www.biorxiv.org/content/10.1101/2020.10.06.328336v1
Monthly cases per 100,000 residents by state; cases by age group
In May, the median age of someone who tested positive for COVID-19 was 46 years old,
according to the CDC. In August, the median age for someone with a positive test was 38.
https://usafacts.org/articles/5-things-about-covid-19-september
Characteristics of SARS-CoV-2 and COVID-19
An extensive summary of clinical, epidemiological and pathological features of COVID-19,
recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection,
and the potential wildlife hosts and zoonotic origin of this emerging virus in detail.
https://www.nature.com/articles/s41579-020-00459-7
Inclusion of both S1 subunit of the spike glycoprotein and
nucleocapsid (N)-based ELISAs in serological testing
would capture as many potential SARS-CoV-2 positive cases as possible
and more than using any of them alone.
https://www.nature.com/articles/s41598-020-73491-5
Inhibition of SARS-CoV-2 papain-like protease (PLpro) not only inhibits viral replication,
but also rescues antiviral immunity, establishing PLpro as
a particularly promising target for further drug development.
https://www.nature.com/articles/s41392-020-00335-z
Phylogenetic analysis of 208 publicly available SARS-CoV-2 genome sequences
collected during the early outbreak phase was combined with Bayesian inference
under an epidemiological model to trace person-to-person transmission to show that
super-spreading events played an important role early in the COVID-19 outbreak.
https://www.nature.com/articles/s41467-020-18836-4
A transmission dynamic model, calibrated to U.S. state-level COVID-19 cases and deaths,
predicted as of 22 July that only three states were on track to curtail their epidemic curve.
https://www.nature.com/articles/s41562-020-00969-7
A validated, real-time prediction machine learning model
for favorable outcomes in hospitalized COVID-19 patients
Among 30 models previously reported, 8 underwent validation,
none predicted favorable outcomes and no studies reported clinical implementation.
https://www.nature.com/articles/s41746-020-00343-x
Hyaluronan is involved in the early stages of wound healing.
Since hyaluronan can bind large amounts of water in its web of long molecules,
it forms a jelly-like substance. This process runs riot in the alveoli of COVID-19 patients' lungs,
resulting in patients needing ventilator care and perhaps dying from respiratory failure.
https://medicalxpress.com/news/2020-10-liquid-gel-covid-patients-lungs.html
Recommended early isolation, social distancing, and increased quarantine period (at least 28 days)
after screening asymptomatic cases as well as their close contacts for chest CT scan
even after their negative nucleic acid testing to minimize the spread among the community.
https://www.medrxiv.org/content/10.1101/2020.10.06.20207597v1
This model suggests that herd immunity can be achieved at 34 to 48% of the population,
supposing those most liable to spread COVID-19 are vaccinated.
[ The authors unfortunately consider that strategy "will do the most good",
without considering who would be more likely to have serious consequences from infection. ]
https://www.medrxiv.org/content/10.1101/2020.10.05.20207100v1
State mandates are strongly correlated with higher rates of mask use,
and mandating use by all individuals in public spaces is more effective
than a less comprehensive mandate for mask use by all public facing employees.
https://www.medrxiv.org/content/10.1101/2020.10.03.20206326v1
Social distancing: natural experiment in 130 countries
After adjusting for multiple concurrent interventions and confounders,
and accounting for both timing and strictness of interventions,
* earlier and stricter school (-1.23 daily deaths per million, 95% CI -2.20 -0.27) and workplace
closures (-0.26, 95% CI -0.46 -0.05) were associated with lower COVID-19 mortality rates.
Only controlling for strictness international travel controls, and only controlling for timing
later restrictions on gatherings, were also associated with lower COVID-19 mortality.
Other interventions, such as stay-at-home orders or restrictions on public transport,
were not significantly associated with differences in mortality rates across countries.
Findings were robust across multiple statistical approaches.
Conclusions: Focusing on compulsory, particularly school closing,
not voluntary reduction of social interactions with mandated policies
appears to have been the most effective strategy to mitigate early COVID-19 mortality.
https://www.medrxiv.org/content/10.1101/2020.10.05.20206888v1
Review of repurposed drugs against COVID-19 including Tocilizumab, Remdesivir, Dexamethasome,
Lopinavir-ritonavir, Favipiravir, Hydroxychloroquine, and Convalescent plasma therapy.
Tocilizumab may reduce the mortality (<10%) of patients with COVID-19 with faster recovery time
and reduce the risk of patients with lung disease in falling into oxygen support.
https://www.medrxiv.org/content/10.1101/2020.10.04.20206516v1
Red cell agglutination tests have a long history in blood typing.
They do not require special equipment, are read by eye, have short development times,
low cost and can be applied as a Point of Care Test (POCT).
This paper describes a red cell agglutination test for the detection of antibodies
to the SARS-CoV-2 receptor binding domain (RBD) with a sensitivity of 90%
and specificity of 99% for detection of antibodies after a PCR diagnosed infection.
https://www.medrxiv.org/content/10.1101/2020.10.02.20205831v1
COVID-19 Viral Loads, Environment, Ventilation, Masks, Exposure Time, And Severity:
A Pragmatic Guide Of Estimates
Comparing a 3375 cubic foot office with 6 air exchanges per hour (per ASHRAE Standard 62.1)
with an comparable sized open space outdoor setting with a 3 MPH breeze
(1056 air exchanges per hour) shows that a similarly sized outdoor space has 176 times more
air exchanges over any given time period than a small office or a hospital room similar to
the reference cases used in this study. People wearing masks doing light work in a typical
6 ACPH office with a pre-symptomatic individual nearby may encounter enough exposure
to develop a Minor Illness that is "cold like" in around 11 hours.
https://www.medrxiv.org/content/10.1101/2020.10.03.20206110v1
Testing mobile air purifiers in a school classroom:
Reducing the airborne transmission risk for SARS-CoV-2
In times when classes were conducted with windows and door closed,
the aerosol concentration was reduced by more than 90% within less than 30 minutes
when running the purifiers (air exchange rate 5.5/hr).
https://www.medrxiv.org/content/10.1101/2020.10.02.20205633v2
The FDA has issued a warning letter to Texas-based KetoKerri,
citing a series of false and misleading statements by the company relating to its supplements,
including the suggestion that customers drink "a mixture of chlorine dioxide and water
for the prevention and treatment of COVID-19, among other diseases."
https://www.fdanews.com/articles/199364-fda-reprimands-texas-firm-for-false-covid-19-claims
A contact tracing study presented at this year's ESCMID Conference on Coronavirus Disease
(ECCVID) confirms the effectiveness of wearing of masks in public, handwashing,
and social distancing to protect against SARS-CoV-2
Florida drops COVID-19 restrictions with 700,000 cases and 14,000 dead
Florida Governor Ron Insane Friday scrapped COVID-19 restrictions on bars and restaurants
Restaurants may not be limited by any local government COVID-19 emergency order
"to less than 50% of their indoor capacity."
https://medicalxpress.com/news/2020-09-florida-covid-restrictions-dead.html
SARS-CoV-2 could infect a broad range of vertebrates, which could serve as
reservoirs of the virus, supporting future anthroponotic and zoonotic transmission.
https://www.nature.com/articles/s41598-020-71936-5
Three antigen-detecting, rapid point-of-care diagnostics for SARS-CoV-2
were assessed for performance, limit of detection and ease-of-use.
The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76.6%
[95% Confidence Interval (CI) 62.8-86.4] sensitive and 99.3% [CI 98.6-99.6] specific.
A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by
STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC.
Bioeasy and Coris showed specificity of 93.1% [CI 91.0%-94.8%] and 95.8%
[CI 93.4%-97.4%], respectively, not meeting the predefined target of =98%.
Conclusion:
There is large variability in performance of Ag-RDT tests with one test showing promise.
SARS-CoV-2 encoded proteins and some anti-COVID-19 drugs currently used can induce
lytic reactivation of Kaposi sarcoma-associated herpesvirus (KSHV),
a major human oncogenic virus, through manipulation of intracellular signaling pathways.
[ cure worse than disease ]
https://www.biorxiv.org/content/10.1101/2020.10.02.324228v1
"November 25 is the time we will have enough safety data to be able to put into an EUA file
that we would send to the FDA
- assuming that the safety data is good, i.e. a vaccine is deemed to be safe"
Mandatory vaccination has proven effective in ensuring high childhood immunization rates
in many high-income countries.
However, except for influenza vaccination of health care workers,
mandates have not been widely used for adults.
https://www.nejm.org/doi/full/10.1056/NEJMp2020926
COVID-19 antibodies in donated plasma decline within first months after symptom onset
Nearly 7% of the original 282 donors did not have detectable antibodies at their first donation
and this proportion doubled in donors who waited more than 11 to 12 weeks
https://www.biorxiv.org/content/10.1101/2020.07.16.206847v1.full.pdf
EUA for OralDNA Labs' coronavirus saline oral rinse test, OraRisk,
a COVID-19 real-time polymerase chain reaction test alternative to nasal swab and saliva direct testing.
The product identifies nucleic acid from SARS-CoV-2 in culture specimens.
Samples can remain viable for up to 72 hours
and they do not need to be transported under refrigeration.
Nuclear factor erythroid 2-related factor 2 (NRF2) agonists
4-Octyl-itaconate (4-OI) and dimethyl fumarate (DMF)
are broadly effective in limiting virus replication
and in suppressing pro-inflammatory responses of SARS-CoV2.
https://www.nature.com/articles/s41467-020-18764-3
LabCorp has received an EUA for RT-PCR test
using heat instead of chemical reagents that are in short supply.
It also received an EUA for pooled testing of samples collected at home.
Developed in partnership with government agencies and at least $70 million from U.S. taxpayers,
best evidence shows remdesivir reducing hospital stays from 15 to 11 days
but not significantly improving odds of surviving COVID-19.
The FDA agreed with Gilead's request to start using its Nordic-sounding brand name, Veklury,
and the company is on track to make more than $9 billion on the drug in 2020 and 2021,
at the $3,120 price endorsed by the Trump administration,
according to an estimate by a Credit Suisse investment analyst.
Nine in ten recovered COVID-19 patients experience side-effects
Fatigue was the most common side-effect with 26.2%,
followed by difficulty in concentration which had 24.6%.
Other after-effects included psychological or mental side-effects and loss of taste or smell.
Some states will receive 6.5 million BinaxNOW rapid coronavirus tests this week
All told, 100 million of the Abbott tests will eventually be sent to states.
Another 50 million of the tests will go to nursing homes, assisted-living facilities
and historically black colleges and universities.
"We don't know anything about these tests' efficacy in asymptomatic patients,"
said Dr. Krutika Kuppalli, an infectious disease physician at the Medical University of South Carolina.
There had been no clear guidance on how results of tests performed
outside the health care system would be reported to officials trying to track the virus's spread.
https://www.nytimes.com/2020/09/28/health/trump-coronavirus-testing-rapid.html
CDC credibility has eroded when most needed
Inside the CDC, staffers acknowledge Redfield's limitations as a leader but are fearful that,
if he is ousted or quits, the White House will install someone of a more distinctly political
or ideological bent, such as Scott Atlas, a Stanford University neuroradiologist,
who has said pandemic fears are overblown, has become a Trump favorite
and has publicly criticized Redfield in recent days.
As the only flying mammals, bats expand huge amounts of energy,
eventually damaging their DNA, to which they have adapted
by dampening immune responses to DNA damage, increasing tolerance to RNA viruses
Bats often range over wide territories,
potentially picking up more varieties of viruses than other mammals.
In many bat species, millions of animals roost together, easing virus spread
Enzyme-linked immunosorbent assay (ELISA) is lower risk than working with live viruses.
Sample are tested on a plate impregnated with angiotensin-converting enzyme 2 (ACE2),
the human receptor protein to which SARS-CoV-2 attaches when invading cells.
Researchers then add a solution containing the viral spike protein fragment that can bind to ACE2.
If binding takes place, an enzyme turns the solution blue and then yellow, but
samples with antibodies against SARS-CoV-2 prevent binding, blocking the colorful reaction.
Small drug molecules can penetrate tissue very well and be administered as pills.
However, these small molecules are not highly specific, can bind to many human proteins
and cause side effects.
Large biological drug molecules, including naturally occurring antibodies, by contrast,
do not penetrate tissue very well.
Antibody treatments must also be administered intravenously in a doctor's office.
The advantage is that antibodies are highly specific.
They do not interfere with other human proteins and rarely cause side effects.
Q: Can you talk about the pressure that you've felt, personally, to develop this vaccine?
A: I had moments that I needed a glass of wine - let me put it that way.
Sorrento releases preclinical data for STI-1499 and STI-2020
demonstrating potent neutralizing activity against SARS-CoV-2.
"Based on the preclinical testing we have conducted to date,
STI-2020 is our most promising SARS-CoV-2 antibody so far."
Sorrento has FDA clearance for its STI-1499 Phase 1 clinical trial
in hospitalized COVID-19 patients and intends to submit an IND for STI-2020 soon.
Targeting the SARS-CoV-2 RNA Genome
with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders
"Our concept was to develop lead medicines capable of breaking COVID-19's clutch.
We put the frameshifting element into cells
and showed that our compound binds the element and degrades it. The next step will be
to do this with the whole COVID virus, and then optimize the compound."
https://pubs.acs.org/doi/abs/10.1021/acscentsci.0c00984
Additive model-based bivariate causal discovery for scalar factors
and multivariate Granger causality tests for time series factors
were applied to the surveillance data of lab-confirmed U.S COVID-19 cases,
University of Maryland Data (UMD) data, and Google mobility data
from March 5, 2020 to August 25, 2020 in order to evaluate
social-biological factors, economics, Google mobility indexes, and virus test rate
contributions to COVID-19 new case and death counts.
Active cases/1000 people, workplaces, tests done/1000 people, imported COVID-19 cases,
unemployment rate and unemployment claims/1000 people,
mobility trends for places of residence (residential), retail and test capacity
were the most significant risk factor for new COVID-19 cases
in 23, 7, 6, 5, 4, 2, 1 and 1 states, respectively.
No metrics showed significant evidence in mitigating the COVID-19 epidemic in FL.
Only a few metrics showed evidence in reducing new cases in AZ, NY and TX.
https://www.medrxiv.org/content/10.1101/2020.09.29.20203505v1
A new, portable lab-on-a-chip can identify concentrations of COVID-19 antibodies.
The miniature ELISA achieves results using 8 microliters of blood in 15 minutes,
while standard ELISA may require days for results using 100 microliters.
https://www.sciencedirect.com/science/article/pii/S0956566320305649
Researchers in India found that 71% of individuals with COVID-19
did not infect any of their contacts, while a mere 8% of infected individuals
accounted for 60% of new infections.
Chances of a person with COVID-19, regardless of their age,
passing it on to a close contact ranged from 2.6% in the community to 9% in the household.
Children and young adults, who made up one-third of COVID cases,
were especially key to transmitting the virus.
https://science.sciencemag.org/content/early/2020/09/29/science.abd7672
catalase, a low cost naturally occurring antioxidant enzyme,
is a potential COVID-19 therapy
"our research suggests this enzyme could offer a very effective therapeutic solution
for treatment of hyperinflammation that occurs due to SARS-CoV-2 virus,
as well as hyperinflammation generally." Experiments showed that catalase can
repress SARS-CoV-2 virus replication in rhesus macaques without noticeable toxicity.
https://onlinelibrary.wiley.com/doi/10.1002/adma.202004901
Conversation quickly spreads droplets inside buildings
ordinary conversation creates a conical 'jet-like' airflow that quickly carries
a spray of tiny droplets from a speaker's mouth across meters of an interior space.
https://www.pnas.org/content/early/2020/09/24/2012156117
Ventilation systems in many modern office buildings,
which are designed to keep temperatures comfortable and increase energy efficiency,
may increase the risk of exposure to the coronavirus, particularly during the coming winter.
Widely-used 'mixing ventilation' systems, designed to keep conditions uniform
in all parts of the room, disperse airborne contaminants evenly throughout the space.
VirScan, a tool designed to detect in a drop of blood
which of more than 1,000 different viruses have infected a person,
can now also detect evidence of infection from coronaviruses,
including SARS-CoV-2. In the case of SARS-CoV-2,
the team detected a range of antibody frequencies against various epitopes.
Many were public epitopes
- regions recognized by the immune systems of large numbers of patients.
One public epitope was recognized by 79% of COVID-19 patients.
Others are considered private and recognized by only a few or even one individual.
Ten epitopes were in regions essential for viral entry
and are likely recognized by neutralizing antibodies.
The team used the most discriminatory epitopes to develop a rapid diagnostic test.
https://science.sciencemag.org/content/early/2020/09/28/science.abd4250
The Coyote Flash 20 "is currently the fastest machine in the world" for COVID-19 PCR tests.
Between February and July, 500,000 tests were carried out in China using the Flash 20,
with results 97% the same as those returned by conventional PCR testing in a lab.
https://medicalxpress.com/news/2020-09-chinese-company-global-sales-quick.html
A new Duke University-led analysis shows that during the early months of the pandemic,
the average number of new infections caused by an infected individual
(i.e. the basic reproduction number, R0) was 4.5, or more than twice as many
as the initial 2.2 rate estimated by the World Health Organization at the time.
At 4.5, governments had just 20 days from first reported cases
to implement non-pharmaceutical interventions stringent enough
to reduce the transmission rate to below 1.1 and prevent widespread infections and deaths.
New analysis estimates that achieving herd immunity from COVID-19
requires 78% of a population to no longer be susceptible.
On September 12, the U.S. hit a recent low in its seven-day case average of around 35,000.
As of September 26, it was back up to almost 45,000. States are rolling back restrictions,
people are eager to get back to normal, and Thanksgiving and Christmas are coming up,
risking yet another surge in the COVID-19 epidemic.
Saliva tests could detect the silent carriers of COVID-19
In this mass-screening study including 1,924 individuals,
the sensitivity of nucleic acid amplification testing
with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%)
and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1388/5911780
Regular COVID-19 testing for groups most likely to spread the virus
more efficient, cost-effective than random testing.
"certain groups, such as healthcare and social care workers
that are in frequent close contact with others,
are more likely to pass on COVID-19 than other groups,
for example those working from home"
https://medicalxpress.com/news/2020-09-regular-covid-groups-virus-efficient.html
Older persons are underrepresented in COVID-19 treatment and vaccine trials.
Globally, persons older than 65 years comprise 9% of the population,
yet account for 30% to 40% of COVID-19 cases and more than 80% of deaths.
Of 18 vaccine trials, 11 (61%) included age cut-offs, and the remaining 7 had broad
nonspecified exclusions; thus, 100% were considered high risk for excluding older adults.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771091
Using segmented regression, with correlation coefficients ranging from 92% - 99%,
school closings dropped infection rates in half, lockdowns dropped the rates 3 to 4 fold, and
other actions (such as closing bars and mandating masks) brought rates even further down.
Hospitalizations and deaths paralleled cases, with lags of three to ten days.
https://www.medrxiv.org/content/10.1101/2020.09.26.20202457v1
Patterns in complete blood count changes, including new cell activation parameters,
from 982 confirmed COVID-19 adult patients formed the basis to develop
a multi-parameter prognostic score to predict, during the first three days after presentation,
which patients will recover without ventilation or deteriorate within a two-week timeframe.
https://www.medrxiv.org/content/10.1101/2020.09.27.20202168v1
At home, open the windows or buy an air filter.
Elsewhere, minimize time indoors;
wearing a face covering and washing your hands are still the best ways to protect yourself.
While they do not offer full protection,
masks may potentially reduce the amount of virus inhaled by a wearer.
"We think that masks reduce that dose of virus that you inhale
and, thereby, drive up rates of asymptomatic infection."
https://www.nejm.org/doi/full/10.1056/NEJMp2026913
"these two papers explain nearly 14% of severe COVID-19 cases"
For a significant minority of patients with serious COVID-19,
the interferon response has been crippled by genetic flaws
or by rogue antibodies that attack interferon itself.
94% of patients with interferon-attacking antibodies were male.
"at least 10% of critical COVID-19
is an autoimmune attack against the immune system itself"
https://science.sciencemag.org/content/369/6511/1550
Ultrapotent antibody mix from recovered patients blocks COVID-19 virus attachment
Researchers determined how the antibodies worked on a molecular level
through cryo-electron microscopy studies of the resulting changes
in the configuration of the virus infection machinery.
Besides directly preventing interactions with the host receptor,
one of the two discovered antibodies locks the infection machinery in an inactive conformation,
meaning it could not fuse with the host membrane on the surface of the cell.
If unable to fuse, the coronavirus cannot break in and deliver its RNA to commandeer the cell.
https://science.sciencemag.org/content/early/2020/09/23/science.abe3354
Adequate levels of vitamin D reduce COVID-19 complications
Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed
to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239799
A new diagnostic tool uses glycans (sugars) to detect the SARS-COV-2 virus,
instead of its proteins, using a tool very similar to a home pregnancy test,
is being developed by the University of Warwick and its partner Iceni Diagnostics
snf may allow on-the-spot detection of Coronavirus infection,
without facilities using a simple disposal device.
https://pubs.acs.org/doi/10.1021/acscentsci.0c00855
Laboratory tests of surgical and N95 masks by researchers at the University of California, Davis,
show that they do cut down the amount of aerosolized particles emitted during breathing, talking and coughing.
Tests of homemade cloth face coverings, however,
show that the fabric itself releases a large amount of fibers into the air,
underscoring the importance of washing them.
https://www.nature.com/articles/s41598-020-72798-7
In an update to July 31 item, recent live subject research corroborates initial thoughts
about the efficacy of
remdesivir administration through dry powder inhalation.
"The live subject tests further show our initial thoughts: it is preferable to keep remdesivir
in the lungs where it is converted from the prodrug to the active GS-441524
rather than through other comparable delivery methods. One of our dry powder formulations
had very low plasma concentration of remdesivir following administration to the lung,
meaning that remdesivir stayed in the lung where the infection is primarily located."
TFF Pharmaceuticals has acquired the patents regarding thin-film freezing and inhalation.
Pharmacies brace for flu shot demand surge
Rite Aid has purchased 40% more influenza vaccines than other years.
Walgreens has also increased its flu vaccine stockpile this year,
anticipating a 30% to 50% jump in customers who will want flu shots or other immunizations
https://www.statnews.com/2020/09/25/flu-shots-covid-19-pandemic-demand/
Dr. Randall Williams, director of the Department of Health and Senior Services,
said he still isn't recommending Parson impose a mask mandate across the state,
arguing that the state's diversity would make it untenable.
"One size doesn't fit all," Williams said. "If you are too draconian about it,
it's almost as if it creates more problems than it solves."
Pandemic school funding debate in South Carolina rekindles Jim Crow-era controversy
This summer Education Secretary Betsy DeVos attempted to direct
a large share of the $13.5 billion in federal coronavirus relief to private schools.
Thwarted by U.S. District Court, she directed large sums of CARES Act dollars
into the Governor's Emergency Education Relief Fund. SC governor Henry McMaster
announced he would take $32 million of his $48.5 million education discretionary fund
to provide tuition grants for students at private schools.
Trudeau: Canada already in second wave of coronavirus in 4 largest provinces
Canada saw an average of 1,123 cases reported daily during the past seven days,
compared to just 380 cases reported per day in mid-August.
Canada's top doctor warned this week that the only way to prevent
acceleration of the spread is if everyone works to put on the brakes.
https://globalnews.ca/news/7354511/canada-coronavirus-second-wave-justin-trudeau/
University of Rochester Medical Center evaluates Abbott's $5 BinaxNOW COVID-19 card
Results of testing from all 19 sites indicated that the test
correctly diagnosed a coronavirus infection 97.1% of the time (sensitivity of 97.1%)
and correctly returns a negative test result 98.5% of the time (specificity of 98.5%).
"this far exceeded what anyone expected from a lateral flow test."
Abbott will ship "tens of millions of tests" for COVID-19 this month,
ramping up to 50 million tests a month at the beginning of October.
FDA issues point-of-care EUA for Assure COVID-19 IgG/IgM Rapid Test Device finger-stick
"Until today, serology test samples were generally only able to be evaluated in a central lab,
which can be time-consuming and use additional resources
to transport samples and run the test."
https://www.fda.gov/media/139792/download
In the race for a COVID-19 vaccine, slow starters could still win out
Corporate giants Sanofi and Merck, got relatively late starts developing COVID-19 vaccines,
but have such deep experience developing and testing vaccine candidates
and producing vaccine at commercial scale,
that both could well close the gap considerably in the months ahead.
Each is developing two vaccines, in partnership with others.
ECRI tested nearly 200 masks from 15 different manufacturer models
purchased by some of the largest health systems in the country.
There was not only variability among the different brands
but also inconsistencies among masks made by the same manufacturer.
In April, the FDA issued an umbrella emergency use authorization
for masks that are manufactured in China and not approved by the
National Institutes of Occupational Safety and Health (NIOSH).
The agency reissued the order in June.
Johnson & Johnson JNJ-78436735 adenovirus vaccine phase 3 trial begins.
Storage requires refrigeration, but it does not need to be stored in subzero temperatures,
and it may require just one dose instead of two. Johnson & Johnson has previously used
adenovirus to make vaccines for Ebola, H.I.V., respiratory syncytial virus and Zika.
AstraZeneca's vaccine is based on a different adenovirus.
White blood cells called monocytes released into the blood from bone marrow
have abnormal features in COVID-19 patients, and treatments preventing their release from bone marrow
may reduce exaggerated immune responses that contribute to poor outcomes in severe COVID-19.
https://immunology.sciencemag.org/content/5/51/eabd6197
A faster, simpler and accurate COVID-19 diagnostic that completely circumvents
the RNA-extraction procedure, so that once inactivated by heating,
rendering virus particles no longer infectious, samples in a simpler buffer medium
pass straight to a diagnostic reaction that detects virus' presence.
https://www.nature.com/articles/s41467-020-18611-5
Johns Hopkins publishes a COVID-19 outcome prediction model
[ based on my age and condition, entering a hospital
might put me at 6% probability of severe disease or death by 7 days ]
https://rsconnect.biostat.jhsph.edu/covid_predict/
based on age, body mass index (BMI), lung health and chronic disease, as well as
vital signs and the severity of a patient's COVID-19 symptoms at the time of admission.
Analyses were done by using R, version 3.6.2.
https://www.acpjournals.org/doi/10.7326/M20-3905
The host interactome is the network map of all protein-protein interactions inside cells.
Host interactomes show a limited number of high-powered hubs,
where a protein has a large number of connections,
and a limited number of important bottlenecks,
which are sites with a large number of short paths to a node.
These are key targets for pathogens as they seek to seize control,
rewiring an infected cell's flow of information and causing disease.
University of Alabama at Birmingham researchers have now built
the lung-epithelial cell host interactome integrated with a SARS-CoV-2 interactome.
Applying network biology analysis tools to this human/SARS-CoV-2 interactome
has revealed potential molecular mechanisms of pathogenesis for SARS-CoV-2.
https://www.cell.com/iscience/fulltext/S2589-0042(20)30718-5
COVID-19 dynamics across the U.S.: human mobility and social behavior
A deep learning model is trained on Google and Unacast mobility data spanning a period of 66 days,
and is able to yield accurate future forecasts of COVID-19 spread in 203 U.S. counties
within a time-window of 15 days. Code and data accompanying this manuscript are
[not yet] available at https://github.com/PredictiveIntelligenceLab/DeepCOVID19.
https://www.medrxiv.org/content/10.1101/2020.09.20.20198432v1
Jay Butler, the CDC's deputy director for infectious disease misinformation,
said the Friday update was posted in error.
"Unfortunately an early draft of a revision went up without any technical review," he said.
[ where "technical" means "political" ]
The edited Web page has removed all references to airborne spread, except for
a disclaimer that recommendations based on this mode of transmission are under review.
"We are returning to the earlier version and revisiting that process," Butler said.
"It was a failure of process at CDC."
Mathematicians Nick James and Max Menzies have published in the journal Chaos,
published by the American Institute of Physics, what they believe is
the first analysis of U.S. COVID-19 infection rates to identify
turning points in data that indicate when surges have started or ended.
https://aip.scitation.org/doi/10.1063/5.0024204
"In some of the worst performing states,
it seems that policymakers have looked for plateauing or slightly declining infection rates.
Instead, health officials should look for identifiable local maxima and minima,
showing when surges reach their peak and when they are demonstrably over."
New York and New Jersey completely flattened their infection curves
by the end of July with just a single surge. Thirteen states, including Georgia,
California and Texas, have a continuing and rising single infection surge.
Thirty-one states had an initial surge followed by declining infection
to be followed by a second surge. These states include Florida and Ohio.
https://phys.org/news/2020-09-covid-mathematicians.html
Weather impact on airborne coronavirus survival
"We found high temperature and low relative humidity lead to high evaporation rates
of saliva-contaminated droplets, thus significantly reducing the virus viability,"
https://aip.scitation.org/doi/10.1063/5.0024272
Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
Using electron cryo-microscopy (cryo-EM)
to analyse SARS-CoV-2 Spike at near atomic resolution,
researchers revealed a small molecule, linoleic acid (LA),
buried in a tailor-made pocket within the Spike protein.
A free fatty acid, LA is indispensable for many cellular functions.
The human body cannot produce LA.
Instead, the body absorbs this essential molecule through diet.
Intriguingly, LA plays a vital role in inflammation and immune modulation,
which are both key elements of COVID-19 disease progression.
"Our discovery provides the first direct link between LA,
COVID-19 pathological manifestations and the virus itself."
https://science.sciencemag.org/content/early/2020/09/18/science.abd3255
MMR vaccine could boost immunity and may prevent infection from SARS-CoV-2,
for a limited period, because the vaccine carries small amounts of live, weakened viruses
that could train the body's immune system to fight multiple pathogens.
Washington University School of Medicine is the clinical coordinating center
for a phase 3 MMR international trial involving 30,000 healthcare workers.
https://www.precisionvaccinations.com/mmr-vaccination-may-prevent-covid-19
Consensus transcriptional regulatory networks of coronavirus-infected human cells
Publicly archived transcriptomic datasets were used to compute consensus regulatory signatures,
or consensomes, that rank human genes based on their rates of differential expression
in MERS-CoV (MERS), SARS-CoV-1 (SARS1) and SARS-CoV-2 (SARS2)-infected cells.
The Signaling Pathways Project (SPP) is an integrated knowledgebase
designed to assist bench researchers in leveraging publically archived transcriptomic
and ChIP-Seq datasets to generate research hypotheses.
SPP here predicted SARS2 genetic interactions
which have in part been subsequently corroborated by independent in vitro and in vivo studies.
https://www.nature.com/articles/s41597-020-00628-6
Another modified SEIR model that accounts for infection spread
during the latent period, infections from asymptomatic or pauci-symptomatic infected individuals,
potential loss of acquired immunity, people's increasing awareness of social distancing
and the use of vaccination as well as non-pharmaceutical interventions like social confinement.
https://www.medrxiv.org/content/10.1101/2020.09.19.20198051v1
A model from study of climate change negotiations and underwater giant kelp forest
was repurposed to evaluate local vs regional COVID-19 public health actions,
concluding that reopening schools and businesses in local areas
without active outbreaks can be as effective as a lengthy regional lockdown,
provided that when local cases begin to spike,
localities stay on top of the epidemic and cases imported by travellers.
[ FWIW, this sounds pretty much like Cuomo's reopening strategy for NY ]
Once tested, people may have to wait up to two weeks to learn if they have the virus.
Such delays defeat the purpose of trying to prevent further infections.
Prompt results from 6 million to 10 million tests a day are needed to control outbreaks.
Wastewater predicts COVID-19 outbreaks days before diagnostic testing
"If you take our smoothed curve for SARS-CoV-2 RNA in sewage sludge
and overlay it on the smoothed curves from testing, the trends are very similar
- but we're five to seven days ahead of it,"
https://www.nature.com/articles/s41587-020-0684-z
Initial Model for U.S. CoVID-19 Resurgence
1) the gradual increase in doubling time from society-wide shut-downs
is likely due to eliminating many population gathering points
that could have enabled CoVID-19 spread
2) a non-zero fast pandemic shutoff is likely due to more people wearing masks more often
https://www.medrxiv.org/content/10.1101/2020.09.16.20196063v1
SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism
(1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT)
with the 40S ribosomal subunit
(2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal
domain (NT) with the 5' untranslated region (5' UTR) of SARS-CoV-2 mRNA.
https://www.biorxiv.org/content/10.1101/2020.09.18.302901v1
"the strongest predictor of a country's mortality risk was its ratio of elderly people
- which surpassed all other socio-economic and demographic indicators."
https://www.mdpi.com/1660-4601/17/15/5592
Recombination should not be an afterthought
Writing in September 2020, the scientific consensus is that SARS-CoV-2
did not gain the ability to infect humans as the result of recombination with another virus.
In July, Boni et al.4 found that all loci of SARS-CoV-2 diverged within bat coronavirus lineages.
They were able to reach what seems to be the emerging scientific consensus for three reasons.
First, instead of focusing on the lineages of immediate interest,
they performed a broad phylogenetic analysis of 68 ancestral lineages.
Second, they used these trees to test hypotheses about the data.
Third, they explicitly searched for recombination breakpoints and directly modelled
distinct evolutionary processes, including recombination, that could explain their data.
This allowed them to offer their conclusions about recombination
on a foundation of statistical rigor.
https://en.wikipedia.org/wiki/Bayesian_inference_in_phylogeny
Dipeptidylpeptidase-4 is a key regulator of obesity and type 2 diabetes
In a survey, circulating levels of soluble Dipeptidylpeptidase-4
are reduced in patients hospitalized for severe COVID-19 infections.
The average age of COVID-19 patients was 66.29+/-11.70 and mean BMI was 24.26+/-2.31.
In healthy controls, the mean age was 62.43+/-9.43 and mean BMI was 24.22+/-4.04.
https://www.nature.com/articles/s41366-020-00689-y
WHO endorses phase 3 protocol for herbal medicine COVID-19 trials
"If a traditional medicine product is found to be safe, efficacious and quality-assured,
WHO will recommend (it) for a fast-tracked, large-scale local manufacturing,"
Prosper Tumusiime, a regional WHO director, was quoted as saying.
https://medicalxpress.com/news/2020-09-endorses-protocol-virus-herbal-medicine.html
three factors:
1) The summer's worst COVID-19 outbreaks have receded, reducing demand for tests.
2) Trump's administration recently recommended less testing, before backtracking this week.
3) state governments may not be reporting all tests within their borders,
particularly relatively newer antigen tests that are growing in use
Suppression of COVID-19 infection by isolation time control based on the SIR model
and an analogy from nuclear fusion research
In the SIR model, the second term (isolation term) in the differential equation
of the number of the infected is quite similar to the "helium ash particle loss term"
in deuterium-tritium (D-T) nuclear fusion. Based on this analogy,
we have found that isolation of the infected is not actively controlled in the SIR model.
If the confirmed case can be isolated in 3~8 days by widely performed testing,
this pandemic could be suppressed without awaiting vaccination.
If the mild outing restriction and vaccination are taken together,
the isolation control time can be longer.
We consider this isolation time control might be the only solution
to overcome the pandemic when vaccine is not available.
https://www.medrxiv.org/content/10.1101/2020.09.18.20197723v1
Mayo Clinic COVID-19 maps: easy-to-read graphics by state and county,
with test and fatality rate trend lines, using data from USAfacts and The COVID Tracking Project.
[ my issue with it: raw case counts, NOT per-capita; favoring low populations. ]
https://www.mayoclinic.org/coronavirus-covid-19/map
Moderna and Pfizer publish phase 3 trial protocols
Companies typically share these documents after their studies are complete.
The plan released by Moderna on Thursday morning included a likely timetable
that could reach into next year for determining whether its vaccine works
"They have opened up, for the first time, the ability for researchers not involved in the trial
to form their own independent judgment about the design of this study."
Structural basis for neutralization of SARS-CoV-2 by a potent therapeutic antibody
Humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2
and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations
by engaging the spike (S) receptor binding domain (RBD).
https://science.sciencemag.org/content/369/6510/1505
'Pandemic fatigue' leads to second wave in France and Spain
France and Spain are now seeing more new cases every day
than they did when the virus originally peaked in the spring.
"More than half of European countries have reported a greater-than-10% increase
in cases in the past two weeks. Of those countries, seven have seen
newly reported cases increase more than twofold in the same period."
CRISPR-based COVID-19 testing at point of care validated
The "All-In-One-Dual CRISPR-Cas12a" (AIOD-CRISPR) method enables
simple, rapid, ultrasensitive, visual detection of SARS-CoV-2,
intended for use at home or in small clinics.
https://www.nature.com/articles/s41467-020-18575-6
Study finds most homemade masks are doing a great job
"We found that all of the fabrics tested are considerably effective
at blocking the 100 nanometer particles carried by high-velocity droplets
similar to those that may be released by speaking, coughing and sneezing, even as a single layer.
With two or three layers, even the more permeable fabrics, such as T-shirt cloth,
achieve droplet-blocking efficiency that is similar to that of a medical mask,
while still maintaining comparable or better breathability."
https://www.sciencedirect.com/science/article/pii/S2352431620301802
Roche reports that tocilizumab, sold now as Actemra and RoActemra
for treating rheumatoid arthritis and some other diseases,
reduced COVID-19 patients needing a breathing machine or dying within 28 days
from 19% to 12% in a study of 389 participants of whom
about 85% were Hispanic, Black, Native American or other ethnic or racial minorities.
https://www.roche.com/investors/updates/inv-update-2020-09-18.htm
How We Survive the Winter: Live like you're contagious
For the past few weeks, the country has been averaging around 40,000 new infections per day.
Fauci said that "we must, over the next few weeks, get that baseline of infections
down to 10,000 per day, or even much less if we want to maintain control of this outbreak."
Vitamin D deficiency increases COVID-19 infection risk by more than 50%
In a study of more than 190,000 people who had been screened for COVID-19,
nearly 13% of those with lower-than-recommended levels of the nutrient
tested positive for the coronavirus.
Research suggests that up to 40% of people have vitamin D deficiency,
while up to 60% have insufficient levels of the nutrient. The only foods rich in vitamin D
are mushrooms exposed to sunlight, cod liver oil and wild-caught oily fish like salmon
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239252
[ This seemingly
important study
examines 3 branches of adaptive immunity ]
Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19
and associations with age and disease severity.
When the body detects a novel virus, "innate" defensive cells (which broadly attack any pathogen)
rally immediately and also release cytokines to alert adaptive immune cells:
1) antibodies that aim to attach to and "neutralize" the virus
2) killer T cells act as a backup, identifying and destroying any infected cells
3) helper T cells coordinate production of antibodies, killer T cells,
and other immune responses.
* Adaptive immune responses limit COVID-19 disease severity
* Multiple coordinated arms of adaptive immunity control better than partial responses
* CXCL10 may be a biomarker of impaired T cell responses in acute COVID-19
* Aging and scarcity of naive T cells may be linked risk factors for severe COVID-19
* Neutralizing antibody levels did not correlate with COVID-19 severity.
* Patients with the worst cases of COVID-19 had low levels of helper and killer T cells.
"It looks like T cells play a more important role than antibodies during natural infection"
Blood tests may not reflect the immune responses in tissues such as the lungs,
which is a key site of attack by the virus. "I don't know if monitoring the blood
is going to tell us what is going to prevent a mild case from becoming severe,"
"Eliciting both antibody and T cell responses with vaccines
is likely an important step to achieving efficacy against severe COVID-19," but
some of the vaccine efficacy trials aren't designed to even analyze T cell levels, and
training an immune system to make strong T cell responses against SARS-CoV-2
ultimately may require using more parts of the virus in a vaccine than the spike protein alone.
46-page PDF:
https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2931235-6
In a study to examine the entire binding mechanism between ACE2 and the spike protein,
researchers in Crick's Structural Biology of Disease Processes Laboratory have
characterized ten distinct structures associated with different stages of receptor binding and infection.
The opening process reduces S1 contacts and un-shields the trimeric S2 core,
priming fusion activation and dissociation of ACE2-bound S1 monomers.
https://www.nature.com/articles/s41586-020-2772-0
According to data scientists who created a machine-learning tool to analyze
the over 100,000 SARS-CoV-2 study publications,
basic lab-based studies on the microbiology of the virus,
including research on its pathogenesis and mechanisms of viral transmission, are lacking.
"the relative lack of lab-based studies seems to be unique to SARS-CoV-2" " This shortage
of lab-based research means that the scientific community may miss key aspects of the virus
that could impact our ability to contain this pandemic and to counter future ones."
https://medicalxpress.com/news/2020-09-analysis-covid-gaps.html
Proof that 222nm UV light effectively kills SARS-CoV-2
HU researchers showed that 99.7% of the SARS-CoV-2 viral culture was killed
after a 30-second exposure to 222 nm UVC irradiation at 0.1 mW/cm2.
A wavelength of 222 nm UVC cannot penetrate the outer, non-living layer of the human eye
and skin so it won't cause harm to the living cells beneath. This makes it a safer
but equally potent alternative to the more damaging 254 nm UVC germicidal lamps
increasingly used in disinfecting healthcare facilities.
https://www.ajicjournal.org/article/S0196-6553(20)30809-9/fulltext
Computer simulations analyze T-cell receptors' interactions with materials
presented by major histocompatibility complex (MHC) molecules on cell surfaces.
"there are hundreds of thousands of MHC molecules displaying peptides,
and only a few are from invading cells, if at all.
The rest of them are normal products of cellular metabolism,
which means the T-cell needs to be able to see that needle in the haystack."
It is almost impossible to see this interaction in atomic details experimentally.
"Only the simulation can see and analyze molecular motion under load.
A lab experiment doesn't have the resolution.
Experimentally determined atomic structures of proteins are static snapshots,
but when the molecule moves, you have basically no way to see the motion."
https://www.pnas.org/content/117/35/21336
T-705 (Favipiravir and Avigan) has broad-spectrum activity against a number of RNA viruses
and is currently licensed in Japan for use in the treatment of influenza virus.
COVID-19 treatment Clinical trials are currently ongoing in China, Italy, and the UK,
although its precise MoA against CoVs has not been shown.
Results here show that T-705 inhibits SARS-CoV-2 through lethal mutagenesis.
https://www.nature.com/articles/s41467-020-18463-z
Ebselen, disulfiram, carmofur, PX-12, tideglusib, and shikonin
are non-specific promiscuous SARS-CoV-2 main protease inhibitors.
This inhibition is abolished or greatly reduced with the addition of reducing reagent DTT.
https://www.biorxiv.org/content/10.1101/2020.09.15.299164v1
Because millions are now contracting COVID-19,
even a small proportion who suffer severe myocarditis would amount to a lot of people.
MRI heart scans of 100 COVID-19 patients an average of 71 days after they had tested positive
showed cardiac abnormalities in 78 people, with 60 appearing to have active inflammation.
https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916
Researchers want to learn
* how common heart inflammation is after COVID-19,
* how long it lingers,
* whether it responds to specific treatments
* whether patients fare similarly to those with myocarditis from other causes,
In more than half of virus-induced cases, the inflammation resolves without incident,
but some cases lead to arrhythmia and impaired heart function,
or, rarely, the need for a heart transplant.
Online annotated color-coded U.S. map for COVID-19 new case doubling time by county
[in trouble: Logan, CO; Chemung Oswego Ontario Tompkins Chenango, NY;
Colleton Richmond, SC; much of MO ]
A new machine learning-based online tool
developed by researchers at Massachusetts General Hospital (MGH),
Harvard Medical School (HMS), Georgia Tech and Boston Medical Center
allows for early detection of COVID-19 outbreaks in different U.S. counties.
The COVID-19 Outbreak Detection Tool is updated two-to-three times per week
and predicts how fast an outbreak is spreading within a given county
by estimating the doubling time of COVID-19 cases.
Infections are doubling in less than 1 week in Harrisonburg VA,
Wheeler GA, Monroe IN and Whitman WA.
CDC: U.S. should have enough COVID-19 vaccine to return to 'regular life' by 3Q 2021
Earlier in the day, the CDC outlined a sweeping plan
to make vaccines for COVID-19 available for free to all Americans.
In the plan, the agency said it anticipates a coronavirus vaccine
will initially be granted an emergency use authorization before a full formal approval.
Using a dual antigen ELISA-based approach that combines
data about IgG responses to both the Nucleocapsid and Spike-receptor binding domain,
antigens achieves near-optimal sensitivity and specificity.
Initial results suggest many more people have been exposed
to the virus in Australia than had been previously detected.
https://www.medrxiv.org/content/10.1101/2020.09.09.20191031v1
Federal judge rules PA gathering size limits unconstitutional
U.S. District Judge William S. Stickman IV found that the Wolf administration's policy
limiting indoor and outdoor gatherings and events to 25 and 250 people, respectively,
violates "the right of assembly enshrined in the First Amendment."
Up Is Down:
Pharmaceutical Industry Caution vs. Federal Acceleration of COVID-19 Vaccine Approval
From a legal perspective, CEO pledges to hold back on seeking marketing permission prematurely
could lead to the unusual situation of the government advocating for quick approval
of a medical product even as its manufacturer declines to request such approval.
Then what? The FDA process is predicated on a sponsor submitting an application to the agency.
But an administration that has taken an unprecedented role in influencing FDA policy on
COVID-19 could encourage the agency to issue an EUA for a product that has antibody data
that only seem promising, even without a formal approval request by its manufacturer.
This scenario is not out of the question:
in August, the Department of Health and Human Services
revoked the FDA's right to perform premarket review of laboratory-developed tests,
including COVID-19 diagnostics, reportedly over the FDA commissioner's objections.
Could Trump use the Defense Production Act (DPA) to compel a company to produce a vaccine
for which the manufacturer had not requested approval or for which approval was not granted?
https://www.nejm.org/doi/full/10.1056/NEJMp2029479
Labor Day: VA aftermath
Virginia reported a record 96 deaths related to COVID-19 on Tuesday,
shattering the previous one-day high of 57 deaths reported on May 28
Health department says high number is due to data backlog
Coronavirus Deaths Are Rising Right on Cue
Cases began to rise on June 16; a week later, hospitalizations began to rise.
Two weeks after that, 21 days after cases rose, states began to report more deaths.
That's the exact number of days that the Centers for Disease Control and Prevention
has estimated from the onset of symptoms to the reporting of a death.
https://www.theatlantic.com/health/archive/2020/07/second-coronavirus-death-surge/614122/
Canada on Friday reported no new COVID-19 deaths
Fever screening: neither sensitive nor specific.
"using fever as a screening tool for COVID-19 may provide a false sense of security"
Temperature checks were first deployed in January amid China's
"throw everything at the wall and show the world we've got this locked down"
attempt to stop the virus.
While a fever is one of the most common symptoms for people who do get sick,
a minority of hospital patients admitted with the virus had a fever.
COVID-19 is contagious before any symptoms appear,
and many infected people never develop any symptoms.
SARS-CoV-2 uses heparan sulfate to get inside cells
University of California San Diego School of Medicine researchers have discovered that
SARS-CoV-2 can't grab onto ACE2 without a carbohydrate called heparan sulfate.
The team demonstrated two approaches that can reduce the ability of SARS-CoV-2
to infect human cells cultured in the lab by approximately 80 to 90%:
1) removing heparan sulfate with enzymes or
2) using heparin as bait to lure and bind the coronavirus away from human cells.
https://phys.org/news/2020-09-covid-virus-heparan-sulfate-cells.html
University of Texas at Austin have developed a COVID-19 antibody test
that they claim is more accurate and efficient than the standard antibody tests
currently available and can handle hundreds of samples in a single run.
"We can now use highly scalable, automated testing
to examine antibody-based immunity to COVID-19 for hundreds of donors in a single run."
Failure to "flatten the coronavirus curve" in the U.S.
could lead to even more deaths than previously believed.
Previous research showing that death rates rise as ICUs handle more COVID-19 patients;
New finding is that constraints in available capacity of non-ICU beds
may have a spillover effect to non-hospitalized patients.
https://link.springer.com/article/10.1007/s11606-020-06084-7
University of Pittsburgh School of Medicine scientists have isolated
the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus
This antibody component, 10 times smaller than a full-sized antibody,
has been used to construct a drug, known as Ab8,
for potential use as a therapeutic and prophylactic against SARS-CoV-2.
https://www.upmc.com/media/news/091420-mellors-dimitrov-covid-ab8
Germany aims to reach herd immunity through a voluntary coronavirus vaccine
expected to be widely available by mid-2021. "We need 55 to 65% of the population to get vaccinated
to reach what is known as herd immunity and I firmly believe we can achieve this voluntarily"
The German government was offering around 750 million euros ($890 million) in funding
to help 3 domestic firms with their vaccine research and development.
https://medicalxpress.com/news/2020-09-germany-eyes-voluntary-covid-vaccine.html
A new ELISA microplate assay quantifying SARS-CoV-2 nucleocapsid antigen (N-antigen)
in serum or plasma could provide a valuable new alternative to PCR for COVID-19 diagnosis,
only requiring a blood draw and easily scalable in all clinical laboratories.
https://www.medrxiv.org/content/10.1101/2020.09.14.20191759v1
Are we there yet? An adaptive SIR model for
continuous estimation of COVID-19 infection rate and reproduction number in the U.S.
A simple method for estimating the time-varying infection rate and reproduction number R_t
using a sliding window approach applied to a Susceptible-Infectious-Removed model.
https://www.medrxiv.org/content/10.1101/2020.09.13.20193896v1
States with case growth >= 5%:
Alaska, Arkansas, Connecticut, Delaware, Maine, Nebraska, New Hampshire, New Jersey, Rhode Island, Wisconsin and Wyoming.
Oak Ridge National Laboratory probes SARS-CoV-2 spike proteins using neutron reflectometry
Neutrons are capable of probing biological materials under physiological conditions
without damaging them. The team first synthesized a lipid membrane
that mimics the outer membrane of cells that line the surfaces inside human lungs,
where this viral infection can take place.
Employing the liquids reflectometer (LIQREF) at ORNL's Spallation Neutron Source,
researchers spread the lipid membrane atop a thin layer of water in an apparatus called a Langmuir trough.
They then introduce the SARS-CoV-2 spike S2 subunit to these membranes
to observe in detail how the S2 and lipid membranes change shape when they interact.
Neutrons are sensitive to the element hydrogen, common to all biological molecules, and its isotopes.
By replacing some hydrogen atoms with deuterium atoms,
scientists can create contrast in their samples and selectively zero in on different structural features.
https://phys.org/news/2020-09-neutrons-probe-biological-materials-insights.html
"SARS-Cov-2 uses transmembrane serine protease 2 (TMPRSS2) to facilitate entry and spread in the body.
The degree to which a person expresses TMPRSS2 may affect how easy it is for the virus to get in and spread.
We found that nasal expression of TMPRSS2 was significantly higher in Blacks
than in Asians, Latinos, those of mixed race/ethnicity, and Whites."
https://jamanetwork.com/journals/jama/fullarticle/2770682
Baylor College of Medicine licences its recombinant protein vaccine candidate
to India-based biotechnology company Biological E. Limited (BE)
to develop a COVID-19 vaccine. Baylor has been working on a recombinant protein
vaccine candidate for SARS viruses since the original outbreak in 2003
https://www.bcm.edu/news/baylor-and-biological-e-limited-team-up-for-a-global-covid-19-vaccine
Saline mouth rinse/gargle samples demonstrated the highest combined user acceptability ratings
and analytical performance when compared with saliva and HCW collected NP swabs.
This sample type is a promising swab-independent option,
particularly for outpatient self-collection in adults and school aged children.
https://www.medrxiv.org/content/10.1101/2020.09.13.20188334v1
Sensing of COVID-19 antibodies in seconds
via an electrochemical platform consisting of gold micropillar array electrodes
decorated with reduced graphene oxide and functionalized with recombinant viral antigens.
The array electrodes are fabricated by Aerosol Jet (AJ) nanoparticle 3D printing,
where gold nanoparticles (3-5nm) are assembled in 3D space, sintered,
and integrated with a microfluidic device.
https://www.medrxiv.org/content/10.1101/2020.09.13.20193722v1
Digital contact tracing (DCT) cannot bring the reproductive number below 1
unless nearly the entire population uses the DCT system
and strictly follows quarantining and testing protocols.
When DCT is deployed in a population with an ongoing outbreak
where O(0.1%) of the population have already been infected,
the gains of the DCT intervention come at the cost
of requiring up to 15% of the population to be quarantined
(in response to being traced) on average each day for the epidemic's duration,
even when there is sufficient testing capability to test every traced person.
https://www.medrxiv.org/content/10.1101/2020.09.13.20192682v1
Policy intervention (`lockdown') and reductions in individuals' mobility are the major predictors
of SARS-CoV-2 transmission rates, but in their absence lower temperatures
and higher population densities are correlated with increased SARS-CoV-2 transmission.
Our results show that summer weather cannot be considered a substitute for mitigation policies,
but that lower autumn and winter temperatures may lead to an increase in transmission intensity
in the absence of policy interventions or behavioural changes.
https://www.medrxiv.org/content/10.1101/2020.09.12.20193250v1
Prior to significant public health interventions, reproductive numbers for 10 of 15 distinct
SARS-CoV-2 outbreaks have median posterior estimates ranging between 1.4 and 2.8.
Genomic results indicate that for 7 of the populations studied,
the number of recorded cases is much bigger than the estimated cumulative case counts,
suggesting the presence of unsequenced pathogen diversity in these populations.
https://www.medrxiv.org/content/10.1101/2020.09.12.20193284v1
South Carolina Department of Health and Environmental Control (DHEC) launches a new [dis]information system
"With COVID-19's continued prevalence across our state,
one of the few things we can do to protect ourselves from this deadly virus
is stay as healthy as possible and avoid contracting vaccine-preventable diseases
like mumps, measles, chicken pox and whooping cough.
SIMON provides immunization providers access to an individual's comprehensive immunization record."
Trump appointees meddle with CDC Coronavirus Reports
Caputo defended his team's reviewing CDC reports. "Our intention is to make sure
that evidence, science-based data drives policy through this pandemic
- not ulterior deep state motives in the bowels of CDC"
Pandemic spawns 'infodemic' in scientific literature
[ you read it here first ]
The average time to perform peer review and publish new articles has shrunk;
for virology, the average dropped from 117 to 60 days.
https://www.cell.com/patterns/fulltext/S2666-3899(20)30135-5
31 coronavirus cases announced in Beaufort Co. Saturday
Since mid-August, the county has reported fewer daily cases,
but the number of COVID-19 tests conducted in the area has also dropped.
At USC's Columbia campus, hundreds of students have been diagnosed with COVID-19.
https://www.islandpacket.com/news/coronavirus/article245683090.html
AstraZeneca and Oxford University AZD1222 COVID-19 vaccine candidate trial resuming
after being paused due to serious neurological illness in a UK patient.
Neither information about the patient's illness nor resumption rationale has been disclosed.
https://www.bbc.com/news/uk-54132066
Children who caught the coronavirus at day cares and a day camp
spread it to their relatives, according to a new report.
Researchers from Utah and the CDC focused on three outbreaks in Salt Lake City
child care facilities between April and July. Two were child-care programs for toddlers,
and the other was a camp for older kids. Their average age was about 7.
The study concluded 12 children caught the coronavirus at the facilities and spread it
to at least 12 of the 46 parents or siblings that they came in contact with at home.
Three of the infected children had no symptoms.
https://medicalxpress.com/news/2020-09-kids-infected-day-coronavirus-home.html
COVID-19 spreading in the U.S. weeks earlier previously suspected
Respiratory failure hospitalizations spiked in late December last year
and remained above historic levels for the next 10 weeks.
"This is consistent with the growing body of data
that suggests that there's been community spread much earlier than we had anticipated"
evolutionary genomics and computer simulation reconstruct SARS-CoV-2 spread
Because the SARS-CoV-2 evolutionary rate is slower than its transmission rate,
many identical genomes are rapidly spreading. This genetic similarity places limitations
on some inferences such as calculating the ratio of imported cases to local transmissions in a given area.
The value of detecting cases early, before they have bloomed into an outbreak,
cannot be overstated in a pandemic situation.
https://science.sciencemag.org/content/early/2020/09/09/science.abc8169
A City University of Hong Kong research team has successfully produced graphene masks
with an anti-bacterial efficiency of 80%,
which can be enhanced to almost 100% with exposure to sunlight for around 10 minutes.
Initial tests also showed very promising results in deactivating 2 species of coronaviruses.
The graphene masks are easily produced at low cost, and can help to resolve
the problems of sourcing raw materials and disposing of non-biodegradable masks.
https://pubs.acs.org/doi/10.1021/acsnano.0c05330
The U.S. now reports about 100,000 fewer daily tests than it did in late July
Millions of antigen tests are missing from the public data. Only six states,
representing 50 million people, make separate antigen-test data readily available.
Those data show that a mere 215,000 antigen tests have been reported since early August,
when they first appeared on state dashboards.
Even if the data are taken as representative of the U.S. as a whole, and scaled accordingly,
they imply that only 1.4 million antigen tests have ever been conducted
- far fewer than the number of tests that companies have shipped since June,
which is on the order of tens of millions.
killer T cells, key immune cells in fighting viral infections,
are present at much lower levels in COVID-19 patients,
compared to influenza or glandular fever. "The magnitude of the killer T cells
was only five times higher than those of the naïve immune cells. To give that perspective,
it's 10 times lower than what we see during an influenza or glandular fever response."
https://www.pnas.org/content/early/2020/09/09/2015486117
Two British companies are preparing to launch a simple COVID-19 saliva screening test
that aims to provide an accurate result within 20 seconds.
The Virolens device, developed by iAbra and manufactured by TT Electronics,
uses a digital microscope and artificial intelligence-powered software
to visually search a mouth swab sample for signs of the novel coronavirus.
A deep mutational scanning method maps how all amino-acid mutations
in the SARS-CoV-2 spike receptor-binding domain affect antibody binding.
These complete maps enable designing escape-resistant antibody cocktails.
https://www.biorxiv.org/content/10.1101/2020.09.10.292078v1
Florida reportedly withholding school COVID-19 case data
Duval County Department of Health said the school system cannot publish
"school-specific data related to COVID-19" without the state health department's permission.
"In the interest of public health in Florida, the Surgeon General
instructed county health departments to provide school districts
with information regarding COVID-19 cases in their schools,"
Volusia County Department of Health spokeswoman Holly Smith stated in an email.
"However, this information is considered confidential."
synthetic biology research "biofoundry" robotic technology repurposed for COVID-19 testing
Each machine has the capacity to process up to 1000 samples within 12 hours.
https://www.nature.com/articles/s41467-020-18130-3
Computer-designed small protein LCB1 rivals the best-known
SARS-CoV-2 neutralizing antibodies in its protective actions. Beginning in January,
more than two million candidate Spike-binding proteins were designed on computers.
Over 118,000 were then produced and lab tested.
"hyperstable minibinders provide promising starting points for new SARS-CoV-2 therapeutics"
AKA picomolar SARS-CoV-2 miniprotein inhibitors
https://science.sciencemag.org/content/early/2020/09/08/science.abd9909
Interaction network of SARS-CoV-2 with host receptome through spike protein
Other than ACE2, little is known about SARS-CoV-2 receptors.
This research identified 12 receptors, including ACE2 , using genomic receptor profiling.
https://www.biorxiv.org/content/10.1101/2020.09.09.287508v2
A high-cell-density protocol using DXB11-derived CHOBRI/rcTA cells
gave substantially better yields than the other methods
for rapid production of full-length SARS-CoV-2 spikes,
including the wild-type SARS-CoV-2 sequence and a mutated/stabilized form.
These are important for diagnostic and therapeutic research and development.
https://www.biorxiv.org/content/10.1101/2020.09.08.286732v1
32% of people in the U.S. are overweight. Compared to those with healthy weights,
obese COVID-19 patients are more likely to be to be hospitalized (113%), admitted to ICU (74%) and die (48%).
Even after accounting for other risk factors associated with obesity, including
impaired immunity, chronic inflammation, blood that's prone to clot, heart disease,
lung disease, diabetes and metabolic syndrome, body mass index remains a strong independent risk factor.
A transverse myelitis case pauses AstraZeneca's AZD1222 coronavirus vaccine trial.
"When you are inoculating 20,000 people,
it is a foregone conclusion that at some point you will have severe adverse events.
As soon as a link to the vaccine can clearly be ruled out, the trial continues"
AZD1222 uses an adenovirus to convey SARS-CoV-2 antibody genetic instruction, an
approach also used by China's CanSino, Russia's Gamaleya institute and Johnson & Johnson.
https://www.reuters.com/article/us-health-coronavirus-astrazeneca-idUSKBN26017L
Efficient replication of SARS-CoV-2 relies on the activity of nonstructural protein 1 (Nsp1),
a major virulence factor shown to facilitate suppression of host gene expression
through promotion of host mRNA degradation and interaction with the 40S ribosomal subunit.
Here is reported the crystal structure of the globular domain of SARS-CoV-2 Nsp1.
https://www.biorxiv.org/content/10.1101/2020.09.08.288191v1
BromAc (Bromelain & Acetylcysteine) has been described
to disrupt glycoproteins by the synchronous breakage of glycosidic linkages and disulphide bonds.
This in vitro study shows recombinant spike and envelope SARS-CoV-2 protein fragmented by BromAc.
https://www.biorxiv.org/content/10.1101/2020.09.07.286906v1
LabCorp announced plans to launch a new at-home COVID-19 diagnostic that allows
people to also test for the flu and respiratory syncytial virus from a single sample.
The combined test is currently offered through doctors' offices, hospitals
and other healthcare providers, while the future, home-based version will be
made available through LabCorp's Pixel service, pending FDA review and authorization.
A new test manufactured by A*STAR's Diagnostics Development Hub
in partnership with Duke-NUS Medical School
could reveal if an individual is likely immune to COVID-19.
https://medicalxpress.com/news/2020-09-antibodies.html
Substantial underestimation of SARS-CoV-2 infection in the U.S.
Semi-Bayesian probabilistic bias analysis estimates 6,454,951 cumulative infections
compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the U.S. as of April 18, 2020.
Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher
than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference
is due to incomplete testing, while 14% (0.3-36%) is due to imperfect test accuracy.
https://www.nature.com/articles/s41467-020-18272-4
Data from the study of SARS-CoV and other respiratory viruses suggest that
anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE).
Clinical data has not yet fully established a role for ADE in human COVID-19 pathology.
This paper discusses ADE mechanisms, mitigation strategies and recently published data.
https://www.nature.com/articles/s41564-020-00789-5
The SARS-CoV-2 coding capacity map was previously based on computational predictions
and relies on homology to other coronaviruses. Here, ribosome profiling techniques
produce a high-resolution map of SARS-CoV-2 coding regions,
accurately quantifying expression of canonical viral open reading frames (ORFs)
and identifying 23 unannotated viral ORFs.
https://www.nature.com/articles/s41586-020-2739-1
9 errors of intuition that still hamstring the U.S. pandemic response [5000 words]
1. A Serial Monogamy of Solutions 2. False Dichotomies 3. The Comfort of Theatricality
4. Personal Blame Over Systemic Fixes 5. The Normality Trap 6. Magical Thinking
7. The Complacency of Inexperience 8. A Reactive Rut 9. The Habituation of Horror
low-cost chip detects presence and quantity of COVID-19 antibodies
Opto-microfluidic sensing platform based on localized surface plasmon resonance
involving gold nanospikes (fabricated by electrodeposition) in a microfluidic device,
coupled with an optical probe.
https://www.sciencedirect.com/science/article/pii/S0956566320305686
Since masks can filter out some virus-containing droplets (with filtering capacity
determined by mask type), masking might reduce inoculum inhaled.
If this theory bears out, population-wide masking,
with any type of mask that increases acceptability and adherence, might contribute to
increasing the proportion of SARS-CoV-2 infections that are asymptomatic.
https://www.nejm.org/doi/full/10.1056/NEJMp2026913
The coronavirus is mutating - does it matter?
[ as seems nearly always the case, this article avoids answering its title question ]
Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads.
Despite its sluggish mutation rate, researchers have catalogued more than 12,000 mutations
in SARS-CoV-2 genomes, but they spot mutations faster than make sense of them.
The D614G mutation reportedly represents a "more transmissible form of SARS-CoV-2".
No one has yet found any change in SARS-CoV-2 that should raise public-health concerns.
However, G viruses tended to transmit 20% faster
than lineages that didn't carry the change, and formed larger clusters of infections.
https://www.nature.com/articles/d41586-020-02544-6
Operation Warp Speed: interim report card
On its site, OWS lists the development and testing of diagnostics as one of its five focus areas.
In reality, OWS appears to have stayed largely on the sidelines, with the NIH taking the lead.
When it comes to OWS plans to distribute vaccines when they become available,
the initiative has not been forthcoming.
McKesson, one of the three largest pharmaceuticals wholesalers in the U.S.,
has been contracted to be a central distributor of vaccines.
McKesson plays this same role in the annual distribution of influenza vaccines,
but its role here has not been clearly defined.
FDA officials are still allowed to interact with companies developing products for OWS,
but barred from sitting in on OWS focuses, like procurement, investment or distribution.
9 vaccine makers sign safety pledge in race for COVID-19 vaccine
[ credibility of Trump, FDA and CDC vs big pharma ]
"We, the undersigned biopharmaceutical companies, want to make clear
our on-going commitment to developing and testing potential vaccines for COVID-19
in accordance with high ethical standards and sound scientific principles."
The companies that signed the pledge include AstraZeneca, BioNTech, Moderna,
Pfizer, Novavax, Sanofi, GlaxoSmithKline, Johnson & Johnson and Merck.
Mask mandates delayed by nearly a month in Republican-led states.
Currently, 14 states do not have any statewide mask mandate;
3 states have a limited requirement for masks in some settings.
https://www.medrxiv.org/content/10.1101/2020.08.31.20185371v1
A study shows no statistically significant differences in the rates of hospitalization,
ICU admission and mechanical ventilator use between children with COVID-19
and those with seasonal influenza A and B. "It took several rounds
of thinking and combing through the data to convince myself that this was the conclusion."
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770250
While older people and people with underlying medical conditions
produce greater quantities of an important type of immune cell known as "T-helper cells,"
their T-helper cells show impaired function.
One substance known to act as a molecular 'brake' on the immune system is the protein PD-1.
This 'molecular brake' on the immune system could serve
as a potential new treatment target in patients with severe COVID-19.
https://www.jci.org/articles/view/140965
Hospitals have a choice: treat COVID-19 patients under the convalescent plasma EUA
or enroll them in clinical trials that will help establish another treatment's safety and efficacy.
In severely affected patients, SARS-CoV-2 triggers chronic immune reactions
which are controlled by TGF-B, with most of the activated B cells
being no longer specific for the SARS-CoV-2 spike protein
and its receptor binding domain, nor for nucleoprotein.
TGF-B may be a candidate target to ameliorate detrimental immunopathology in those patients.
https://www.medrxiv.org/content/10.1101/2020.09.04.20188169v1
With a time-adjusted dataset of epidemiological statistics for national
and subnational jurisdictions at the time point of 6 months after the first exposure,
statistical significance of the correlation hypothesis between
the record of universal BCG vaccine immunization performed at birth or early infancy
and milder COVID-19 epidemiological scenario is convincing.
https://www.medrxiv.org/content/10.1101/2020.09.06.20189423v1
Studies of asymptomatic COVID-19 patients revealed more than half had lung abnormalities.
A March study published in the Journal of the American Heart Association found that
7 to 20% of sick patients showed heart damage associated with COVID-19.
"if a man in his 30s and a man in his 60s both contract COVID-19,
it is more likely that the 30-something will develop a months-long illness
than that the 60-something will die"
https://www.theatlantic.com/ideas/archive/2020/09/what-young-healthy-people-have-fear-covid-19/616087/
Much SARS-CoV-2 antibody research has concentrated on specific sites in its Spike protein.
This paper investigates antibody responses to full-length S protein.
https://www.nature.com/articles/s41423-020-00523-5
Nitazoxanide (NTZ) is a safe and approved molecule effective against helminths
and numerous microorganisms, including bacteria and viruses. In vivo,
NTZ is metabolized into Tizoxanide (TIZ), which is the active circulating metabolite,
with clinical trials for its effectiveness against SARS-Cov-2.
This research highlights fatty acid synthase (FASN) inhibition
to explain the wide antiviral action of this substance, without determining a specific mechanism.
https://www.nature.com/articles/s41598-020-71634-2
This large observational population study shows a strong association between vitamin D
deficiency and COVID-19 occurrence. After adjustment for baseline characteristics and prior
vitamin D levels, acquisition of liquid vitamin D formulations
is associated with decreased risk for COVID-19 infection.
https://www.medrxiv.org/content/10.1101/2020.09.04.20188268v1
pandemic Summer and Fall
While South Carolina's short-term rentals were about 72% booked for July,
the occupancy rate on Hilton Head was 90.1%, about the same as in July 2019.
July's occupancy rate for island rentals through services such as
Airbnb and VRBO was 22% above the national average.
Airbnb listed Hilton Head as one of its top destinations for Labor Day weekend.
Hilton Head's hotels also had higher occupancy than hotels in other parts of South Carolina,
but were off around 30% from last summer.
On Labor Day weekend, The Marriott Hilton Head Resort & Spa,
the Westin Hilton Head Island Resort & Spa and the Omni Hilton Head Oceanfront Resort
were all sold out for Saturday arrivals.
https://www.islandpacket.com/news/coronavirus/article245491660.html
More than 50,000 cases have been confirmed on college campuses since the pandemic began,
leading to last-minute instructional changes and sudden disciplinary actions,
including suspensions and dismissals without tuition reimbursement.
Many aren't conducting robust testing of students; in fact,
the CDC didn't recommend testing when some colleges opened for summer instruction.
https://www.vox.com/2020/9/5/21424311/colleges-suspensions-dismissal-coronavirus-students
Clinical and economic value of different COVID-19 mitigation strategies on college campuses
estimated by the Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model:
per 5000 students (1000 faculty) over 1 semester from 3,746 (164) cases with no mitigation:
493 (28) with extensive social distancing (ESD) and masks
151 (25) by adding routine laboratory tests among asymptomatic students and faculty
No strategies without masks were cost-effective.
Extensive social distancing with mandatory mask-wearing
could very cost-effectively prevent 87% of COVID-19 cases on college campuses.
Routine laboratory testing would prevent 96% of infections
but require low cost tests to be economically attractive.
https://www.medrxiv.org/content/10.1101/2020.09.03.20187062v1
Long, thin transmission chains of SARS-CoV-2) may go undetected for weeks
Wherever surveillance systems are weak and/or
younger age groups with lower rates of overt symptoms dominate transmission,
contact tracing and isolation effectiveness may be more severely limited,
even at the higher reproduction numbers associated with larger outbreaks.
https://www.medrxiv.org/content/10.1101/2020.09.04.20187948v1
Estimating COVID-19 hospital demand using a non-parametric model
Standard methods, like the Kaplan-Meier estimator,
require prior assumptions that are untenable given current knowledge.
A nonparametric Mixture Cure Model outperformed standard approaches,
providing more accurate ICU and hospital ward length-of-stay estimates.
Adjusting for sex, generally overlooked in prediction models,
together with age is key for accurately forecasting ICU occupancy.
https://www.medrxiv.org/content/10.1101/2020.09.04.20187963v1
Two types of unconventional T cells, mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT),
were dramatically reduced in the blood of patients with severe COVID-19.
However, the number of MAIT cells increased in the patients' airways, suggesting that
these cells might move from the blood to the lungs to control the response to SARS-CoV-2 infection.
https://medicalxpress.com/news/2020-09-unconventional-cells-severe-covid-patients.html
It has been thought that a cytokine storm contributes to disease severity in patients with COVID-19.
Following the measurement of several important cytokines in patients with COVID-19 and various other severe diseases,
researchers at Radboud university medical center now show that COVID-19 is not characterized by a cytokine storm.
"The level of cytokines was significantly less elevated in COVID-19 patients
than in patients with septic shock and ARDS. Compared to patients with septic shock without ARDS,
so without severe pulmonary disease, patients with COVID-19 also displayed markedly lower levels of IL-6 and IL-8.
The cytokine concentrations in COVID-19 patients were similar to those in IC patients with trauma or cardiac arrest,
conditions that are not noted for a cytokine storm."
https://medicalxpress.com/news/2020-09-covid-cytokine-storm.html
A group at the Snyder Institute for Chronic Diseases at the Cumming School of Medicine
is the first in the world to find a way to record, in real time,
how the immune system battles bacteria impacting the alveoli, or air sacs, in the lungs of mice.
The ability to see macrophages at work has revealed something else: the scientists watched
as the powerful cleaners became paralyzed and stopped doing their important job.
"The next step in our research is
to find out why this is happening so that we can develop targeted therapies
to kickstart the macrophages into action again"
Broad, and frequently strong, SARS-CoV-2-specific CD4+ and CD8+ T cell responses
were seen in the majority of convalescent COVID-19 patients,
with significantly larger overall T cell responses in those who had severe compared with mild disease.
However, there was a greater proportion of CD8+ T cell compared with CD4+ T cell responses in mild cases,
with higher frequencies of multi-cytokine production by matrix (M)- and NP-specific CD8+ T cells.
https://www.nature.com/articles/s41590-020-0782-6
Almost all of the current vaccines in the human immunization programme are delivered via the skin or muscle,
and most of the current COVID-19 vaccine strategies also focus on the parenteral route of vaccination.
A respiratory mucosal vaccine strategy capable of inducing these responses
directly in the respiratory mucosa will be most effective in the early control or clearance of SARS-CoV-2.
https://www.nature.com/articles/s41577-020-00434-6
The coronavirus main protease (Mpro, also called 3CLpro) is essential for processing
and maturation of the viral polyprotein, therefore recognized as an attractive drug target.
A clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor
against feline infectious peritonitis (corona) virus (FIPV), GC376,
both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting Mpro.
Moreover, combined application of GC376 with Remdesivir,
a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp),
results in sterilizing additive effect.
https://www.nature.com/articles/s41467-020-18233-x
ribosome binding pocket may be a target for drugs to treat COVID-19
Once inside host cells, not only does SARS-CoV-2 hijack cells' translational machinery
to make viral proteins, but the virulence factor nonstructural protein 1 (Nsp1)
also shuts down translation of host messenger RNA,
almost completely inhibiting the innate immune response.
https://science.sciencemag.org/content/369/6508/1249
Systems biological assessment of immunity to mild versus severe COVID-19 infection
SARS-CoV-2 infection results in a spatial dichotomy in the innate immune response,
characterized by suppression of peripheral innate immunity
in the face of proinflammatory responses that have been reported in the lungs. Additionally,
cytokine response shifts from transient type I interferon response early in infections
to proinflammatory response during later and more severe stages.
https://science.sciencemag.org/content/369/6508/1210
70% of new U.S. COVID-19 cases are in Republican-led states
14 states have been listed as "red zones" since June 23
as places such as Arizona, Florida, Georgia, Oklahoma, South Carolina and Tennessee
fail to impose mandatory mask mandates to curb the virus's spread.
Pentagon Picks 5 military hospitals for AstraZeneca phase 3 trial sites.
State University of New York at Oneonta plans to send on-campus students home and
cease all in-person classes for the rest of the fall semester after a COVID-19 outbreak.
Fauci warns Midwestern states in particular to be vigilant during the Labor Day holiday.
"There are several states that are at risk for surging,
namely North Dakota, South Dakota, Iowa, Arkansas, Missouri, Indiana, Illinois"
Interview with Moncef Saloui, scientific head of Operation Warp Speed
[ General Gustave Perna is Operation Warp Speed chief operating officer ]
"Our intent is to drive the companies to a BLA
[Biologics License Application, FDA's full approval process for a vaccine]
that should be filed 1, 2, 3 months from an emergency use designation."
CoroNAb consortium's alpaca nanobody may prevent COVID-19 infection.
"Our results show that Ty1 can bind potently to the SARS-CoV-2 spike protein
and neutralize the virus, with no detectable off-target activity.
We are now embarking on preclinical animal studies
to investigate the neutralizing activity and therapeutic potential of Ty1 in vivo."
https://www.nature.com/articles/s41467-020-18174-5
Massachusetts General Hospital reports blood type unrelated to COVID-19 severity,
but symptomatic Rh+, type B and AB patients test positive more often than do type O.
"This evidence should help put to rest previous reports of a possible association
between blood type A and a higher risk for COVID-19 infection and mortality."
https://link.springer.com/article/10.1007/s00277-020-04169-1
Jena authorities were the first in Germany to introduce universal community-wide masking,
i.e. mandatory covering of the mouth and nose in public buildings
and public transport accepting also cloth masks or scarfs.
There were no new COIVD-19 cases in Jena five days after implementation,
which is in line with the average incubation time of SARS-CoV-2. In Erfurt, COVID-19
continued spreading and only ceased after the same community-wide masking was imposed.
https://www.medrxiv.org/content/10.1101/2020.09.02.20187021v1.full.pdf+html
Phase 1-2 trial of Novavax NVX-CoV2373 COVID-19
recombinant spike protein nanoparticle vaccine candidate:
At 35 days, NVX-CoV2373 appeared to be safe,
and it elicited immune responses that exceeded levels in COVID-19 convalescent serum.
https://www.nejm.org/doi/full/10.1056/NEJMoa2026920
FDA EUA for Roche fully automated test to detect and differentiate
SARS-CoV-2, influenza A virus and/or influenza B virus with a single sample.
The systems provide up to 96 results in about 3 hours
and 384 results for the cobas 6800 System
and 1,056 results for the cobas 8800 System in an 8-hour shift.
https://www.roche.com/media/releases/med-cor-2020-09-04.htm
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.
The median incubation period of the disease is 4 days,
and the longest is no more than 41 days. The patient at incubation period is contagious,
and the median duration of viral shedding was 20 days in survivors,
but SARS-CoV-2 was detectable until death in non-survivors.
The longest observed duration of viral shedding in survivors was 37 days.
https://www.nature.com/articles/s41467-020-18233-x
This study used a structure-based approach of the SARS-CoV-2 Spike protein,
taking into account the glycan chains, with the objective of identify B-cell epitopes
unshielded by glycosylation. A complete trimeric 3D model of the S-protein was first built
and used as a base on which several glycosylated models were generated.
22 experimentally determined N-glycosylation sites were evaluated
to differentiate SARS-CoV-2 S-protein antigenic regions exposed to B cells
from epitopes shielded by a glycan chain. 28 protruding epitopes were identified,
and their accessibility was evaluated based on position and glycan shielding
and categorised into three groups based on the degree of accessibility lost upon glycosylation.
https://www.nature.com/articles/s41541-020-00237-9
Evolution of the COVID-19 vaccine development landscape
The majority of vaccine candidates currently in clinical trials target the spike (S) protein
and its variants as the primary antigen.
https://www.nature.com/articles/d41573-020-00151-8
Sterol regulatory element binding protein-2
can serve as an indicator for COVID-19 severity diagnosis
and therapeutic target for preventing cytokine storm and lung damage.
https://www.nature.com/articles/s41392-020-00292-7
CDC's Redfield mailed governors of all 50 states to prepare for a vaccine as early as October,
with health care workers and long-term facility residents among the first to receive the vaccine.
Redfield requested governors to waive any regulatory barriers that would prevent McKesson
from having distribution facilities operational by Nov. 1.
Plan technical specifications for two candidates described as Vaccine A and Vaccine B,
including requirements for shipping, mixing, storage and administration,
seem to match the products developed by Pfizer and Moderna,
which are the furthest along in late-stage clinical trials. On Aug. 20,
Pfizer said it was "on track" for seeking government review "as early as October 2020."
[ note: Moderna is still soliciting volunteers for their trial, so not many results by Nov. ]
A new system, which has already been used to detect a protein linked to cystic fibrosis,
can compile a detectable COVID-19 signal from just a few biomarkers in a few minutes.
Conventional detection requires collecting billions of biomarkers.
"By coupling DNA origami and nanopores
we are able to quantitatively detect disease biomarkers with single molecule sensitivity."
https://www.nature.com/articles/s41467-020-18132-1
A new vaccine development involves altering specific sequences of messenger RNA,
known as untranslated regions (UTRs). "For our application we tried to optimize the UTRs
to improve the protein production process. We wanted as much protein produced as possible
- so we can give a small dose of messenger RNA that produces enough antigen
to induce antibodies against the virus"
https://onlinelibrary.wiley.com/doi/full/10.1002/adma.202004452
Children can have COVID-19 antibodies and virus in their system simultaneously.
"With most viruses, when you start to detect antibodies, you won't detect the virus anymore.
But with COVID-19, we're seeing both"
https://www.jpeds.com/article/S0022-3476(20)31114-8/fulltext
Of 91 children with confirmed COVID-19, 20 children (22%) who were asymptomatic
for the entire observation period. Of symptomatic cases,
66% had unrecognized symptoms before diagnosis,
25% developed symptoms after diagnosis, and
9% were diagnosed at the time of symptom onset
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2770150
COVID-19 patients should be swab tested again 4 or more weeks after symptoms first appear
to minimise the risk of onward infection. SARS-CoV-2 takes an average of
30 days to clear from the body after the first positive test result and
36 days after symptoms first appear, dnd it's not yet known
how infectious patients may be during recovery.
https://medicalxpress.com/news/2020-09-retest-covid-weeks-symptoms-curb.html
Australian scientists using cloud-based supercomputer programs
have joined forces with biotechnology company Vaxine Pty Ltd
to identify up to 80 new potential candidate drugs against the COVID-19 virus.
Top candidates include a substantial number of drugs
and natural products not previously identified as having potential COVID-19 activity.
https://arxiv.org/abs/2009.00744
A computer model can for the first time estimate the combined health and wealth outcomes
of different policy responses to the coronavirus pandemic. "There is a huge difference
between what the same policy can do in Sacramento and what it can do in Chicago"
https://reopenmappingproject.com/
A new report from life science data analytics firm GlobalData has found that
two-thirds of healthcare experts surveyed over the summer
plan to use decentralized clinical trials. Out of 150 survey respondents,
only 34% were already using decentralized clinical trials,
with most located in North America.
Your state's COVID-19 epidemic in 5 maps
33 states report more than 60% ICU beds occupied Sept 2.
27 states have more than 5% positive test results
24 states have high infection spread rates
Only 6 states have fewer than 4 new daily cases per 100k
Broad serum antibody responses against peptides of seasonal hCoVs are detected
in up to 75% of individuals. Up to 50% of recovered patients
also mounted antibody responses against unique epitopes of seasonal hCoV-OC43,
that were not detectable in unexposed individuals.
https://www.medrxiv.org/content/10.1101/2020.09.01.20182220v1
Bayesian model comparison found overwhelming evidence
for heterogeneity of exposure, susceptibility, and transmission.
Small variations in heterogeneity were sufficient
to explain the large differences in mortality rates across countries. A dynamic causal model
that incorporates heterogeneity of exposure, susceptibility and transmission suggests that
the next wave of the SARS-CoV-2 pandemic will be much smaller than conventional models predict,
with less economic and health disruption. This heterogeneity means that
seroprevalence underestimates effective herd immunity and, crucially,
the potential of public health programmes.
https://www.medrxiv.org/content/10.1101/2020.09.01.20185876v1
Ben-Gurion University of the Negev (BGU) data scientist Prof. Mark Last
sees the end of the coronavirus peak in Israel and believes that
New York and California may have reached herd immunity.
[ This definition of herd immunity is based on infection rate R0 < 1,
which currently depends on social distancing as much as personal immunities. ]
https://medicalxpress.com/news/2020-09-york-california-herd-immunity-scientist.html
Humoral Immune Response to SARS-CoV-2 in Iceland
[ Humoral immunity or humoural immunity is the aspect of immunity
that is mediated by macromolecules found in fluids outside cells, such as
secreted antibodies, complement proteins, and certain antimicrobial peptides. ]
Based on antibodies in serum samples from 30,576 persons in Iceland,
antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis,
the risk of death from infection was 0.3% and
44% of persons infected with SARS-CoV-2 were not diagnosed by qPCR.
https://www.nejm.org/doi/full/10.1056/NEJMoa2026116
Diagnostic devices that are used at home or in doctors' offices are often not sensitive enough
to detect small amounts of a virus that might be present in samples from asymptomatic patients,
which can occur in early stage COVID-19.
A membrane-based invention concentrates virus content of samples, allowing detection.
https://aip.scitation.org/doi/10.1063/5.0013987
Florida severs COVID-19 testing relationships with Quest
Late on August 31, 2020, the Governor's office was informed that nearly 75,000
of approximately 1.4 million COVID-19 tests Quest had performed and reported,
dating as far back as April, were to be entered into FL DOH COVID-19 monitoring system.
While data, for the most part, were over 2 weeks old - with some being almost 5 months old -
the state incorporated information that would be useful and included the rest
in the interest of transparency. Per Quest, all individuals that tested positive were notified of their results.
https://newsroom.questdiagnostics.com/COVIDTestingUpdates
Expansion of atypical memory B cells is a prominent feature of COVID-19
[ B cells are one of the two types of lymphocytes (the others being T cells).
All lymphocytes begin their development in the bone marrow;
those that migrate to the thymus mature into T cells.
B cells are involved in so-called humoral immunity. ]
The proportion of atypical memory B cells was significantly higher
in COVID-19 patients who died than in those who survived.
https://www.nature.com/articles/s41423-020-00542-2
SARS-CoV-2-specific T cells are present even in seronegative convalescent patients,
with T cells but not antibodies still detectable 109 days post infection.
https://www.nature.com/articles/s41577-020-00441-7
Nanobodies have unique biophysical properties,
including small size and thermostability, that allow aerosolized administration.
Nb11-59, the candidate with highest neutralizing activity was selected from 381 nanobodies
produced by camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD).
Production of Nb11-59 in a yeast expression system followed by its nebulization
showed potential for rapid and high-quality manufacturing.
https://www.biorxiv.org/content/10.1101/2020.08.09.242867v2
In the ACTIVATE study, 198 patients over 65 years of age who were admitted to hospital
2 years ago were randomized to receive BCG or placebo vaccination at their discharge.
In the placebo group, 42.3% of the elderly developed an infection,
while this was the case in only 25% of BCG-vaccinated participants
who had their first infection on average 16 weeks after vaccination,
compared to 11 weeks for the placebo group. There was no difference in side effects.
"BCG-vaccinated elderly people had 75% fewer respiratory infections
than the elderly who received placebo."
https://www.cell.com/cell/pdf/S0092-8674(20)31139-9.pdf
7-day rolling average of daily new reported cases per 100K by state
MO: 21 (+21%), GA: 20 (-15%), SC: 19 (+11%), TX: 17 (-11%), KY: 14 (+5%), FL: 14 (-19%),
CA: 13 (-12%), VA: 12 (+10%), AZ: 7 (-21%), WA: 6 (-11%), CO: 5 (-4%), NY: 3 (+10%)
Localities reported not only a surge in new cases but also large increases
in hospitalizations, crowded ICUs, and a jump in the percentage of positive tests.
COVID-19 and interferons
Interferons are immune proteins that normally interfere with virus' life cycles.
In addition to their antiviral properties, they summon natural killer cells,
"the best soldiers, as it were, of the innate immune system," said Fauci.
This paper documents that SARS-CoV-2 reduces and delays interferon production,
and found that higher inteferon concentrations during ICU entry were associated with
lower SARS-CoV2 viral load in the respiratory tract and faster viral clearance:
https://www.medrxiv.org/content/medrxiv/early/2020/08/24/2020.08.21.20179291.full.pdf
The NIH is evaluating interferon boosts, but so far only for ventilated ICU patients
https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/
Bolder BioTechnology announced positive preclinical data for inhibiting SARS-CoV-2
by use of their
BBT-032 proprietary long-acting interferon beta analog,
developed for treating Multiple Sclerosis and other inflammatory diseases.
An NIH-sponsored clinical trial launched this month will inject 1,000 patients with interferon beta-1a,
a synthetic molecule used to treat multiple sclerosis and identical to a protein our bodies make,
every other day for the first week of their hospital stay.
Trial patients will be sick but not so ill as to require ventilators to breathe.
https://clinicaltrials.gov/ct2/show/NCT04492475
By analyzing disparate pandemic strategies and results among all 3,142 U.S. counties
and the District of Columbia, Duke researchers found that only the most aggressive
control measures, such as stay-at-home orders and mask mandates,
produced across-the-board reductions in both COVID-19 cases and deaths.
Closing businesses and limiting social gathering sizes reduced cases and deaths
in some parts of the country, but not others.
https://www.medrxiv.org/content/10.1101/2020.08.18.20177600v1
Partnership deals for COVID-19 diagnostics and therapies
Diagnostic tests presently used fall largely into two groups:
those that detect viral nucleic acid sequences and
those that detect antibodies to SARS-CoV-2 produced by the immune system.
Nucleic acid-based tests are simpler to develop and more accurate,
but only for active infections.
https://www.nature.com/articles/d43747-020-01115-y
Severe COVID-19 despite or even due to strong immunity
"The total number of specific immune cells as well as their functionality
was not better in patients who survived COVID-19 than in those who died from it"
"...our data suggest that excessive SARS-Cov-2-specific T cell response
can cause immunopathogenesis leading to COVID-19-related lung failure."
"The results of current studies on the successful application of immunosuppressive therapies
in COVID-19 support this hypothesis."
https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(20)30118-X.pdf
National Academies of Sciences, Engineering, and Medicine expect 4 of 7 COVID-19 vaccines to fail
"Four of the trials will fail, and all subjects in those trials are
offered access to an approved vaccine," the group wrote in their draft
report. "Three of the trials will succeed, and,
under a 1:1 ratio between members of treatment groups compared to the
placebo group,
15,000 participants from each of those trials
who were assigned to the placebo condition are offered an approved vaccine."
Vaccines would then be distributed in four phases with health-care
workers and vulnerable Americans, such as the elderly and those with
underlying health conditions, getting it first.
The U.S., as part of Operation Warp Speed, has already invested billions of dollars
in 6 potential vaccines, including from drug companies Pfizer, Moderna and AstraZeneca,
which have entered phase 3 trials.
The public comment period is open from noon EDT Tuesday, Sept. 1, until 11:59 p.m. EDT Friday, Sept. 4.
Equitable Allocation of COVID-19 Vaccine: Public Listening Session
The study committee will host a public listening session on Wednesday,
September 2,
from 12:00 to 5:00 p.m. ET. During this session,
members of the public will have an opportunity to address the committee directly
(as individuals or representatives of organizations).
Registration for the public listening session is now open,
and members of the public can sign up to speak.
America Is Facing a Monkey Shortage
Monkeys account for just 0.5% of the animals used in U.S. biomedical research,
but they typically represent the last step before human clinical trials.
The NIH is now centrally deciding which studies can use the national primate centers.
https://www.theatlantic.com/science/archive/2020/08/america-facing-monkey-shortage/615799/
EUA might get Novavax's COVID-19 vaccine to market first
Novavax phase 2 trial started a month after Moderna, AstraZeneca and Pfizer, but:
an EUA may be granted based on strongly positive phase 2 data from a smaller sample
than larger trials with less compelling results.
* Novavax NVX-CoV2373 phase 1 data was so positive that some consider it best in class,
and a 2,665-volunteer phase 2 study is already running in South Africa.
Its candidate works in traditional ways and can be stored in a refrigerator.
The company has experience with other virus outbreaks like Ebola and SARS,
with vaccines for both in its pipeline.
* In AstraZeneca's animal trials, all vaccinated monkeys became infected when challenged.
* Moderna and Pfizer mRNA vaccines must be stored at negative 80 degrees Celsius.
Its lopinavir and ritonavir combination having failed across the board in a recent clinical trial
with 199 COVID-19 patients, AbbVie teamed with Harbour BioMed, Utrecht University
and Erasmus Medical Center and will now provide to Harvard Medical School $30 million
over three years and additional, in-kind support leveraging AbbVie's scientists, expertise
and facilities to advance collaborative research and early-stage development efforts
across five program areas related to SARS-CoV-2.
Authorized in May only for patients with severe coronavirus who needed help breathing,
clinical trials showed a five-day course could reduce recovery time in moderately ill patients.
University of Washington's Institute for Health Metrics and Evaluation (IHME) model projects
more than 300,000 U.S. COVID-19 deaths by year end.
"if mask wearing in public increases to 95%, more than 67,000 lives could be saved."
http://www.healthdata.org/covid/updates
A 25-year-old resident of Reno, Nevada was infected with SARS-CoV-2, 2 times,
about 48-days apart, with the second infection causing a more severe case of COVID-19
than the first and requiring hospitalization and oxygen support.
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3681489
Structural basis of a shared antibody response to SARS-CoV-2
The immunoglobulin heavy-chain variable region 3-53 gene is the most frequently used
among 294 antibodies that target the receptor-binding domain (RBD) of the viral spike protein.
To understand why IGHV3-53 is elicited as a shared antibody response, molecular interactions
between the RBD and heavy chains of CC12.1, CC12.3, and B38 were analyzed.
None of these antibody interactions mimics ACE2 binding.
https://science.sciencemag.org/content/369/6507/1119
The Royal Pharmaceutical Society has made
this feature article free to access
in order to help healthcare professionals stay informed about an issue of national importance.
Saliva specimens and nasopharyngeal swab specimens had similar sensitivity
in the detection of SARS-CoV-2 RNA in both symptomatic and asymptomatic persons.
https://www.nejm.org/doi/full/10.1056/NEJMc2016359
University of Alberta researchers prepare a COVID-19 clinical trial using antiviral for cats.
First studied by U of A chemist John Vederas and biochemist Michael James following the 2003 outbreak
of severe acute respiratory syndrome (SARS), the protease inhibitor was further developed
by veterinary researchers who showed it cures a disease that is fatal in cats.
https://www.nature.com/articles/s41467-020-18096-2
Rigorous SARS-CoV-2 testing and infection-control measures prevented outbreaks
at four overnight camps in Maine that hosted hundreds of children between mid-June and mid-August.
Of more than 1,000 attendees, 2 staff members and one camper tested positive at camp
and were isolated until they tested negative. The 30 people in the camper's cohort were quarantined;
all tested negative for the virus during quarantine. Authors say that
the virus did not spread beyond the three infected attendees.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6935e1.htm?s_cid=mm6935e1_w
A study from the Brown School at Washington University in St. Louis
provides the first explicit analysis of the timing, determinants
and impacts of mitigation interventions for all states and Washington, D.C.
Of 9 mitigation measures, 3 (non-essential business closure, large-gathering bans
and restaurant/bar limitations) showed positive impacts on reducing cumulative cases,
new cases and death rates across states.
https://www.medrxiv.org/content/10.1101/2020.05.29.20117259v1
Severe COVID-19: It felt like dying in solitary confinement
One day I was a healthy 44-year-old doctor, CEO of a health care company,
and a triathlete who was prepared to do another triathlon.
Then I was a COVID-19 patient a few shallow breaths away from being put on a ventilator.
A nurse saved me from that fate.
https://www.statnews.com/2020/08/28/my-severe-covid-19-felt-like-dying-in-solitary-confinement/
U.S. COVID-19 cases is back over 40K. Before the hurricanes,
Mississippi's seven-day average positivity test rate was 27.4%, the highest in the nation.
Using the National Drug Discovery Center, researchers from the Walter and Eliza Hall Institute
identified drug-like compounds that could block a protein, PLpro, found in all coronaviruses
and essential for them to hijack and multiply within human cells, disabling their anti-viral defenses.
Initially developed as potential treatments for SARS,
the compounds prevent SARS-CoV-2 growth in the laboratory.
https://www.embopress.org/doi/full/10.15252/embj.2020106275
Having received a $42 million contract from the Canadian government earlier this month
to support its COVID-19 vaccine development program through phase 2 testing,
Massachusetts-based VBI Vaccines has selected COVID-19 vaccine candidates VBI-2901 and VBI-2902
for development and expects to launch human clinical testing by the end of the year.
https://www.vbivaccines.com/wire/preclinical-coronavirus-data-candidate-selection/
A panel of human neutralizing mAbs targeting SARS-CoV-2 at 4 epitopes on the spike RBD
Neutralization potency of the antibodies was evaluated by
plaque reduction neutralization test (PRNT) using infected VeroE6 cells.
Antibodies MD45, MD67, MD62, and MD65 displayed highest neutralization potencies.
https://www.nature.com/articles/s41467-020-18159-4
"Weather probably influences COVID-19 transmission,
but not at a scale sufficient to outweigh the effects of lockdowns or re-openings in populations"
All pharmaceutical and non-pharmaceutical interventions are currently believed
to have a stronger impact on transmission over space and time than any environmental driver.
https://www.nature.com/articles/s41467-020-18150-z
Replacing water in dental equipment with FDA-approved polymer solutions
can mitigate spray droplets and aerosols generated during dental procedures.
https://aip.scitation.org/doi/10.1063/5.0021476
Detailed dataset of measures to curb COVID-19 ready for statistical analyses.
Started in March, the Complexity Science Hub Vienna (CSH) comprehensive worldwide collection
of governmental measures is now published in the Nature journal Scientific Data.
https://www.nature.com/articles/s41597-020-00609-9
How to use ventilation and air filtration to prevent COVID-19 indoor spread.
Two options: (1) bring in fresh air from outside (2)remove the virus from inside air
A 2016 study suggests that an exchange rate of nine times per hour
reduced SARS, MERS and H1N1 spread in a Hong Kong hospital.
CO2 levels outside are just above 400 parts per million (ppm).
A well ventilated room will have around 800 ppm of CO2.
Any higher than that is a sign the room might need more ventilation.
The best virus removal option is a cleaner using a (HEPA) filter.
Trump orders cowed CDC to stop recommending tests for folks exposed to COVID-19
Testing only those with symptoms should soon boost real infected rates;
the CDC estimates that 40% of those infected with the coronavirus
have no symptoms but may spread it to other people.
https://www.cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html
Moderna reports that its mRNA vaccine candidate generated a promising immune response
in elderly patients in an early stage clinical trial. 10 adults between the ages of 56 and 70
and 10 elderly adults aged 71 and older received two 100 microgram doses of the vaccine 28 days apart.
The volunteers produced neutralizing antibodies at levels higher than those seen in recovered
COVID-19 patients, with no serious adverse events reported.
https://investors.modernatx.com/static-files/1dc3deaf-4a1b-46f8-8aed-33bfd7b2c979
Specific high-sensitivity enzymatic reporter unlocking (SHERLOCK) assay
using the enzyme Cas13a was 100% specific and 96% sensitive
with a fluorescence readout for the full range of viral load in the clinical samples.
https://www.nature.com/articles/s41551-020-00603-x
More data on blood thinner efficacy for COVID-19
All regimens of anticoagulants were far superior
(50% higher chance of survival, and roughly a 30% lower chance of intubation)
to no anticoagulants in COVID-19 patients. Among anticoagulants,
therapeutic and prophylactic subcutaneous low-molecular weight heparin,
and therapeutic oral apixaban may lead to better results.
https://medicalxpress.com/news/2020-08-blood-thinner-efficacy-covid-.html
Guidance on non-medical, reusable fabric masks
Three layers of fabric are typically required
The inner layer is in contact with the wearer's face - soft, absorbent
(i.e. hydrophilic, closely woven structure from cotton/cotton blends; silk).
The middle layer is either a filter (typically non-woven) in a pocket OR a non-woven structure
(e.g. melt-blown, needle-punched, other form) for which varied fibres/filaments/films are possible.
The outer layer is exposed to the environment and limits external contamination/ penetration through that layer
(hydrophobic - closely woven structure from polyester, polyamide/ blends, cotton).
First confirmed case of COVID-19 reinfection
"this is a textbook example of how immunity should work."
The 33-year-old man with mild symptoms first tested positive in late March in Hong Kong
and got reinfected with no symptoms about four months later while traveling in Spain.
DNA sequencing revealed two slightly different strains of the virus,
indicating the second infection was not just a lingering remnant of the first
"While immunity was not enough to block reinfection, it protected the person from disease."
[ no information about whether he could infect others while reinfected ]
FDA Commissioner Stephen Hahn admits overselling one convalescent plasma,
as he announced its emergency approval with the president Sunday night.
"I have been criticized for remarks I made Sunday night
about the benefits of convalescent plasma. The criticism is entirely justified."
https://medicalxpress.com/news/2020-08-health-touting-false-plasma.html
NIST has produced safe synthetic SARS-CoV-2 gene fragments
to help manufacturers produce more accurate and reliable diagnostic tests.
NIST is providing this material at no cost to researchers, test manufacturers
and testing laboratories as a "research grade test material,"
though NIST scientists are planning to further develop it into
the type of standard reference material (SRM) for which NIST is known.
https://www.nist.gov/programs-projects/sars-cov-2-research-grade-test-material
Altimmune's COVID-19 vaccine candidate, AdCOVID,
administered by a single intranasal spray,
shows potent T-cell responses in a preclinical study.
"The property that sets AdCOVID apart is that it has been shown preclinically
to induce a potent T-cell and IgA antibody response in the lungs, in addition to
the systemic neutralizing antibody response induced by intramuscular vaccine candidates"
Manufacturers of multi-analyte respiratory panels which include SARS-CoV-2
are now eligible for Emergency Use Authorization (EUA) from the FDA,
which noted their usefulness when multiple respiratory pathogens are circulating
at the same time, as is expected this flu season.
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm?ID=3704
A computational workflow using a series of open-source algorithms and webtools
identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II)
and 6 potential B cell epitopes that are predicted to have broad population coverage
and could serve as the basis for designing investigational peptide-based vaccines.
https://www.nature.com/articles/s41598-020-70864-8
Potent antiviral peptide P9R exhibits broad-spectrum antiviral activities against
the enveloped SARS-CoV-2, MERS-CoV, SARS-CoV, A(H1N1)pdm09, A(H7N9) virus,
and the non-enveloped rhinovirus.
https://www.nature.com/articles/s41467-020-17986-9
FDA EUA for distribution of COVID-19 convalescent plasma
[ credibility and scientific rigor are for sissies ]
Urged by Trump, studies to prove its benefits have NOT been completed.
FDA: "may be effective in treating COVID-19 and that the known
and potential benefits of the product outweigh the known and potential risks of the product"
https://www.fda.gov/media/141480/download
The risk of severe COVID-19 illness and death was reduced for patients
with high blood pressure who were taking Angiotensin-Converting Enzyme inhibitors
(ACEi) or Angiotensin Receptor Blockers (ARB).
https://link.springer.com/article/10.1007/s11883-020-00880-6
A Ben Affleck feature was supposed to film in the U.S., but a lack of readily available testing
material and quick lab results has
pushed production to Canada. Producers are also looking
at the U.K. and Australia as other possible safe havens for production
Pfizer and BioNTech say their COVID-19 vaccine candidate is
on track for regulatory review
as soon as October, if it continues to provide positive results. "If regulatory authorization
or approval is obtained, [we] currently plan to supply up to 100 million doses
worldwide by the end of 2020 and approximately 1.3 billion doses by the end of 2021."
Remdesivir doesn't significantly improve outcomes in moderate pneumonia from COVID-19
On day 11 of the study, 65% of patients in the 10-day remdesivir group had been discharged,
compared to 60% of patients not given the drug. 23% of patients in both groups
remained hospitalized and 6% in each group required supplemental oxygen.
In both groups, 2% of patients died.
https://jamanetwork.com/journals/jama/fullarticle/2769871
Mako Medical Laboratories, a six-year-old diagnostic company based in Raleigh, N.C.,
decided in 2020 to enter the nascent field of nutritional DNA,
making suggestions to optimize customers' diet based on their genomes.
The equipment and tools used to test DNA for nutritional recommendations
are also used for coronavirus testing. As other large diagnostic companies
like Quest and LabCorp struggle to process an enormous number of samples for testing,
Mako suddenly finds itself with capacity to spare, with 11 polymerase chain reaction testing machines
and 22 machines to purify RNA, which combined are capable of processing 384 samples at a time,
and 600 lab techs hired since April.
Once a sample is at the company's lab outside Raleigh, it takes only 6 - 8 hours for a lab tech
to purify it through RNA extraction and run it through one of the machines, which seeks
to identify the presence of three genes that in combination indicate a COVID-19 infection.
The company could process 25,000 to 30,000 samples a day, with turnaround less than 36 hours.
Trump administration bars FDA from regulating some laboratory tests, including for coronavirus
Tests manufactured by one company (e.g. Roche or Abbott) and sold to labs and other firms
are still regulated by the FDA and unaffected by the change.
Some public health experts argue the change is unlikely to solve current testing problems,
which at this point are largely due to shortages of supplies such as swabs and chemical reagents.
https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus
Nasal adenovirus vaccinations can shield mice from SARS-CoV-2
and might be more effective than an injected form of the same vaccine.
http://doi.org/d63k
Many animal species may be vulnerable to SARS-CoV-2 infection
25 amino acids of the ACE2 protein are important for the virus to infect humans.
"Animals with all 25 amino acid residues matching the human protein
are predicted to be at the highest risk for contracting SARS-CoV-2 via ACE2"
https://www.pnas.org/content/early/2020/08/20/2010146117
Research from the University of Notre Dame estimates that
more than 100,000 people were already infected with COVID-19 by early March,
when only 1,514 cases and 39 deaths had been officially reported.
https://www.pnas.org/content/early/2020/08/20/2005476117
A technique called CyTOF, which can track nearly 40 different protein markers at once,
helped identify characteristics of SARS-CoV-2 specific T cells in 9 recovered patients.
"Our findings suggest that while antibodies against SARS-CoV-2 may fade relatively quickly,
long-term immunity to the virus may be generated in the form of memory responses,
including that of memory T cells. To confer lasting and effective immunity against COVID-19,
vaccination strategies should strongly consider approaches that,
in addition to generating neutralizing antibodies,
elicit long-lived and multi-functional T cells against SARS-CoV-2."
http://dx.doi.org/10.1016/j.xcrm.2020.100081
COVID-19 and Seasonal Influenza: Preparing for a Collision
As the country grapples with this new surge in COVID-19 cases, another potential crisis
looms: flu season. Every fall and winter, seasonal influenza takes a devastating toll in the U.S.;
particularly among those over the age of 65 and under the age of 5. Hospitals fill up with
individuals needing respiratory support and schools serve as epicenters for community spread.
The challenges of seasonal influenza alone are great, but when combined with the COVID-19
pandemic, many cities and states could find the impact overwhelming.
https://drive.google.com/file/d/1KdnHBQbTA8AF3dmRdqL7C1AWW-83Qzrg/view
Pairing remdesivir with other drugs to improve effectiveness against COVID-19.
In a large NIH-sponsored clinical trial, remdesivir was shown to shorten recovery time
by 4 days, on average, but it did not reduce deaths. The third phase of a U.S. trial,
known as ACCT, will test either remdesivir and a placebo or remdesivir and beta interferon
on 1,000 patients. The first phase tested remdesivir alone,
and results of phase 2 testing remdesivir and a placebo against remdesivir and baricitinib
are still being evaluated. If phase 2 results had been persuasive,
that trial would have been halted and every patient given remdesivir and baricitinib.
https://www.nytimes.com/2020/08/18/health/Covid-treatments-remdesivir.html
Possible explanations for COVID-19 patients with extremely low oxygen levels
but no difficulty breathing:
"While a pulse oximeter is remarkably accurate when oxygen readings are high,
it markedly exaggerates the severity of low levels of oxygen when readings are low."
More than half of the patients had low levels of carbon dioxide,
which may diminish the impact of an extremely low oxygen level.
https://www.atsjournals.org/doi/10.1164/rccm.202006-2157CP
Immunoglobulin A (IgA) antibodies, such as MAb362,
may provide effective immunity against SARS-CoV-2.
MAb362 was originally isolated in SARS-CoV testing.
https://www.nature.com/articles/s41467-020-18058-8
Macaques are protected against SARS-CoV-2 challenge 30 days after
a single vaccination with a replication-incompetent recombinant serotype 5 adenovirus,
Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein.
https://www.nature.com/articles/s41467-020-18077-5
The COVID-19 outbreak that led to lost jobs, skyrocketing unemployment
and a giant decline in tourist travel and economic activity
has reduced SC's expected $1.8B budget surplus to nearer $700M.
https://www.thestate.com/news/coronavirus/article244428867.html
inhibiting 3CLpro; crap in U.S. fan (compared to early May)
Coronavirus 3C-like protease (3CLpro) is an enzyme essential for viral replication.
This research describes structure-guided optimization of a series of 3CLpro inhibitors.
Two selected compounds showed antiviral effects against SARS-CoV-2
in cultured primary human airway epithelial cells.
https://stm.sciencemag.org/content/12/557/eabc5332.full
Children are silent[?] spreaders of SARS-CoV-2
In a study of 192 children ages 0-22, 49 children tested positive for SARS-CoV-2,
and an additional 18 children had late-onset, COVID-19-related illness.
Infected children were shown to have a significantly higher level of virus in their airways
than hospitalized adults in ICUs for COVID-19 treatment.
"If schools were to reopen fully without necessary precautions,
it is likely that children will play a larger role in this pandemic"
https://www.jpeds.com/article/S0022-3476(20)31023-4/fulltext
ventilate
"So the air in your home probably changes over once every hour or two hours.
We're aiming for an air exchange rate of, like, six per hour."
If a fan meant to increase ventilation ends up blowing virus across people's faces,
it's self-defeating. Monitor using a CO2 detector.
Air filters can work - MERV-13 designation or higher
Biden's COVID-19 response plan
100 million tests per month, daily briefings by experts,
restore a biodefense official to the National Security Council,
and improve COVID-19 surveillance by revamping insurance claims data.
pharma politics: drug makers and trade groups shower $11M in 4500 checks on 356 candidates
Industry PACs have donated $8.62 million to individual candidates or their affiliated committees,
with another $2.59 million to broader political groups like the Moderate Democrats PAC,
the National Republican Senatorial Committee, and other drug industry PACs, including PhRMA's.
https://www.statnews.com/feature/prescription-politics/prescription-politics/
FDA halts COVID-19 blood plasma emergency approval
As the FDA was prepping to allow emergency use of blood plasma donation
from recovered COVID-19 patients, authorization was put on hold for now
as more data are reviewed, and H. Clifford Lane, M.D., clinical director
at the National Institute of Allergy and Infectious Diseases,
said an emergency approval could still be issued in the near future.
3 blood molecules (IP-10, interleukin-10 and interleukin-6) predict COVID-19 progression
The triad was found to be a more rigorous predictor of disease severity
than commonly-used clinical indicators, including C-reactive protein (CRP), D-dimer or ferritin.
https://www.nature.com/articles/s41591-020-1038-6
Transcranial Doppler detects brain microbubbles in COVID-19 patients
The study suggests blood may be detoured from clogged vessels
to unusually widened ones and thus flowing through too fast to properly absorb oxygen.
https://www.atsjournals.org/doi/10.1164/rccm.202006-2219LE
Mathematical modeling in the age of COVID-19
Modeling the epidemiology, lungs and disease processes
Compared with seasonal flu, coronavirus disease has a number of features:
a longer incubation period (on average about 5 days, but can reach several weeks),
higher mortality (estimated at 2-4%, although accurate estimates are not yet possible),
a large number of asymptotic cases (but possibly transmitting the infection),
a large number of cases with a severe course of the disease
and complications to other organs (mainly lungs).
Models based on ordinary differential equations do not take into account
a possible spatial distribution or heterogeneity of infected individuals
and of other population sub-classes.
The CUNY School of Medicine at The City College of New York and TechnoVax, Inc.
have generated and characterized SARS-CoV-2 virus-like particles (VLPs)
which are structural mimics of the native virus in size, morphology and surface composition
but devoid of viral, infection causing, genetic material.
"This innovation is most likely to accelerate the development of a COVID-19 vaccine
in that it utilizes a proven technology
that is distinct from current COVID-19 vaccine candidates," said Jose Galarza, CEO, TechnoVax.
https://www.ccny.cuny.edu/news/cuny-med-school-technovax-report-covid-19-vaccine-breakthrough
Machine learning study constructed a signature using 7 lab features
to predict SARS-CoV-2 pneumonia outcome based on findings of 110 patients.
[ This signature does not appear to have been tested on other patient data;
may be liable to over-training ]
https://www.nature.com/articles/s41598-020-71114-7
Roche and Regeneron collaborate to increase global supply of REGN-COV2
investigational antibody combination for COVID-19 by at least three and a half times.
REGN-COV2 is currently in two Phase 2/3 COVID-19 treatment clinical trials and in
a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals.
https://www.roche.com/media/releases/med-cor-2020-08-19.htm
I was recently asked about [dis]comfort away from our abode.
This plot compares new cases for the most recent 20 days to the first 20 days of May,
i.e. before Memorial Day, when crap hit the U.S. fan:
As usual, gray bars represent total cumulative cases
but red bars represent new cases in most recent 20 days,
with lighter red for fewer and darker red > May 1-20.
Note that scale remains logarithmic; e.g.
distance from 1 to 30 is the same as from 30 to 900.
IMO, folks in St. Lawrence NY could feel relatively comfortable;
Beaufort had ~ 20/100k in May but now has 600/100k...
Some might argue (because some LOVE to argue) that COVID-19 is on average
contagious for < 20 days, but reported cases understate actuals,
with most cases reported AFTER what is believed to be peak contagion.
accuracy issues with Thermo Fisher's TaqPath COVID-19 test kit and software
One of the first commercial tests granted EUA and basis for several diagnostics,
software updates and better mixing
to mitigate false positive results are "recommended".
'Test-&-trace' necessary but not sufficient
Immediate testing with the onset of symptoms and results within 24 hours,
identifying 80% of cases and quarantining of contacts (also within 24 hours)
can reduce COVID-19 reproduction rate by 26%.
https://spiral.imperial.ac.uk/handle/10044/1/80910
Dexamethasone helpful for COVID-19 acute respiratory distress syndrome (ARDS)
Overall pooled mortality among 10,815 ARDS cases in COVID-19 patients was 39%;
median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28%.
https://www.tandfonline.com/doi/full/10.1080/17476348.2020.1804365
Machine learning identifies on-target imatinib versus off-target drugs for inhibiting SARS-CoV-2
Chloroquine and hydroxychloroquine are prototypic lysosomotropic and autophagy-inhibitory drugs,
yielding some encouraging results in uncontrolled observational studies,
but ultimately failing in randomized COVID-19 trials.
Other lysosomotropic agents are expected to similarly fail
due to their non-specific (i.e. off-target) mode of action,
which may also explain side effects such as arrhythmia. In contrast,
others (e.g. remdesivir, by injection) may mediate their effects through specific mechanisms.
Oral treatment of COVID-19 with imatinib
https://en.wikipedia.org/wiki/Imatinib
(which is now off-patent and hence available as a generic at a reduced cost)
is being evaluated in clinical trials
and is the sole agent known to inhibit CoVs replication through an on-target effect.
https://www.nature.com/articles/s41419-020-02842-x
A company called nference has recently developed a software platform
with the stated goal of synthesizing all the world's biomedical knowledge.
altered or loss of sense of smell and/or taste are the earliest specific indicators
of impending COVID-19 diagnosis, up to 4-7 days ahead of the typical PCR testing date.
a majority of the long-term viral RNA shedders are not hospitalized and are asymptomatic.
IgG-seropositive individuals can still shed viral RNA, emphasizing the need for
monitoring viral loads and neutralizing antibody titers in long-term SARS-CoV-2 RNA shedders.
in collaboration with the Mayo Clinic, developed and deployed an epidemiological tracking
platform that integrates the SARS-CoV-2 PCR testing data at the county level across the U.S.
and enables measuring and predicting spatio-temporal "hot spots".
"This study looked at a molecular process that the coronavirus uses to control
how it makes the viral proteins it needs to replicate itself, called frameshifting.
Because one of the products of frameshifting is the enzyme that the virus uses
to replicate itself, frameshifting is a promising target for potential drugs."
"... what we've learned about frameshifting in the original SARS virus
can also be applied to the new coronavirus."
http://dx.doi.org/10.1074/jbc.AC120.013449
Ahoy, immunity: first statistically-significant evidence of COVID-19 acquired immunity
120 of 122 crew members tested negative for SARS-CoV-2; 104 were subsequently infected.
Tests for none of those infected had shown neutralizing antibodies, but
all 3 with neutralizing antibodies avoided reinfection.
https://www.medrxiv.org/content/10.1101/2020.08.13.20173161v1
Corona Accelerated R&D in Europe (CARE), with $92.5 million funding from the EU
and 11 members of the European Federation of Pharmaceutical Industries and Associations,
has three goals:
screen libraries to identify existing compounds that can be repurposed against COVID-19
perform in silico screening to find new small molecules against SARS-CoV-2
and "future coronavirus targets"
apply approaches such as fully human phage and yeast display
to the discovery of virus-neutralizing antibodies.
Just weeks after ExeVir Bio was spun out of a Belgian research institute
to develop a llama-inspired antibody treatment for COVID-19,
a rival effort at the University of California, San Francisco
reports promising preclinical results for its aerosol formulation "AeroNabs"
and suggests it could be self-administered.
https://www.biorxiv.org/content/10.1101/2020.08.08.238469v1.full.pdf
As more children are tested for COVID-19,
their ability to get infected and spread the coronavirus is becoming more clear.
[
includes chart if child cases by state ]
It's embraced by Housing and Urban Development Secretary Ben Carson
and MyPillow founder and CEO Mike Lindell, a big Trump backer,
who helped Andrew Whitney of Phoenix Biotechnology
get an Oval Office meeting in July to promote oleandrin.
FDA's Hahn appears to be resisting Whitney's efforts - at least so far -
despite Trump expressing his enthusiasm for the FDA to approve oleandrin.
"... presymptomatic transmission of SAR-CoV-2 is not only plausible,
but quite possibly a substantial mode of transmission,
especially in the presence of public health interventions."
https://www.nature.com/articles/s41591-020-1049-3
Nucleocapsid, open reading frame (ORF)8 and ORF3b antibodies,
taken together as a cluster of points, identified 96.5% of COVID-19 samples
at early and late time points of disease with 99.5% specificity.
https://www.nature.com/articles/s41590-020-0773-7
Data from integrated docking simulations, with molecular dynamics (MD),
Supervised MD and Steered MD simulations
to identify a Spike protein - ACE2 interaction inhibitor
showed that Simeprevir and Lumacaftor bind the receptor-binding domain
of the Spike protein with high affinity and prevent ACE2 interaction.
https://www.nature.com/articles/s41598-020-70863-9
Another three mRNA vaccine candidates for COVID-19:
RQ3011-RBD contains an mRNA encoding the receptor binding domain
of spike (S) glycoprotein with a C-terminal membrane-anchoring helix.
https://en.wikipedia.org/wiki/C-terminus
RQ3012-Spike contains an mRNA encoding the full-length wild-type S.
RQ3013-VLP contains three mRNAs encoding S, membrane, and envelope proteins
that can assemble into virus-like particles.
https://www.nature.com/articles/s41422-020-00392-7
A virion is a complete viral particle, consisting of RNA or DNA
surrounded by a protein shell and constituting the infective form of a virus.
A protein trimer is formed by three, usually non-covalently bound, macromolecules.
Cryo-electron microscopy and tomography here images intact SARS-CoV-2 virions,
determining high-resolution structure, conformational flexibility and distribution
of spike protein trimers in situ on the SARS-CoV-2 virion surface.
https://www.nature.com/articles/s41586-020-2665-2_reference.pdf
Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection
Even among COVID-19 patients succumbing to pneumonia, autopsies identify
distinctly different populations, i.e. high and low viral RNA.
https://www.medrxiv.org/content/10.1101/2020.07.30.20165241v1.full.pdf
The latest systematic review from the Norwegian Institute of Public Health shows that
distances of 1 meter or more reduce the risk of infection by an estimated 80%.
Face masks used in the population only reduce the risk by approximately 40%.
https://medicalxpress.com/news/2020-08-masks.html
According to CDC, pharmaceutical companies plan to make around 196 million flu
vaccine doses to serve the U.S. population of 330 million, up from 175 million last year.
CVS, which administers flu vaccines without prescription,
is ordering 18 million doses, double the 2019 amount.
Vaccine maker Seqirus plans to increase U.S. production by roughly 15%
- from 52 million to 60 million doses, as does Sanofi - from 70 to 80 million.
Yale's open source SalivaDirect test gets FDA EUA
Yale intends to provide the SalivaDirect protocol, which requires neither special swabs
nor a separate nucleic acid extraction step, to laboratories as an "open source" protocol,
meaning that designated laboratories could follow the protocol to obtain the required components
and perform the test in their lab according to Yale's instructions for use.
Because this test does not rely on any proprietary equipment from Yale
and can use a variety of commercially available testing components,
it can be assembled and used in high-complexity labs throughout the country,
provided they comply with the conditions of authorization in the EUA.
Instead of restructuring daily life around the American way of testing,
the country should
build testing into the American way of life.
Paper strip tests, e.g. from https://e25bio.com which deliver results in 15 minutes or less,
should become a ubiquitous part of daily life. Before anyone enters
a school or an office, a movie theater or a Walmart, they must take one of these tests.
Test negative, and you may enter the public space. Test positive, and you are sent home.
CDC "clarifies" that its updated quarantine guidance
does not imply people who are infected with the coronavirus are immune to reinfection.
Instead, it "simply suggests retesting someone
in the following three months after their initial infection is unnecessary
unless that person shows symptoms that can't be associated with another illness."
https://www.cdc.gov/media/releases/2020/s0814-updated-isolation-guidance.html
Based in Tuebingen in southwest Germany,
CureVac has one of the leading COVID-19 vaccine candidates
and received permission in June to start human trials. It was thrust into the spotlight
in March when Trump's administration was looking to secure exclusive rights to its vaccine.
The German government in June took a 23% stake in CureVac for 300 million euros.
In July, British pharma giant GlaxoSmithKline paid around 143 million euros
for a 10% stake in the company to work together on vaccine development.
NIAID has "begun efforts to manufacture a strain that could be used
to develop a human challenge model, if needed"
"A 20-year-old in a challenge study isn't really going to give us the answer of
will this vaccine keep an older person, someone with chronic kidney disease,
from ending up in the hospital"
University of Alabama at Birmingham and Polish researchers propose that
SARS-CoV-2 acts as a microRNA "sponge," modulating host microRNA levels
in ways that aid viral replication and stymy host immune response.
https://journals.physiology.org/doi/abs/10.1152/ajplung.00252.2020
According to researchers at The University of Texas MD Anderson Cancer Center,
antibodies to the SARS-CoV-2 spike protein receptor binding domain (S-RBD)
are speculated to neutralize virus infection,
while the SARS-CoV-2 nucleocapsid protein (N-protein) antibody
may often only indicate exposure to the virus, not protections against reinfection.
3% of healthy and non-COVID-19 samples collected during Houston's pandemic
were positive for the N-protein antibody, but only 1.6% of those had the S-RBD antibody.
Of samples with the S-RBD antibody, 86% had neutralizing capacity
- meaning they could prevent reinfection of COVID-19,
but only 74% of samples with N-protein had neutralizing capacity.
When positive for both, 96.5% exhibited neutralizing capacity.
https://insight.jci.org/articles/view/142386
Molecular Characterization of Ebselen Binding Activity to SARS-CoV-2 Main Protease
Given its essential role in proteolytic processing, the main protease Mpro has been identified
as an attractive candidate for drugs against SARS-CoV-2 and similar coronaviruses.
Recent high-throughput screening studies have identified existing, small-molecule drugs
as potent Mpro inhibitors. Amongst these, Ebselen (2-Phenyl-1,2-benzoselenazol-3-one),
a glutathione peroxidase mimetic seleno-organic compound, is particularly attractive.
Recent experiments suggest that its effectiveness is higher than that of other molecules
that also act at the enzyme catalytic site.
Relying on extensive simulations with all-atom models, this study examined at a molecular level
the potential of Ebselen to decrease Mpro catalytic activity.
Results indicate that Ebselen exhibits a distinct affinity for the catalytic site cavity of Mpro.
In addition, molecular models reveal a second, previously unknown binding site for Ebselen
in the dimerization region localized between the II and III domains of the protein.
A detailed analysis of the free energy of binding indicates that the affinity of Ebselen
to this second binding site is in fact significantly larger than that to the catalytic site.
https://arxiv.org/abs/2005.09805
RS-CoV-2 immunological memory in peripheral blood mononuclear cells (PBMCs)
Adaptive immune repertories underlie pathogenesis and recovery
in severe versus mild COVID-19 patients.
https://www.nature.com/articles/s41392-020-00263-y
Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions
No infectivity in liquid medium at room temperature after 4 days.
COVID-19 virus can survive for 3 days in liquid medium or on dry filter paper.
SARS-COV-2 at a certain high titer might survive the acidic environment of the stomach
for a certain period.
https://www.nature.com/articles/s41421-020-00191-9
SARS-CoV-2 herd immunity at a population-wide infection rate of ~40%
.. by introducing age and activity heterogeneities into population models
A mathematical model with proportion of infected individuals in groups
with high contact rates greater than that in groups with low contact rates.
One of the simplest of all epidemic models is to assume
a homogeneously mixing population
in which all individuals are equally susceptible
and equally infectious if they become infected.
Two important features known to play an important role in disease spreading were added:
1) divide the herd into 6 age groups and fit contact rates derived from an empirical study
2) categorize individuals into three different activity levels,
which are arbitrary and chosen for illustration purposes:
50% of each age cohort have normal activity,
25% have half as many contacts compared with normal activity, and
25% have twice as many contacts as normal activity.
Individuals who get infected are assumed to be initially latent for a mean of 3 days,
followed by an infectious period of a mean of 4 days. After a month,
preventive measures are implemented such that
all averages in the next-generation matrix are scaled by the same factor a < 1.
These preventive measures are kept until the ongoing epidemic is nearly finished.
That is, all preventive measures are relaxed thus setting a back to 1 after 3.5 months
If herd immunity is not reached, then there will then be a second wave,
whereas if herd immunity has been achieved, the epidemic continues to decline.
[ this amounts to a more ambitious version of a model I made in March. ]
https://science.sciencemag.org/content/369/6505/846
Estimation of incubation period distribution of COVID-19 using disease onset forward time:
A novel cross-sectional and forward follow-up study based on
1084 cases of patients who contracted COVID-19 in Wuhan, then left.
The estimated median incubation period was 7.76 days
[95% confidence interval (CI): 7.02 to 8.53],
and the 90th percentile was 14.28 days (95% CI: 13.64 to 14.90).
[ personally, I expect incubation time depends on amount of virus inhaled ]
https://advances.sciencemag.org/content/6/33/eabc1202
A group of six biopharmaceutical firms researching monoclonal antibody (mAb) candidates
recently sought [and the U.S. Department of Justice (DOJ) granted] permission
under antitrust law to exchange "technical information"
on each other's manufacturing processes and platforms (but not information on cost or price).
https://science.sciencemag.org/content/early/2020/08/12/science.abc9588
Mass cytometry was used to assess immune responses to SARS-CoV-2 infection in
52 COVID-19 patients that were confirmed positive for viral RNA by PCR and
62 age and gender-matched healthy controls distributed between two independent cohorts,
1) the Princess Margaret Hospital at Hong Kong University,
2) the Hope Clinic at Emory University in Atlanta, GA
There was a striking increase in the frequency of plasmablast and effector CD8 T cells
in all infected individuals in both cohorts. Of note, the kinetics of the CD8 effector T cell response
was prolonged and continued to increase up to day 40 post onset of symptoms.
These results suggest that SARS-CoV-2 infection results in a spatial dichotomy
in the innate immune response, characterized by suppression of peripheral innate immunity,
in the face of proinflammatory responses reported in the lung.
https://science.sciencemag.org/content/early/2020/08/10/science.abc6261
Between 2009 and 2019, U.S. flu vaccine effectiveness ranged from 19% to 60%.
Immunity from a shot in early Fall can dissipate before winter's end.
B cells reside in bone marrow and make antibodies that can attach to and disable viruses,
taking several days after an infection to produce high levels of antibodies
- a disadvantage in influenza, which can cause disease rapidly. Adjuvants boost vaccine
effectiveness by acting as irritants, ramping up the immune response.
Developed in the 1940s, the first influenza vaccines used adjuvants,
but caused ulcers at injection sites and were dropped from later vaccines.
A revamped influenza vaccine that has an oil-in-water adjuvant
- the water shields the oil and makes it safer - has been used in Italy since 1997
and was approved by European and U.S. regulators in 2000 and 2015, respectively.
https://science.sciencemag.org/content/early/2020/08/12/science.aaz8432
In a July 31 letter, the Healthcare Infection Control Practices Advisory Committee
described hospitals as "scrambling" to determine how to meet new daily COVID-19
reporting requirements to the U.S. Department of Health and Human Services,
and said retiring the older system jeopardized data integrity.
"Moving forward, it will be even more challenging to perform meaningful inter-state
comparisons, and to understand which COVID-19 mitigation strategies were successful
(or failed)."
https://cdn.cnn.com/cnn/2020/images/08/13/hicpac.hhs.data.letter.sent.to.cnn.pdf
Thursday, Matthew McConaughey interviewed Dr. Anthony Fauci for 40 minutes on Instagram.
What about letting everyone get infected so we all become immune and the disease dies out?
"If everyone contracted it ... a lot of people are going to die," Fauci said.
"The death toll would be enormous and totally unacceptable," Fauci added.
"And that's the reason why we're against saying,
'Let it fly. Let everybody get infected and we'll be fine.' That's a bad idea."
https://www.instagram.com/p/CD2WoXupHV-/
The House Select Subcommittee on the Coronavirus Crisis is questioning
how vaccines are being chosen for accelerated development under Operation Warp Speed
and calling for details on possible
conflicts of interest among those making the choices.
If a COVID-19 vaccine is proven effective,
the U.S. will ensure free distribution for all Americans,
officials said Thursday, underscoring there will be no shortcuts on safety.
Doctors or clinics that administer them will have to be paid
but these costs should mostly be covered by private and public insurers.
https://medicalxpress.com/news/2020-08-covid-vaccine-free-americans.html
PDS Biotechnology, a clinical stage immunotherapy company, has announced
positive results from preclinical testing conducted at the University of Kentucky College of Medicine
of its COVID-19 vaccine candidate, PDS0203.
PDS0203 stands out among COVID-19 vaccines currently in development
because it includes a vaccine technology pioneered by PDS Biotech called Versamune,
which stimulates important parts of the immune system to activate T cells.
President Trump's coronavirus task force warns that Georgia continues to see
"widespread and expanding community viral spread"
and that the state's current policies aren't enough to curtail COVID-19.
The Atlanta Journal-Constitution obtained, from a source,
the White House Coronavirus Task Force recommendations for Georgia, dated Aug. 9.
Dr. Melanie Thompson, principal investigator of the AIDS Research Consortium of Atlanta,
said it is frustrating that
the report is only seeing the light of day because of a leak.
Sinopharm shares phase 2 data on inactivated COVID-19 vaccine
The phase 1 and 2 results suggest the vaccine may be safe, tolerable
and capable of triggering production of antibodies against the coronavirus.
https://jamanetwork.com/journals/jama/fullarticle/2769612
Penn State students required to sign COVID-19 liability waiver to participate in Fall semester
While not alone in asking students to assume risk of COVID-19,
Penn State's compact is "on the more extreme end," said Heidi Li Feldman,
a professor at Georgetown University Law Center who focuses on legal liability.
A handful of colleges and universities across the country have started
to ask students to sign liability waivers in advance of returning to campus.
Inovio boasted to Trump about its COVID-19 vaccine;
experts are sceptical
In 2009, the small biotech company in PA rushed to develop an H1N1 vaccine.
After announcing promising early results, Inovio's stock soared more than 1,000%.
Riding the momentum, the company sold more shares to the public. Since then,
Inovio has announced encouraging news about its work on vaccines for malaria,
the Zika virus and even a cancer vaccine. Upbeat declarations have caused
the company's stock price to leap, enriching investors and senior executives.
There's only one catch: Inovio has never actually brought a vaccine to market.
While there are some early signs of promise with its COVID-19 vaccine,
Inovio has released only bare-bones data from the first phase of clinical trials. It is locked in
a legal battle with a key manufacturing partner which claims that Inovio stole its technology.
While it claims to be part of Operation Warp Speed, Inovio is not on the list of companies
selected to receive financial support to mass-produce vaccines.
Shareholders have sued Inovio, claiming it has exaggerated its progress.
how states are (not) doing
Public health experts look at 4 metrics to determine how bad things are:
the number of daily new cases, the infection rate (how likely is virus spread),
the percent of tests that are positive (which should be low in states with sufficient testing),
and the percent of hospital beds occupied by very sick patients.
Howard Hughes Medical Institute investigators have published
an interactive map cataloging how nearly 4,000 different mutations
alter SARS-CoV-2's ability to bind to human cells.
"We don't know how the virus will evolve, but now we have a way
to look at the mutations that can occur and see their effects"
https://www.hhmi.org/news/a-new-map-catalogs-the-effects-of-coronavirus-mutations
Results from a study that tracked 350 severely ill COVID-19 patients admitted to
Houston Methodist's 8 hospitals from March 28 through July 6 offer evidence that
transfusing critically ill COVID-19 patients with high antibody plasma early in their illness
- within 72 hours after hospitalization proving most effective - reduced their mortality rate.
Several studies show that the more than 34,000 COVID-19 patients in the U.S.
who have received plasma transfusions for COVID-19 experienced minimal adverse effects.
https://ajp.amjpathol.org/article/S0002-9440(20)30370-9/fulltext
According to a newly published multivariable analysis in "Vaccines",
significantly improved COVID-19 outcomes are associated with
BCG vaccinations received by ages 24 or younger in the last 15 years.
There was no effect among older adults.
https://www.mdpi.com/2076-393X/8/3/378
A fluorescence-based assay that detects SARS-CoV-2 neutralizing antibodies in patient specimens
and yields comparable results to plaque reduction neutralizing assay,
the gold standard of serological testing.
The reporter virus assay is superior to many antigen/antibody binding assays
because it measures functional SARS-CoV-2 neutralizing activity in the specimens.
https://www.nature.com/articles/s41467-020-17892-0
Liver damage in patients dying of COVID-19
a series of 40 autopsies including clinical, histologic, and virologic data
PCR of liver tissue was positive in 11 of 20 patients tested (55%).
https://www.nature.com/articles/s41379-020-00649-x
Mathematically modeling the epidemiological impact of face masks
(inf == infected) c, g respectively represent least, most effective mask
Inflection points occur at the point where supplies are exhausted,
and the outbreak continues with no new individuals adopting masks.
30% of infections are assumed to be undetected.
https://www.nature.com/articles/s41467-020-17922-x
Vir Biotechnology Inc plans to start
a mid-to-late stage trial in August
of COVID-19 drug candidate VIR-7831, a monoclonal antibody,
with initial clinical data from the study expected to be available before the end of 2020.
Vir Biotech has two other COVID-19 antibody candidates in development,
VIR-2703 and VIR-7832, and expects both to start human clinical trials later this year.
In March, Vir received a $250 million investment from British drugmaker GlaxoSmithKline Plc
as part of a collaboration to develop COVID-19 antibody treatments.
Putting the Public Back in Public Health - Surveying Symptoms of COVID-19
To date, most projections of the COVID-19 burden have been based on
incidence calculated from COVID-19 testing, hospitalizations, and deaths.
However, such estimates are severely limited.
New and cost-efficient participatory syndromic-surveillance tools have been developed
that can be used in real time to rapidly address critical near-term needs.
These tools work by capturing data on reported symptoms using mobile technology
such as phone apps or Internet-based questionnaires, which often provide
more timely signals of infectious disease transmission than more traditional sources. Covid Symptom Study app CovidNearYou
https://www.nejm.org/doi/full/10.1056/NEJMp2016259
Companies test COVID-19 antibody drugs
It can take a month or two after vaccination or infection
for the most effective antibodies to form naturally.
Companies are rushing to test drugs that deliver antibodies to fight the virus right away,
without having to train the immune system to make them.
"If we can generate them in large concentrations, in big vats in an antibody factory
... we can kind of bypass the immune system."
These drugs are believed to last for a month or more
and could give quick, temporary immunity to people at high risk of infection,
such as health workers and housemates of someone with COVID-19.
Eli Lilly has already started manufacturing its antibody drug,
betting that studies now underway will give positive results.
https://apnews.com/c37c678dbe18cd500e4cae916b44205a
Cleveland Clinic researchers have developed and validated a risk prediction model
(called a nomogram) that can help physicians predict which patients who have
recently tested positive for SARS-CoV-2 are at greatest risk for hospitalization.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237419
masks and PPE with hydrophilic surfaces could reduce infection risk
"Our calculations of the drying time as a function of contact angle
show that the droplet dries roughly four times faster on the hydrophilic surface
that attracts water than on the one that repels water.
This will drastically reduce the chances of virus survival"
https://aip.scitation.org/doi/10.1063/5.0020249
Moderna Inc. reached a deal with the Trump administration
to supply 100 million doses of its experimental vaccine for COVID-19,
in a pact valued at up to $1.5 billion, the latest in a string of supply agreements
the U.S. has reached to stockpile the most advanced vaccines in testing.
Public release of hospital data about the coronavirus pandemic has slowed to a crawl,
one month after the federal government ordered states to report it
directly to the Department of Health and Human Services and bypass the CDC.
Key indicators, such as estimates of the portion of inpatient beds occupied by COVID-19 patients,
are lagging by a week or more, making it harder for citizens and local officials
to get a handle on how the pandemic is progressing and for agencies to allocate supplies...
https://www.axios.com/hhs-hospital-data-coronavirus-9256f863-f5d4-4371-a658-bbdec4690709.html
By analyzing the immune response in 76 people with COVID-19 and in 69 healthy people,
investigators at the Stanford University of Medicine and other institutions
found enhanced levels of molecules that promote inflammation in the blood of severely ill COVID-19 patients.
Three of the molecules identified have been shown to be associated with lung inflammation
in other diseases but had not been shown previously in COVID-19 infections.
Key cells of the innate immune system in the blood of COVID-19 patients
became increasingly paralyzed as the disease got worse.
https://science.sciencemag.org/content/early/2020/08/10/science.abc6261
McMaster University and the University of Waterloo researchers found very low levels
of ACE2 receptor in human lung tissue. "Our finding is somewhat controversial,
as it suggests that there must be other ways, other receptors for the virus,
that regulate its infection of the lungs."
https://erj.ersjournals.com/content/early/2020/07/06/13993003.01123-2020
Their findings have been confirmed
independently by other researchers in Molecular Systems Biology.
https://www.embopress.org/doi/10.15252/msb.20209610
Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs
25% of COVID-19 patients reported digestive symptoms, among which
pharyngalgia [inflammation of the back of the throat] (7/48) was most common,
followed by diarrhea (3/48), anorexia (3/48), and nausea (1/48).
https://www.nature.com/articles/s41420-020-00307-w
San Diego-based Arcturus Therapeutics has begun a phase 1/2 trial of its
COVID-19 vaccine candidate ARCT-021 in collaboration with Duke-NUS Medical School in Singapore.
ARCT-021 generated neutralizing antibodies against the SARS-CoV-2 coronavirus
after a single 2-mcg dose in preclinical studies. Clinical study data expected in Q4 2020
Using nanometer-level simulations, Northwestern University researchers discovered
a positively charged site (known as the polybasic cleavage site) located 10 nanometers from
the actual binding site on the spike protein. The positively charged site allows strong bonding
between the virus protein and the negatively charged human-cell receptors.
A negatively charged molecule was designed that binds to cleavage sites,
blocking and inhibiting virus bonding to host cells. "We didn't expect to see
electrostatic interactions at 10 nanometers. In physiological conditions,
all electrostatic interactions no longer occur at distances longer than 1 nanometer."
https://pubs.acs.org/doi/10.1021/acsnano.0c04798
A colorimetric RT-LAMP assay and LAMP-sequencing
for detecting SARS-CoV-2 RNA in clinical samples.
Loop-mediated isothermal amplification (LAMP) is a faster alternative
to quantitative PCR that requires fewer resources. Sadly, LAMP is
less sensitive (resulting in false negatives) e.g. for patients recently infected.
This paper goes into practical details and considerations.
https://stm.sciencemag.org/content/12/556/eabc7075
Sars-Cov-2 viruses can be inactivated by commercially available mouthwashes.
Researchers tested 8 mouthwashes with different ingredients
that are available in pharmacies or drugstores in Germany.
No virus could be detected after an exposure time of 30 seconds to 3 of those:
Listerine cool mint (ethanol, essential oils),
Iso-Betadine mouthwash 1.0% (polyvidone-iodine),
Dequonal (dequalinium chloride, benzalkonium chloride)
"Gargling with a mouthwash cannot inhibit the production of viruses in the cells,
but could reduce the viral load in the short term
where the greatest potential for infection comes from, namely in the oral cavity and throat
- and this could be useful in certain situations,
such as at the dentist or during the medical care of COVID-19 patients."
https://watermark.silverchair.com/jiaa471.pdf
A new algorithm to rapidly screen for COVID-19
"All patients entering the ER routinely undergo a so-called quick scan,
which tests blood for no less than 30 different values. We wondered whether
there were subtle changes in the blood samples that are also characteristic of COVID-19.
We tried to find an instantly recognizable barcode, so to speak.
And, as it turned out, we were able to find one!"
Omeros reports trial results showing its drug
narsoplimab improved recovery and survival
for patients with acute respiratory distress syndrome associated with COVID-19
Dr. Sonia Angell resigns as CA Department of Public Health director and state public health officer
A computer server suffered an outage on July 25, then the state did not renew a certificate
for an intermediary to one of the country's biggest commercial labs. As a result,
the state did not receive 300,000 records from the lab for five days. The glitch
came at a time when case numbers played a vital role in school reopening decisions.
The U.S. International Development Finance Corporation (DFC) delays $765M Kodak loan
A day before the loan was officially announced,
more than 1 million shares of Kodak stock exchanged hands,
roughly quadruple its daily average.
https://www.washingtonpost.com/business/2020/08/10/kodak-stock-sec/
Based on findings from the world's largest metabolomic study to date,
Nightingale Health will launch a blood test to predict
if a person will develop mild symptoms or become severely ill due to COVID-19.
"These novel findings provide a scalable solution for personalized prevention
and population-level screening, which can later also be used
to prioritize vaccines for those who need it the most"
Nuclear magnetic resonance metabolomics was used to quantify
a comprehensive biomarker profile in 105,146 plasma samples (correlation 0.83).
https://www.medrxiv.org/content/10.1101/2020.07.02.20143685v1
Some drugs developed for cancer inactivate human enzymes, known as protein kinases.
"By targeting the host and not the pathogen itself, we remove the possibility for the pathogen
to rapidly become resistant by mutating the target of the drug,
as the target is made by the human host, not the pathogen."
"This has proven successful for other human pathogens including malaria and Hepatitis C virus,
and there are now very real prospects to use it
to discover novel drug targets for Hepatitis B and COVID-19"
https://www.nature.com/articles/s41467-020-17829-7
RMIT University Professor Christian Doerig's team will now collaborate
with the Peter Doherty Institute for Infection and Immunity (Doherty Institute)
to investigate potential COVID-19 treatments using this approach,
supported by funding from the Victorian Medical Research Acceleration Fund
in partnership with the Bio Capital Impact Fund (BCIF).
Surface Chemistry Can Unlock Drivers of Surface Stability of SARS-CoV-2
in Variety of Environmental Conditions
"We hope that this article will assist experimental scientists worldwide
in their investigations for unraveling the molecular drivers
implicated in this new coronavirus transmission from the surfaces
as well as in vaccine development and antiviral drug design"
https://www.cell.com/chem/pdf/S2451-9294(20)30411-3.pdf
FDA revokes EUA for China-based Autobio Diagnostics' COVID-19 antibody test.
"The agency has concluded that it is unlikely that
this test is effective in detecting SARS-COV-2 IgM antibodies and that
the known and potential benefits of its use do not outweigh the known and potential risks"
https://www.fda.gov/media/140908/download
FDA grants EUA for a manual version of
Vela Diagnostics' ViroKey SARS-CoV-2 RT-PCR diagnostic
for use on ABI 7500 Fast Dx instruments in qualified laboratories.
The test has also earned a CE mark in Europe and a provisional approval in Singapore.
This work illustrates the importance of the delivery route to vaccine effectivity:
Intramuscular delivery of ChAd-SARS-CoV-2-S protected against lung pathology
but did not clear the infection of the upper respiratory tract after SARS-CoV-2 challenge.
However, when administered intranasally, it induced local neutralizing antibody
and T cell responses that provided superior protection to both the upper and lower respiratory tract,
with no signs of viral replication 8 days post viral challenge.
The presence of tissue-resident memory T cells in the lung suggested long-lasting protection.
https://www.nature.com/articles/s41577-020-00422-w
In a new study, although Spike-targeted IgG (IgG-S) declined over time,
it remained detectable at relatively high levels until the end of the 6-month study period.
IgG-S titres correlated closely with neutralizing capacity.
https://www.nature.com/articles/s41577-020-00423-9
Bill Gates: most U.S. COVID-19 tests are 'completely garbage' and 'wasted'
Results take too long; medical providers shouldn't receive payment for COVID-19 tests
unless they can produce results within 48 hours.
"...for the rich world, we should largely be able to end this thing by the end of 2021,
and for the world at large by the end of 2022."
[ a mostly depressing, although IMO credible, interview ]
https://www.wired.com/story/bill-gates-on-covid-most-us-tests-are-completely-garbage/
Winter is coming: Why America's window of opportunity to beat back COVID-19 is closing
Cold and flu season is all but sure to complicate the task of figuring out
who is sick with COVID-19 and who is suffering from a less threatening respiratory tract infection.
Cherished outdoor freedoms that link us to pre-COVID-19 life
- pop-up restaurant patios, picnics in parks, trips to the beach -
will soon be out of reach, at least in northern parts of the country.
"We seem to be choosing leisure activities now over children's safety in a month's time.
And I cannot understand that tradeoff." An estimated quarter of a million motorcyclists
were expected to descend on Sturgis SD this past weekend for an annual rally that spans 10 days.
The U.S. is racking up more cases in a week
than Britain has accumulated since the start of the pandemic.
Novel coronavirus most likely came from Asian bat:
Hong Kong study
Sars-Cov-2 diverged from the most closely related known (Chinese) bat virus
50 years ago.
An "Economist" article speculates that it may have evolved in Vietnamese bats.
Vietnam has relatively few reported COVID-19 cases, and speculation has Sars-Cov-2
and related viruses circulating long enough for Vietnamese to have developed immunity,
which generally had not happened among Chinese or elsewhere.
Lots of states - such as Florida, California, and New York - have mishandled
the pandemic since it hit in March. But when you look closely at Georgia,
you see a state with a leader unique among his peers.
First-term Republican Governor Brian Kemp is a wannabe authoritarian,
and millions of Georgians have suffered as a result,
with no end in sight.
European nations still lead the world in COVID-19 deaths per capita.
Public health officials around the world excluded nursing homes
from their pandemic preparedness plans and omitted residents
from the mathematical models used to guide their responses.
https://www.aier.org/article/the-real-pandemic-was-a-nursing-home-problem/
The South Carolina Department of Health and Environmental Control (DHEC)
today announced its new
"Fight the Spread" campaign
The Gates Foundation is handing $150M to the Serum Institute,
the largest manufacturer of vaccines globally by volume,
to produce 100 million doses that would cost at most just $3 each
for vaccines being pursued by AstraZeneca and Novavax.
"Those are the ones most scalable and low-cost."
Fauci: chance of coronavirus vaccine being highly effective (>=98%) is
'not great'
Scientists are hoping for a coronavirus vaccine that is at least 75% effective,
but 50% or 60% effective would be acceptable, too, he said.
"You've got to think of the vaccine as a tool to be able
to get the pandemic to no longer be a pandemic, but to be something that's well controlled,"
The FDA has said
it would authorize a coronavirus vaccine so long as it is safe and at least 50% effective.
A single molecular descriptor to predict solution behavior of therapeutic antibodies
This is basically a pharmaceutical engineering paper which points out that, despite
growing success of monoclonal antibodies (mAbs), they too often have "poor solution behavior",
which maps to intravenous infusion administration of mAbs mainly restricted to hospital settings.
This paper promotes greater consideration of solubility early in mAbs identification
https://advances.sciencemag.org/content/6/32/eabb0372
.. specifically proposing the use of diffusion interaction parameter,
described as dilute-solution measure of colloidal self-interaction, as a metric.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388210/
A new proof-of-concept study by researchers at the University of Chicago and Duke University
showed that self-assembling peptide nanofibers tagged with antigens
can induce an immune response and activate T cells
without the use of additional adjuvants, which can induce inflammation
and are associated with common vaccine side effects,
like soreness at the injection site or low-grade fever.
https://advances.sciencemag.org/content/6/32/eaba0995
Low-cost measurement of facemask efficacy
proof-of-concept setup consisted of a box, a laser, a lens, and a cell phone camera
The best face coverings were N95 masks without valves
- the hospital-grade coverings that are used by front-line health care workers.
Surgical or polypropylene masks also performed well.
But hand-made cotton face coverings provided good coverage,
eliminating a substantial amount of the spray from normal speech.
On the other hand, bandanas and neck fleeces such as balaclavas
didn't block the droplets much at all.
"The notion that 'anything is better than nothing' didn't hold true."
https://www.medrxiv.org/content/10.1101/2020.06.19.20132969v1.full.pdf
How to fix the COVID-19 dumpster fire in the U.S.
Embrace al fresco living but tailor tools to local settings
Teach people to think in terms of harm reduction
Accept that for now the virus has the upper hand
Mine the data more efficiently
Cut out the politics
Provide more help for the hardest hit
Pop-up testing sites
Daily home testing, on Uncle Sam
Contact tracing, with national support
https://www.statnews.com/2020/07/14/fix-covid-19-dumpster-fire-us/
The website
Covidexitstrategy.org has updated its previously tri-colored U.S. map,
which showed states as either green, signifying they are trending better;
yellow, making progress; or red, trending poorly. A fourth designation,
called "bruised red", signals states with uncontrolled spread; criteria for this category
includes hospitals nearing capacity both in terms of overall beds and ICU space.
Already 17 states are wearing bruised red.
https://www.covidexitstrategy.org/
COVID-19: Immune system gone astray
Contrary to what has been generally assumed so far,
a severe course of COVID-19 does not solely result in a strong immune reaction
- rather, the immune response is caught in a continuous loop of activation and inhibition.
"Here, neutrophils and monocytes are only partially activated and they do not function properly.
We find considerably more immature cells that have a rather inhibitory effect on the immune
response. The phenomenon can also be observed in other severe infections,
although the reason for this is unclear. Many indications suggest that the immune system
stands in its own way during severe courses of COVID-19. This could possibly lead to
an insufficient immune response against the corona virus,
with a simultaneous severe inflammation in the lung tissue."
https://medicalxpress.com/news/2020-08-covid-immune-astray.html
https://www.cell.com/cell/pdf/S0092-8674(20)30992-2.pdf
Credible assumptions replace missing data in COVID analysis
Using a technique called "partial identification," researchers concluded that
actual cumulative rates of COVID-19 infection are higher than reported rates of infection,
and therefore actual infection fatality rates are lower than reported rates.
They assumed that
infection rate among those tested is higher than the rate among those who are not,
and some persons tested were actually positive but not counted (false negatives).
"The bounds you get are wide, but they are substantially tighter
compared to the bounds you obtain if you assume nothing about the missing data."
https://www.sciencedirect.com/science/article/pii/S0304407620301676
A new open-source coronavirus simulation,
released to help authorities forecast the effects of local lockdown measures,
has predicted that a second wave of COVID 19 is probable in 'almost all cases'
across the London Boroughs for which it has been run,
although the outbreak is likely to be significantly less severe than the first.
"Our simulations allow authorities to see the impact of things like closing a local supermarket,
or changing the constraints placed on schools or businesses at a very local level."
The simulation was validated up to 80 days using anonymised data
supplied by the London North West University Healthcare NHS Trust
and contains a "very wide range of local intervention types"
- from shutting pubs or limiting access to parks,
to closing certain businesses or restricting individual households -
to help local authorities plan lock-down measures.
"We hope that others can take the codes and model their local areas
- so councils could do that or even local volunteers,
to get an idea of how COVID-19 is spreading in their local community.
It probably can't be set up by a complete layman,
but people familiar with building simulations could do it."
https://github.com/djgroen/facs
https://bura.brunel.ac.uk/bitstream/2438/20914/4/FullText.pdf
https://medicalxpress.com/news/2020-08-localised-coronavirus-simulations-cases.html
UK Researchers have identified a pattern of longer-term symptoms
likely to be experienced by people who were hospitalized with the COVID-19 infection.
"The emerging evidence is that for some, the road to recovery may take months
and it is vital specialist rehabilitation is on hand to support them."
More than 60% of people who had been treated on a ward reported fatigue,
and one-third of them described it as moderate or severe.
For patients who had been in intensive care, 72% reported fatigue.
The second most common symptom was feelings of breathlessness
which had not existed before they contracted COVID-19,
reported by 65.6% of ICU vs. 42.6% of other patients.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26368
COVID-19 transmission within U.S. families.
Pulled from participants in previous government research,
some 2,000 families in 11 U.S. cities are enrolled in a DIY COVID-19 experiment.
They collect their own nasal swabs, and less often blood and stool samples,
mailing specimens to the study organizers. Participants get text messages
asking about symptoms and reminding them to test and they fill out questionnaires.
https://medicalxpress.com/news/2020-08-kids-parents-diy-coronavirus-science.html
"Masks can prevent many infections altogether,
as was seen in health care workers when we moved to universal masking.
We're also saying that masks, which filter out a majority of viral particles,
can lead to a less severe infection if you do get one."
https://link.springer.com/article/10.1007/s11606-020-06067-8
The Pennsylvania Health Department last week canceled a training session
for coronavirus contact tracing volunteers, saying,
"August is usually a month filled with families taking time for a vacation."
Then, the next day, it announced
a $23 million plan to hire 1,000 contact tracers.
Nearly every country has struggled to contain the coronavirus,
but only one affluent nation has suffered a severe, sustained outbreak for more than four months: the U.S..
An aversion to collective action helped lead to inadequate state lockdowns
and inconsistent adherence to mask wearing based on partisanship instead of public health.
"If you had to summarize our approach, it's really poor federal leadership - disorganization
and denial," said Andy Slavitt, who ran Medicare and Medicaid from 2015 to 2017.
"This isn't actually rocket science. We know what to do, and we're not doing it."
https://www.techmaq.com/america-stands-alone/
Tiny Texas company eTrueNorth runs most of the drive-thru COVID-19 testing in the U.S.
The company has brought in more than $90 million in federal contracts
to help oversee more than 350 sites and pay for the tests.
For eTrueNorth to sign a contract with the Department of Health and Human Services,
it needed to find CLIA-certified labs that would run whatever tests they collected.
Eventually, it found three: HealthQuest Esoterics in California,
Gravity Diagnostics in Kentucky, and Reditus Laboratories near Peoria, Ill.
However, the federal government's community-based testing sites account for
a remarkably small proportion of the country's daily count.
By July 24, about 1.1 million people had been tested over three months through the CBTS program.
https://www.statnews.com/2020/08/03/etruenorth-tiny-company-running-covid-19-company/
Color's LAMP-based tests improve sensitivity by extracting and purifying
RNA on a particular machine that uses magnetic beads, concentrating the RNA.
Replicating Color's automation would require about $500,000 worth of equipment,
according to Chris Mason, a computational genomics specialist at Weill Cornell Medicine.
https://www.statnews.com/2020/08/06/better-simpler-faster-covid-19-test/
An Associated Press analysis found that the number of tests per day slid 3.6%
over the past two weeks to 750,000, with counts falling in 22 states.
"If people have something to do on a Saturday and they want to get tested,
they're not going to wait for two hours in the South Carolina heat for a test,
especially if they're not symptomatic"
https://www.pressreader.com/usa/chicago-tribune/20200806/281672552288125
The primary way COVID-19 is transmitted is through respiratory droplets
that careen through the air, and yet the capricious nature of air circulation and
the lack of filtration systems in public school systems is absent from the conversation.
If we're not willing or able to fund essential upgrades to school ventilation systems,
let's admit that.
https://www.statnews.com/2020/08/05/ventilation-part-of-school-reopening-conversation/
During initial isolation of 13 individuals with COVID-19 at the University of Nebraska Medical Center,
viral contamination was detected among all air and surface samples collected,
supporting the use of airborne isolation precautions when caring for COVID-19 patients.
https://www.nature.com/articles/s41598-020-69286-3
Purdue University innovators have developed an airborne disinfection method
using food-coloring dyes to be applied to the entire body and rooms
for sterilization purposes and lowering the risk of infection.
This is referred to as Photodynamic Airborne Cleaner (PAC).
"Most of the antiviral and antibacterial sprays used for airborne antiviral and antibacterial disinfectants,
such as aerosolized hydrogen peroxide, ozone and deep ultraviolet illumination,
are a biohazard risk to humans."
https://www.eurekalert.org/pub_releases/2020-08/pu-nat080520.php
Structure-Based Design of UCI-1 a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease
UCI-1 is ring-shaped molecule called a macrocycle
that's designed to block an enzyme essential to SARS-CoV-2 reproducion.
https://www.biorxiv.org/content/10.1101/2020.08.03.234872v2
University of Michigan medicinal chemists have used artificial intelligence
to find alternative pharmaceutical building blocks for 12 drugs under investigation to treat COVID-19.
Those drugs include bromhexine, camostat, cobicistat, darunavir, favipiravir, galidesivir, nelfinavir,
ritonavir, umifenovir, ribavirin, remdesivir and baricitinib.
"The route we have found for some of these potential therapeutics might be longer than what's out there,
but in most cases, such as umfenovir, we're actually finding routes that are shorter
and starting materials that are cheaper than what's currently available.
We found a way to make the therapeutic bromhexine in one-step, which we are pretty stoked on."
4.2 billion vaccine doses are needed for essential workers, the sick and elderly.
https://phys.org/news/2020-04-reactions-molecular-properties.html
To guarantee 100 million doses, the U.S. government Wednesday announced a new
$1 billion investment
in Johnson & Johnson's Ad26.COV2.S COVID-19 vaccine, which had already received $456 million
in March via its Janssen subsidiary. The new money will fund production ramp up
so that doses are ready for shipping if and when their drug receives regulatory approval.
Scientists from MedUni Vienna's Institute of Pathophysiology and Allergy Research
discovered that only around 60% of patients who have had COVID-19
and recovered from it develop protective antibodies and, for the first time,
showed that some antibodies even assist the virus by augmenting it to the cells of the host.
https://onlinelibrary.wiley.com/doi/abs/10.1111/all.14523
"Drugs that target the virus or suppress inflammatory immune responses have produced
inconsistent results and might not be the best treatment for patients with COVID-19.
Instead, the use of drugs that modulate inflammation without compromising
the adaptive immune response could be the most effective therapeutic strategy."
https://www.jimmunol.org/content/205/1/12
If the U.S. had introduced a uniform national mask mandate
for employees of public-facing businesses on April 1,
the number of deaths in the U.S. would likely have been 40% lower on June 1.
https://www.medrxiv.org/content/10.1101/2020.05.27.20115139v5
"We think if we can make our immune systems stronger,
we'll be better able to fight off this coronavirus,
as well as other viral and bacterial pathogens that may be unleashed in the future."
https://insight.jci.org/articles/view/140329
Data show significant variability in genetic determinants of ACE2 and TMPRSS2 expression
among individuals and between populations, and indicate variability in disease susceptibility
and severity of COVID-19 depending on patients' genetics.
https://www.nature.com/articles/s41435-020-0107-7
Method for screening poor-performing commercial masks and respirators
Currently the certification capacity of NIOSH is too limited to accommodate
the high demand for testing of masks and allow for timely decision making on purchases
or the use of donated masks during this critical nationwide shortage.
https://www.nature.com/articles/s41370-020-0258-7
Honeysuckle decoction HD has been used to treat viral infections for a thousand years in China.
Results suggest that absorbed plant microRNA, MIR2911, which is enriched in HD
inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients.
https://www.nature.com/articles/s41421-020-00197-3
A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2
An experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs)
provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection
and for disease modeling of COVID-19
Although human coronaviruses previously had not been considered to infect liver cells,
our results are consistent with current COVID-19 clinical observations
that more than 50% of patients have evidence of viral hepatitis.
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30282-4
Sites of vulnerability in SARS-CoV-2
Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients.
A subset of antibodies was able to neutralize the virus.
Competition and electron microscopy studies showed that these antibodies target diverse epitopes on the spike,
with the two most potent targeting the domain that binds the host receptor.
A total of 84 mAbs that showed high-affinity binding were selected
for small-scale expression in HEK 293F cells and purified.
A total of 19 mAbs (23%) inhibited SARS-CoV-2 pseudovirus infection with varying potencies
and, of these, 14 (74%) bound the RBD. Seven of the 19 mAbs could be categorized as
potent neutralizing antibodies (NAbs),including the most potent NAbs: COVA1-18 and COVA2-15
https://science.sciencemag.org/content/369/6504/650
Broad neutralization of SARS-related viruses by human monoclonal antibodies
Wec et al. isolated and characterized hundreds of antibodies
against the viral spike protein of SARS-CoV-2
from the memory B cells of a survivor of the 2003 outbreak caused by the related coronavirus, SARS-CoV.
Of nine antibodies that showed strong cross-neutralization,
eight targeted the domain that binds to ACE2.
These eight antibodies also neutralized a bat SARS-related virus.
https://science.sciencemag.org/content/369/6504/731
6-7 states conspire with Rockefeller Foundation for rapid point-of-care COVID-19 antigen tests
Maryland Governor Larry Hogan, Louisiana Governor John Bel Edwards, Massachusetts
Governor Charlie Baker, Michigan Governor Gretchen Whitmer, Ohio Governor Mike DeWine,
and Virginia Governor Ralph Northam are in discussions with Becton Dickinson and Quidel
- U.S. manufacturers of antigen tests that have already been authorized by the FDA -
to purchase 500,000 tests per state, for a total of three million tests.
"I'm hopeful that the president and Congress will follow our lead and work together on a recovery
package that includes support for states like ours so we can continue to protect our families."
NC Governor Roy Cooper announced his intent to join the interstate compact.
Clinical trials of monoclonal antibodies, which could both prevent and treat COVID-19,
are underway and could produce signs of efficacy in the next few months,
perhaps ahead of vaccine trials. On 15 July, Lilly, AbCellera, AstraZeneca, GlaxoSmithKline,
Genentech, and Amgen jointly asked the U.S. Department of Justice (DOJ) whether they
could share information about manufacturing their monoclonals without violating antitrust laws,
"to expand and expedite production."
https://www.sciencemag.org/news/2020/08/designer-antibodies-could-battle-covid-19-vaccines-arrive
Lyme disease shares a number of symptoms with COVID-19, including fever, achiness and chills.
If Lyme disease is identified and treated quickly,
then 2-4 weeks of antibiotics usually knock out Borrelia burgdorferi bacteria that cause it,
else neurological and cognitive problems and potentially fatal heart problems can develop,
and painful arthritis that is much more difficult to treat can set in.
[Another "decoy" for SARS-CoV-2]:
Engineering human ACE2 mutations to optimize SARS-CoV-2 binding
Since human ACE2 has not evolved to recognize SARS-CoV-2 S,
researchers hypothesized that mutations may be found that increase affinity.
The efficacy of monomeric sACE2.v2.4 to neutralize SARS-CoV-2 infection
of cultured VeroE6 cells exceeded the wild type protein by nearly two orders of magnitude,
consistent with biochemical binding data.
https://science.sciencemag.org/content/early/2020/08/03/science.abc0870
[ much as cowpox produces smallpox immunity,
perhaps common cold coronaviruses produce COVID-19 resistance ]
A range of pre-existing memory CD4+ T cells are demonstrated to be cross-reactive
with comparable affinity to SARS-CoV-2
and common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1.
These finding of cross-reactive HCoV T cell specificities
are stark contrast to HCoV neutralizing antibodies, which are HCoV species-specific
and did not show cross-reactivity against SARS-CoV-2 receptor-binding domain.
https://science.sciencemag.org/content/early/2020/08/04/science.abd3871
CDC: A new outbreak of acute flaccid myelitis, a potentially fatal polio-like illness,
could strike hundreds of American children within the next few months.
The disease is thought to be caused by a respiratory virus called an enterovirus,
which in the vast majority of cases causes mild symptoms.
https://www.cdc.gov/acute-flaccid-myelitis/index.html
Photodynamic therapy, which combines light and a photosensitizing chemical substance
to kill microorganisms in the respiratory tract, is advocated as a complementary treatment
for secondary infections in COVID-19 patients.
https://www.sciencedirect.com/science/article/pii/S1572100020301587
ACTIV-2, a NIH phase 2 trial to test antibodies and other therapeutics
for mild, moderate COVID-19. The trial will be led by the National Institute
of Allergy and Infectious Diseases (NIAID)-funded AIDS Clinical Trials Group (ACTG).
ACTIV-2 was established as part of NIH's
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV),
a public-private partnership program.
The first therapeutic to be tested in this trial will be Eli Lilly's LY-CoV555.
https://medicalxpress.com/news/2020-08-nih-trial-antibodies-therapeutics-mild.html
Testing, contact tracing and household quarantine impacts on COVID-19 second wave,
based on a detailed agent-based Boston metropolitan area transmission model.
https://www.nature.com/articles/s41562-020-0931-9
state officials are already confused about plans to distribute a vaccine when one exists
With the Trump administration aiming to deliver 300 million doses of vaccine
against the coronavirus as early as January, state officials and health experts say
they remain in the dark about key details and, therefore, are inadequately prepared
for what is expected to be the largest single vaccination campaign ever undertaken.
"It's probably the hardest thing they're going to do," Paul A. Offit,
director of the Vaccine Education Center at Children's Hospital of Philadelphia
and a member of a federal vaccine advisory group.
At a recent briefing for the advisory group by Operation Warp Speed,
the administration's effort to fast-track development of coronavirus countermeasures,
Lt. Gen. Paul Ostrowski, who oversees logistics, said
the military would move vaccines onto trucks for distribution "the day after"
the drugs received regulatory approval from the FDA, Offit recalled.
But Offit said that, based on the administration's inability to
develop a national testing strategy,
secure adequate supplies of personal protective equipment, and
deliver a consistent message about wearing face masks,
the question he wanted to ask Ostrowski but didn't have the chance was basic:
"Given that the administration efforts have largely been failures,
what makes you think this will work?"
The administration already botched a rollout of remdesivir,
one of the only approved COVID-19 treatments.
https://www.washingtonpost.com/health/2020/05/28/remdesivir-coronavirus-trump/
To stop outbreaks from overwhelming communities,
"we need fast, frequent testing"
If administered properly, PCA tests are highly accurate,
spotting positive cases nearly 100% of the time.
That accuracy is vital for decisions about treating individual patients.
But PCR tests cost about $100 each, require specialized machinery and reagents, but
typically return results at least 1 to 2 days and currently 2 weeks later in some places.
FDA authorizes Siemens' fully automated chemiluminescent immunoassays,
ADVIA Centaur COV2G and Atellica IM COV2G,
as first tests to estimate serum coronavirus antibody counts, instead of just yes/no results.
"Being able to measure a patient's relative level of antibodies in response
to a previous SARS-CoV-2 infection may be useful as we continue to learn more
about the virus and what the existence of antibodies may mean"
NIH picks seven COVID-19 diagnostic tests in Rapid Acceleration of Diagnostics initiative
(RADx) 'Shark Tank' competition,
unlocking $248.7M in scale-up funding
Three focus on providing in-person results in under a half-hour:
* Mesa Biotech's hand-held Accula test, with a single-use, RT-PCR cartridge;
* Quidel's Sofia antigen test kit, as an electronic, lateral flow immunoassay;
* Talis Biomedical's Talis One viral RNA loop-mediated isothermal amplification (LAMP) test
The other four are for labs:
* Ginkgo Bioworks' aims for 50K (in Sep) and 100K (in Dec) tests per day
* Helix OpCo plans to ship bulk, standardized nasal swab collection kits
* Fluidigm will primarily focus on saliva-based samples, using its microfluidic chip platform
* Mammoth Biosciences looks to replace PCR with simpler faster CRISPR lab test
SARS-CoV-2, but not SARS-CoV, infects human neural progenitor cells.
Susceptibility of human brain organoid was similarly suggested by two independent studies.
However, permissiveness of neuronal progenitor cells to SARS-CoV-2
was not evaluated in these studies and may impair recovery of the olfactory function
and other neurological manifestations.
https://www.nature.com/articles/s41422-020-0390-x
South Korea's Macrogen has received a CE mark for a new coronavirus test kit,
Axen COVID-19 RT. The test confirms if a patient is infected with the virus
in approximately two hours through detection of two COVID-19-related genes
with 100% accuracy in 20 samples each of positive and negative patients in a clinical trial.
It is currently awaiting a decision by the FDA for an Emergency Use Authorization.
One of the immune system's oldest branches, called complement,
may be influencing the severity of COVID-19 disease,
according to researchers at Columbia University Irving Medical Center.
Among other findings linking complement to COVID-19,
people with age-related macular degeneration
- a disorder caused by overactive complement -
are at greater risk of developing severe complications and dying from COVID.
Existing drugs that inhibit the complement system could help treat patients.
https://www.nature.com/articles/s41591-020-1021-2
progress
The U.S. recorded more than 1.9 million new COVID-19 infections in July,
nearly 42% of the more than 4.5 million cases reported nationwide since the pandemic began
and more than double the number documented in any prior month
https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html
Birx: "What we are seeing today is different from March and April.
It is extraordinarily widespread. It's into the rural as equal urban areas"
The U.S. added 47,508 COVID-19 cases Sunday.
The previous five days had each recorded more than 60,000 new infections.
Florida has the second-highest caseload of all states except California,
which has double the population.
https://medicalxpress.com/news/2020-08-covid-cases-hours.html
Kodak's COVID-19 hanky panky
Executive chairman Jim Continenza gets a windfall based on an 'understanding';
previously undisclosed options grant shields him from convertible bond dilution.
Prior to this week, Kodak warned investors it was at risk of not continuing as a going concern,
but it was boosted Tuesday by Trump's $765 million deal for drug ingredients.
The decision to grant Continenza options was never formalized
or made into a binding agreement,
which is why it was not disclosed previously...
Critically ill COVID-19 patients recovered rapidly from respiratory distress
after treatment with RLF-100, two drug companies said.
In the U.S., RLF-100 has been granted fast track designation by FDA
for treatment of respiratory distress in COVID-19.
While a Phase 2/3 clinical trial with 70 patients is ongoing,
RLF-100 is being administered on an emergency basis
to some patients who are too ill to be admitted to the trial.
The first report of rapid recovery under emergency use was posted
by doctors from Houston Methodist Hospital, the companies said in a joint statement.
Geneva-based Relief Therapeutics Holdings AG RFLB.S has a patent for RLF-100,
or aviptadil, a synthetic form of a natural peptide for erectile dysfunction.
U.S.-Israeli NeuroRx Inc partnered with Relief to develop the drug in the U.S..
Merck to start 2 large phase 3 trials of controversial remdesivir alternative in September,
without disclosing any results from previous phases of human trials.
Some studies suggested oral antiviral MK-4482, formerly known as EIDD-2801,
could cause harmful mutations.
After filing a whistleblower complaint about it,
Biomedical Advanced Research and Development Authority (BARDA) head
Rick Bright was dismissed in mid-April.
https://en.wikipedia.org/wiki/MK-4482
Mandated BCG vaccination can be effective against COVID-19.
Bacillus Calmette-Guerin (BCG) vaccination (typically given at birth and/or during childhood)
reduces tuberculosis risk by 50%. Recent experimental work finds that
BCG vaccination causes genome-wide epigenetic reprogramming of human monocytes.
A model estimates that the total number of COVID-19 related deaths in the U.S.
as of March 29, 2020 would have been 468 - 19% of the actual figure (2467) -
if the U.S. had instituted the mandatory BCG vaccination several decades earlier
https://advances.sciencemag.org/content/early/2020/07/30/sciadv.abc1463
Potential COVID-19antiviral drug development
This review highlights recent research in the structure, function and development
of antiviral drugs targeting the spike (S) protein of SARS-CoV-2 [a],
which plays a key role in the receptor recognition and cell membrane fusion process,
and is composed of two subunits, S1 and S2 [b-c].
The S1 subunit contains a receptor-binding domain
that recognizes and binds to the host receptor angiotensin-converting enzyme 2 [d],
while the S2 subunit mediates viral cell membrane fusion
by forming a six-helical bundle via the two-heptad repeat domain [e].
a: Potential mAbs targeting various epitopes of the S protein
b: Summary of current SARS-CoV-2 inhibitors
https://www.nature.com/articles/s41401-020-0485-4
Russian Health Ministry plans mass coronavirus vaccination starting in October
"Closer to the end of the year and the start of next year we can talk about
switching to a vaccination at least for people from risk groups
with a further switch to massive vaccination"
https://tass.com/coronavirus-outbreak-in-china/1184789
Combining in situ measurements and computational fluid dynamics simulations,
engineers quantify particles exhaled by normal respiratory behaviors
and their transport under elevator, small classroom, and supermarket settings
to evaluate the risk of inhaling potentially virus-containing particles.
Only 10% of aerosols were filtered out in a simulation
where an asymptomatic teacher talked for 50 minutes straight.
"Because this is very strong ventilation, we thought it would ventilate out a lot of aerosols.
But 10% is really a small number... they are basically trapped in this vortex,
and it's very hard for them to reach the vent and actually go out."
Aerosols spread significantly less throughout the space
when the teacher was placed directly under an air vent.
https://arxiv.org/ftp/arxiv/papers/2007/2007.03645.pdf
In a database of more than 1,200 super-spreader events,
just one incident is classified as outdoor transmission
(where a single person was infected outdoors by their jogging partner),
and only 39 are classified as outdoor/indoor events
(which doesn't mean that being outdoors played a role, but it couldn't be ruled out).
The rest were all indoor events, and many involved dozens or hundreds of people at once.
Other research points to the same result:
Super-spreader events occur overwhelmingly at indoor environments where there are a lot of people.
https://superspreadingeventsdatabase.blogspot.com/p/about.html
[
basically a rewrite of June 30 news ]
Cancer is essentially a malfunctioning of cellular machinery that causes runaway cell growth.
Viruses also change the function of cellular machinery, but instead of causing cell growth,
machinery is repurposed to reproduce viruses, taking control over many kinases to do this.
Among the better understood 97 of 518 human kinases, the virus was found to affect 49.
87 existing drugs were found to change kinase-controlled pathways used by SARS-CoV-2
Of 68 drugs tested, several effectively killed the virus in cells, and
silmitasertib, gilteritinib, ralimetinib, apilimod and dinaciclib are either approved,
in clinical testing or under preclinical development for treatment of various diseases.
Genomic survey of multiple SARS-CoV-2 introductions into Northern California
Northern California experienced a complex series of introductions of the virus, deriving
not only from state-to-state transmission but also from international travel by air and ship.
Georgia proves COVID-19 contagion among youths
A total of 597 Georgia residents attended an overnight camp in Georgia June 17-20.
Median camper age was 12 years (range = 6-19 years), and 53% (182 of 346) were female.
The median age of staff members and trainees was 17 years (range = 14-59 years),
and 59% (148 of 251) were female. Test results were available for 344 (58%) attendees;
among these, 260 (76%) were positive. The overall attack rate was 44% (260 of 597),
51% among those aged 6-10 years, 44% among those aged 11-17 years,
and 33% among those aged 18-21 years.
Attack rates increased with increasing length of time spent at the camp,
with staff members having the highest attack rate (56%). During June 21-27,
occupancy of the 31 cabins averaged 15 persons per cabin (range = 1-26);
median cabin attack rate was 50% (range = 22%-70%)
among 28 cabins that had one or more cases.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6931e1.htm?s_cid=mm6931e1_w
Bill Gates: antiviral drugs, monoclonal antibodies, and steroids are all promising treatments
that could be ready to go much sooner than vaccines, possibly by the end of 2020.
"You can see the therapeutic benefit faster than the protective benefit," Gates said.
"So I think there's a good chance we'll have substantial death-rate reduction
by the end of the year with the combination of those new tools."
https://www.cnbc.com/2020/07/28/coronavirus-live-updates.html#106635376-pSNACmsky
Given the attack rates estimated for train passengers in the same row as an index patient,
a safe social distance of more than one meter is required for one hour spent traveling together;
after two hours, less than 2.5 meters may be insufficient to prevent transmission.
https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1057/5877944
Members of Jared Kushner's coronavirus task force may have believed the pandemic
would affect Democratic areas worse and
recommended against federal response.
How does SARS-CoV-2 cause COVID-19?
Understanding the cellular basis of SARS-CoV-2 infection could reveal treatments
that prevent development of severe disease. [but may provoke headaches]
https://science.sciencemag.org/content/369/6503/510
The number of new coronavirus cases in the U.S. shot up by over 20% per week for the past month.
This week, it rose by a comparatively modest 7%. That doesn't mean we're getting better.
The U.S. may be leveling off, but it's leveling off at a very high rate of infection.
The country is averaging roughly 66,000 new cases per day.
[
includes color-coded interactive state map of trends ]
DARPA takes credit for Inovio and Moderna vaccines
"Skeptics cited the lack of evidence that it would work,
and Dan cited the lack of evidence that it wouldn't," Dugan recalled.
"That's very typical of a DARPA program." [ there is no substitute for cubic dollars ]
[ How does U.S. DoD fund R∓D @ Vancouver, Canada-based firm AbCellera? ]
Why Australia's second outbreak is different
This outbreak is blamed on improperly trained private security forces at quarantine hotels,
where people who fly into Australia must stay for two weeks under mandatory quarantine,
with allegations of shared cigarette lighters and sex with quarantined travelers.
https://www.bbc.com/news/world-australia-53259356
Johnson & Johnson announced July 30 that a single shot of vaccine candidate
Ad26.COV2-S produced a "robust immune response" to SARS-CoV-2 in rhesus macaques.
"The findings give us confidence as we progress our vaccine development and upscale manufacturing in parallel,
having initiated a Phase I/IIa trial in July with the intention to move into
a Phase III trial in September."
Dr. Elizabeth Nabel, president of Brigham and Women's Hospital,
has resigned from Moderna's board of directors, in a futile gesture
to address a "
potential or even apparent conflict of interest"
arising from that hospital's participation in Moderna's phase three vaccine trial.
FDA EUA for Truvian Sciences' Easy Check, a $15 portable serum antibody test
for use by health professionals with an accuracy rate in excess of 98%.
https://truvianhealth.com/archives/press/072920
Pharmacological inhibition of viral enzyme PLpro not only blocks SARS-CoV-2 replication
but also strengthens the anti-viral immune response at the same time.
https://www.researchsquare.com/article/rs-27134/v1
Roche remains committed to continuing the Actemra/RoActemra COVID-19
clinical trial programme despite showing no benefit for hospitalized COVID-19 patients in a phase 3 trial.
"People around the world are waiting for further effective treatment options for COVID-19
and we are disappointed that COVACTA did not demonstrate a benefit for patients
in either clinical status or mortality at week four."
https://www.roche.com/media/releases/med-cor-2020-07-29.htm
"Integrating IAQ control strategies to reduce the risk of asymptomatic SARS CoV-2 infections
in classrooms and open plan offices." three-step plan:
"To reduce the number of virus-containing aerosols emitted to the space
from any possible virus carriers present, universal face masking,
as well as hand sanitizing before entering the space is essential."
"Mechanically ventilated classrooms and offices typically have
about 20% of their air supplied from outdoors, and the rest is recirculated air...
the outdoor ventilation rate should be increased to the maximum operational capacity
of the building ventilation system, which can be two or more times of that
under the normal operation mode per the existing standard."
At the building level, high efficiency particulate (HEPA) filters in recirculated
or mixed air duct can reduce cross contamination between rooms
and increase total clean air delivery rates (outdoor plus filtered air)
for diluting virus concentrations in ventilated spaces.
An air cleaner with a CADR of 722 m3/h (425 CFM) can double the clean air supply
for 25 people in a classroom or open plan office.
For a more thorough viral disinfection,
UV irradiation is recommended following the particulate air filters.
UVGI lamps create UV-C energy at a near optimum 254nm wavelength
for virus deactivation (ASHRAE 2020).
University of Texas at Austin scientists are hoping their novel
thin-film-freezing technology to deliver remdesivir through dry powder inhalation
will make treatment more potent, easier to administer and more broadly available.
https://www.biorxiv.org/content/10.1101/2020.07.26.222109v1
Detecting SARS-CoV-2 in nasal swabs using matrix-assisted laser desorption/ionization
mass spectrometry (MALDI-MS) and machine learning analysis. For 362 samples
(211 SARS-CoV-2-positive and 151 negative by RT-PCR), a support vector machine model
provided the highest accuracy (93.9%), with 7% false positives and 5% false negatives.
Although molecular techniques are undoubtedly useful for SARS-CoV-2 detection,
MALDI-MS with ML is a promising alternative given its speed, simplicity and low cost,
and equipment and expertise available in hospital laboratories in developing countries.
https://www.nature.com/articles/s41587-020-0644-7
Widespread thromboses and disseminated intravascular coagulation (DIC) are reported in COVID-19 patients.
Key features of this disorder include a lack of bleeding risk,
only mildly low platelet counts, elevated plasma fibrinogen levels,
and detection of both SARS-CoV-2 and complement components in regions of thrombotic microangiopathy (TMA).
This disorder is not typical DIC and might be more similar to complement-mediated TMA syndromes,
which are well known to rheumatologists who care for patients
with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome.
This perspective has critical implications for treatment. Standard treatments for DIC
are gravely insufficient for any of the TMA disorders that involve disorders of complement.
https://www.nature.com/articles/s41584-020-0474-5
National Academies of Sciences, Engineering and Medicine
published a guide
that is intended to help officials nationwide make sense of different COVID-19 data sources
when making public health decisions.
"Interventional COVID-19 Response Forecasting in Local Communities Using Neural Domain Adaption Models"
algorithm based on a deep learning modelcalled Transformer
"compares the growth curves of COVID-19 cases across different regions
over a period of time to determine the most-similar regions.
It then weighs these regions to forecast cases in the target region."
https://www.news.ucsb.edu/2020/019983/ai-localizes-covid-19-forecasts
PerkinElmer pooling strategy for mass population screening of SARS-CoV-2
This study analyzed 1000 samples in a pooled approach using only two-extraction and -PCR runs and achieved 91.6% PPA and 100% NPA.
The number of samples pooled are inversely proportional to analytical sensitivity of the assay and the local positivity rate.
https://jmd.amjpathol.org/article/S1525-1578(20)30407-4/fulltext
TScan Announces Discovery of Precise T Cell Targets in COVID-19 Convalescent Patients
to Inform Development of Next-generation Vaccines and T Cell-based Diagnostics.
Data show T cells recognize a small set of immunodominant epitopes
shared among patients and predominantly located outside the spike protein.
https://www.medrxiv.org/content/10.1101/2020.07.24.20161653v2
Sorrento Therapeutics has picked up a
saliva-based coronavirus test
developed by fertility researchers at Columbia University
that aims to provide an easy-to-read result in less than 30 minutes.
The entirety of the single-step test, to be dubbed COVI-TRACE,
is contained within a small tube - requiring no laboratory equipment for use just about anywhere.
How effective does a coronavirus vaccine need to be?
That depends on how many take it; 60% vaccine effectiveness would suffice if all took it.
100% effectiveness would NOT suffice
if only 50% are vaccinated.
Using influenza surveillance networks to estimate state-specific prevalence of SARS-CoV-2
Silverman et al. used data collected through an existing infrastructure
for reporting influenza-like illness (ILI)
to estimate the actual prevalence of SARS-CoV-2 infections in states.
Their model estimated that more than 80% of U.S. COVID-19 infections went undetected in March 2020.
They identified excess ILI cases by first subtracting cases due to influenza
and then subtracting the seasonal signal of non-influenza ILI.
A 4-day lag between the onset of infectiousness and presentation with ILI
yields a clinical rate of 25% among the 87% of simulations,
which could account for the ILI surge.
https://stm.sciencemag.org/content/12/554/eabc1126
New evidence suggests that COVID-19 is following younger people home
from work or social outings, then infecting older and more vulnerable household members.
64 million people - about 20% of the U.S. population - lived in homes
with at least 2 adult generations or grandparents and grandchildren under 25 in 2016.
National security adviser Robert C. O'Brien probably caught the virus from his daughter.
Bruker's
FluoroType SARS-CoV-2 plus PCR assay has earned a CE Mark in Europe
for detection of COVID-19 infections, demonstrating 100% accuracy in 2 clinical trials.
SARS-CoV-2 Orf9b suppresses type I interferon (IFN-1) responses by targeting TOM70.
Considering the critical role of IFN-I in the human antiviral response,
restoration of IFN-I production in COVID-19 patients may prove to be a significantly effective therapeutic option.
https://www.nature.com/articles/s41423-020-0514-8
COVID-19 patients constantly present with severe lymphopenia.
Recombinant human interleukin-7 (IL-7) therapy is worth trying with patients based on marked lymphopenia.
https://www.nature.com/articles/s41423-020-0516-6
Among 100 adults who recently recovered from COVID,
78% showed some type of cardiac involvement in MRI scans and
60% had ongoing inflammation in the heart.
"What they're saying in this study is that you can identify myocardial involvement
or heart involvement by magnetic resonance imaging"
https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916
As Missouri topped its daily high for new COVID-19 cases Tuesday
for the ninth time this month, St. Louis County Executive Sam Page
voiced concern over
delays in testing results reaching patients and health officials.
A recombinant vaccine comprising residues 319-545 of SARS-CoV-2's Spike protein receptor-binding domain
could induce a potent functional antibody response in the immunized mice, rabbits
and non-human primates (Macaca mulatta) as early as 7 or 14 days after a single dose injection.
https://www.nature.com/articles/s41586-020-2599-8
ExeVir Bio has been established by Belgian partners to develop
Llama-derived antibody (VHH) technology,
including VHH72-Fc which binds to a unique epitope that is conserved in SARS-CoV-1 and SARS-CoV-2 viruses,
preventing them from entering cells.
The importance of this approach is that it could be used both as a therapeutic and prophylactic.
Smaller than human antibodies, VHHs can bind to otherwise inaccessible parts of the virus.
Another broad survey of known drugs identifies 13 likely COVID-19 therapies
International collaboration profiled a library approximately 12,000 clinical-stage
or FDA-approved small molecules, identifying 13 likely to be therapeutic,
including the PIKfyve kinase inhibitor apilimod,
and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334.
[ PIKfyve and ONO 5334 had been previously identified].
https://www.nature.com/articles/s41586-020-2577-1
With the coronavirus, there's no "pre-Trump normal" to go back to.
Former Vice President Joe Biden built a career on incremental change.
Now he's styling himself as the next Franklin Delano Roosevelt.
Biden's campaign was defined early on as a return to "normalcy"
- the time before President Donald Trump took office -
but now he is thinking much bigger.
https://www.vox.com/2020/7/28/21318721/coronavirus-joe-biden-trump-election
Pfizer and BioNTech announced the start of a global (except for China)
Phase 2/3 safety and efficacy
clinical study of BNT162b2 mRNA-based vaccine candidate.
Masks can mitigate risk of COVID-19 'super spreaders' in rooms
A severely infected person who's coughing frequently can fill a poorly ventilated room
with as many as 7.4 million copies of the coronavirus for every cubic meter of air.
"...individuals may be at risk of infection if they spend more than a few minutes
in a small room with a person who is infected with COVID-19..."
"Swiss researchers gathered data from a handful of prior studies that tracked
how much coronavirus the average infected person will emit by breathing normally,
as well as the virus released by a very sick person who's coughing frequently.
The team then used a mathematical model to estimate how much virus
either a low- or high-emitting patient is likely to release into the air of a closed room.
While engaged in activities like loud speaking or singing,
viral emissions can increase by 1 to 2 orders of magnitude, the researchers said.
People at rest tend to breathe in about a half a cubic meter of air every hour.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768712
Savannah, GA TV news anchor Dawn Baker is the
first person in the U.S.
to participate in Moderna's Phase 3 COVID-19 vaccine clinical trial.
There are 89 study sites across the country for this vaccine,
and Phase 3 trials are underway for four other vaccines,
three of those in China and one in the United Kingdom. [
includes U.S. map of COVID-19 cumulative cases by county ]
[ plenty more from where coronavirus came ]
Using 3 different bioinformatic approaches to identify and remove recombinant regions
within the SARS-CoV-2 genome, researchers found that,
although SARS-CoV-2 is genetically about 96% similar to the RaTG13 coronavirus,
which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China,
the team found that it diverged from RaTG13 in 1969.
"other viruses that are capable of infecting humans are circulating in horseshoe bats in China"
"SARS-CoV-2's RBD sequence has so far only been found in a few pangolin viruses.
Furthermore, the other key feature thought to be instrumental to SARS-CoV-2's ability to infect humans
- a polybasic cleavage site insertion in the Spike protein -
has not yet been seen in another close bat relative of the SARS-CoV-2 virus.
Yet, while it is possible that pangolins may have acted as an intermediate host
facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that
pangolin infection is a requirement for bat viruses to cross into humans. Instead,
our research suggests that SARS-CoV-2 likely evolved the ability
to replicate in the upper respiratory tract of both humans and pangolins."
https://www.nature.com/articles/s41564-020-0771-4
A 3-D visualisation of simple hygiene: Soap vs COVID-19
A scientifically accurate simulation, a collaboration between UNSW Art & Design and UNSW Science,
shows
soap acting on contaminated skin covered with tiny coronavirus particles.
Two classic hayfever symptoms can help
distinguish allergies and virus infections.
1) Hayfever, despite its name, does not cause increased body temperature.
Flu-like illnesses do cause fever, and sore muscles (myalgia), malaise and fatigue.
2) If nasal symptoms improve with antihistamine medication, then allergy or hayfever is likely.
Antihistamines do not alleviate symptoms of the common cold.
A team of
health economists from U.S. universities estimate that by the end of 2020,
public health measures to mitigate COVID-19, including shelter-in-place orders,
school and business closures, social distancing and face mask recommendations,
would save between 900,000 and 2.7 million lives in the U.S.
The economic downturn and loss of income from shelter-in-place measures
and other restrictions on economic activity could contribute to between 50,400 and 323,000 deaths,
based on an economic decline of 8%-14%.
"What we already know is vaccination often involves polarizing the immune system
towards the type of immune response believed to provide protection to a given infection
and away from responses believed to be non-protective.
What we have realized through our research is that
types of immunity that we didn't think were important, or were thought to be non-protective,
are actually critical to regulate the protective cell-mediated response
to ensure the immune system mounts a balanced defense."
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30175-X
Minnesota and Ohio became the latest states to mandate face masks
in all businesses, stores and indoor public spaces where people gather.
"States that put in mandates saw a 2% drop, per day, in the number of cases occurring.
Now that 2% might not sound big, but when you look at that as a whole,
that means that intervention alone has about a 20% effect in decreasing numbers of cases,
and that's probably a minimal estimate."
https://medicalxpress.com/news/2020-07-mayo-clinic-covid-expert-virus.html
6 types of COVID-19, sorted by symptoms;
3 types are tied with the most severe disease.
Using a mix of symptoms, body weight and other factors,
researchers developed a model that predicts
which patients will need to be hospitalized and need breathing support.
https://medicalxpress.com/news/2020-07-covid--1.html
Using the Oak Ridge National Laboratory Summit supercomputer to analyze genes
from cells in the lung fluid of nine COVID-19 patients compared with 40 control patients
suggests that genes related to one of the body's systems responsible for lowering blood pressure
- the bradykinin system - appear to be excessively "turned on"
in lung fluid cells of those with the virus, allowing fluid build up in their soft tissues.
If this disease mechanism model is accurate and substantiated by experimental analysis,
existing medicines could perhaps be repurposed to slow the pathogenesis of COVID-19.
"When the lungs end up with an excess of hyaluronic acid in them,
it's like trying to breathe through Jell-O"
https://elifesciences.org/articles/59177
Tasso has received $17 million in new funding to scale up production
of its
self-administered blood collection devices,
designed to help enable telemedicine and home diagnostic testing.
FDA authorizes LabCorp's as first symptomless COVID-19 screening test
Previous FDA testing EUAs were reserved for people showing early signs of an infection,
such as a fever, as well as high-risk individuals and front-line healthcare workers
- both to conserve testing resources and because most tests had not been proven accurate
enough to screen large numbers of people without unacceptable false positive or negative results.
On top of an earlier $483 million,
Moderna receive another $472M from
U.S. government-funded Biomedical Advanced Research and Development Authority (BARDA)
for its Phase 3 COVID-19 vaccine trial, the world's largest to date. "We thank BARDA
for this continued commitment to mRNA-1273, our vaccine candidate against COVID-19."
Computational molecular modeling of key interactions
between SARS-CoV-2 main protease and inhibitor drug candidates.
Pharmacophore modeling is one ligand-based drug discovery technique
to identify common features of ligands to bind to the target protein.
https://www.nature.com/articles/s41598-020-69337-9
Certain common infections coming together with a less hygienic lifestyle
may trigger the human immune system and thus facilitate some protection against CoVID-19,
an argument similar to the so-called 'hygiene hypothesis'.
In this study, toxoplasmosis is a proxy for hygiene.
https://www.nature.com/articles/s41598-020-69351-x
At least 80,856 people have tested positive for the coronavirus in South Carolina,
with 1,170 cases reported Sunday, down from 1,368 Saturday and the fewest since July 7.
SC DHEC did not announce hospitalization information Sunday,
saying hospitals are transitioning to a new federal [non]reporting 'system'.
A federal judge turned down a request from a New Jersey inmate
for compassionate release to his Colleton County home.
"Three months ago, the notion that a person would be at greater risk
for exposure to COVID-19 in South Carolina
than in a prison in New Jersey was preposterous,"
"Yet, here we are."
The 12-bed intensive care unit at Beaufort Memorial Hospital hit its capacity Friday morning.
https://www.thestate.com/news/coronavirus/article244501937.html
A patent court has sided with Arbutus Biopharma, in that Moderna
failed to show claims made in its patent "would have been anticipated or obvious."
Moderna licensed lipid nanoparticle (LNP) technology from Acuitas to enable mRNA delivery.
This intellectual property dispute could stymie COVID-19 vaccine development. pandemic engineering (slow Sunday)
Pandemic spread is driven by diffusion:
An essential bit about diffusion is that flux (AKA magnitude and direction of flow )
is linearly proportional to density gradient of diffusing material concentration.
Diffusion gets complicated by geometries and nonuniformities,
so let's back off and use engineering approximations e.g. from electronics,
with electrons analogous to viral particles and electrical potential analogous to particle density.
One electrical property, capacitance C, is defined as the ratio of electron charge to potential: C = Q / V or V = Q / C.
In this analogy, a specific human's breathing system has relatively constant capacity,
and potential to diffuse viral particles is proportional to instantaneous particle concentration.
Another well-known electrical law was named after Georg Ohm: V = I * R, where I is time rate of change in charge: I = Q / T
.. and R is resistance to that change.
Applied to our specific human, exhaling into a vacuum,
which represents practically no resistance,
initial flux would be very large while particle density
(along with survival odds) would quickly approach zero.
Alternatively, attempting to exhale into high water pressure encounters higher resistance,
although viral particles would readily diffuse into that water,
provided that water initially has relatively low viral particle concentration.
Electrical power (AKA energy flow) P = I*V = I*I*R = V*V/R
Perhaps unintuitively, no power is consumed even for large current flows
where there is no resistance. On the other hand,
even a small potential into a smaller resistance consumes substantial power.
Much of electrical engineering involves one dimensional flows,
with electron flows into near ends of conductors equal those at far ends.
However, antenna radiation involves 3-dimensional geometry
and inverse square law
with an implicit assumption of free space,
which is emphatically NOT applicable for viral transmission indoors.
An inverse-square relationship arises from consideration that
flow thru one surface is spread over 4 times the area of another surface with twice the diameter,
with another implicit assumption that flow continues onword, uninterrupted.
This distancing effect is essentially nullified in effectively closed indoor spaces,
where transmission is mostly determined by duration of exposure and source flow rate.
Back to antennas: given directionality, radio engineers think in terms of ERP
.. 3 feet behind a COVID-19 carrier may be safer than 6 feet in front.
Back to the capacitor analogy: COVID-19 patients have relatively fixed capacities
but are also relatively constant viral generators. Consequently,
larger, quiet, and inactive nose breathers may accumulate higher concentrations
than smaller, noisy, active mouth breathers (AKA children). Higher concentrations presumably
promote more reinfection as well as contagion when they do speak, sneeze or sing.
I speculate that one is unlikely to become sick by inhaling a single SARS-CoV-2 virus.
I'll even speculate that very small doses may help develop immunity with minimal symptoms.
Conversely, there may be an optimal spacing and duration
for a single COVID-19 patient to most efficiently infect others,
which is analogous to matching electrical impedances for maximum power flow.
Motivation for writing this includes an insight that
SARS-CoV-2 transmission power is probably related to the square of viral concentration,
just as electrical power is proportional to the square of potential
(for a constant system impedance).
That nonlinear effect would help explain super-spreaders..
35% of people who had COVID-19 and were able to self-treat
were still not at their usual level of health two to three weeks after testing.
For people ages 18 to 34 with no underlying health issues,
1 in 5 were still feeling ill weeks later.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm
Altered olfactory function is a common symptom of COVID-19.
Single cell sequencing revealed that ACE2 is expressed in support cells,
stem cells, and perivascular cells, rather than in neurons.
Bulk sequencing demonstrated that CoV-2 infection of non-neuronal cell types
leads to anosmia and related disturbances in odor perception in COVID-19 patients.
Recovery from COVID-related anosmia often occurs over weeks,
while recovery from typical post-viral anosmia
- which is often caused by direct damage to olfactory sensory neurons - frequently takes months.
https://advances.sciencemag.org/content/early/2020/07/24/sciadv.abc5801.1
Biologically, a COVID-19 vaccine is unlikely to offer complete protection.
Logistically, manufacturers must make hundreds of millions of doses while relying, perhaps,
on technology never before used in vaccines and competing for supplies such as glass vials.
Then the federal government will have to allocate doses, perhaps through a patchwork of
state and local health departments with no existing infrastructure for vaccinating adults at scale.
https://www.theatlantic.com/health/archive/2020/07/covid-19-vaccine-reality-check/614566/
Rheumatoid arthritis drug anakinra, in a study involving 22 very ill patients,
"all of the patients treated with anakinra improved clinically with no deaths,
significant decreases in oxygen requirements,
and more days without invasive mechanical ventilation."
https://www.pnas.org/content/early/2020/07/21/2009017117
ARCoV is a messenger RNA vaccine, using technology similar to Moderna's candidate.
It is the second potential COVID-19 vaccine
that China's military-backed research unit has moved into clinical trials.
Results of trials of ARCoV in mice and monkeys,
published in the peer-reviewed medical journal Cell on Thursday,
show both single and two-dose inoculations induced strong antibody and T-cell responses
against several COVID-19-causing virus strains.
https://reader.elsevier.com/reader/sd/pii/S0092867420309326
SARS-CoV-2 produces an enzyme called nsp16 that modifies its messenger RNA cap.
"Because of the modifications, which fool the cell,
the resulting viral messenger RNA is now considered as part of the cell's own code
and not foreign."
https://www.nature.com/articles/s41467-020-17496-8
A simple and rapid SARS-CoV-2 surrogate virus neutralization test (sVNT)
has been developed that detects neutralizing antibodies for determining
not only infection rate, herd immunity and predicted humoral protection,
but also vaccine efficacy during clinical trials and after large-scale vaccination.
https://www.nature.com/articles/s41587-020-0631-z
Another 21 existing drugs have been identified to stop SARS-CoV-2 replication.
4 of these were found to work synergistically with remdesivir,
a current standard-of-care treatment for COVID-19, including
the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug
that has reached Phase 3 clinical trials.
"Based on our current analysis, clofazimine, hanfangchin A, apilimod and ONO 5334
represent the best near-term options for an effective COVID-19 treatment"
https://www.sbpdiscovery.org/news/nature-study-identifies-21-existing-drugs-could-treat-covid-19
Despite Roche's first overall quarterly sales decline in nearly a decade,
the demand for coronavirus testing drove a 61% increase in molecular diagnostic sales
over the first half of this year, with new products aimed at COVID-19
potentially offsetting the negative impacts from people postponing routine medical testing.
Overall, Roche's diagnostic sales rose 3% to 6.1 billion Swiss francs, or about $6.6 billion U.S.
https://www.roche.com/investors/updates/inv-update-2020-07-23.htm
The current state of antibody testing for COVID-19 is "a disaster,"
said Roche CEO Severin Schwan.
"These tests are not worth anything, or have very little use"
Mathematical models to guide pandemic response
As theoretical biologist Robert May wrote: "the virtue of a mathematical model
...is that it forces clarity and precision upon conjecture, thus enabling
meaningful comparison between the consequences of basic assumptions and the empirical facts"
Most antibodies bind to the spike protein on the surface of SARS-CoV-2.
Columbia researchers showed that their cocktail of antibodies
target one of two locations on the S protein: either the receptor binding domain (RBD),
which helps the virus latch onto and infect human cells, or the N-terminal domain (NTD).
https://www.nature.com/articles/s41586-020-2571-7
As long waits for results render COVID-19 tests 'useless,' states seek workarounds.
"It's rather preposterous that you get a test and 13, 14 days later you get the results"
Secaucus, New Jersey-based Quest Diagnostics, one of the nation's largest diagnostic testing companies,
told state officials last week that it was at capacity
and would be unable to accommodate more tests for two or three weeks.
Quest handles about 130,000 tests daily in 20 laboratories,
and its ability to expand has been limited by a global shortage
of machines and chemical reagents needed to perform COVID-19 testing.
Return times vary widely by company. LabCorp said turnaround time
for outpatient test results improved to three to five days this week from four to six last week.
BioReference Laboratories, another big lab chain, said it has improved turnaround time
from about six days in June to three or fewer this month. Walmart,
which has used Quest and eTrueNorth for more than 150,000 COVID-19 tests,
said on its website that Quest results take a week, compared with three to five days with eTrueNorth.
https://khn.org/news/states-search-for-ways-to-deal-with-covid-19-testing-backlogs/
CU Boulder researchers have developed a rapid, portable, saliva-based
RT-LAMP COVID-19 test able to return results in 45 minutes.
"The test predicted with 100% accuracy all of the negative samples,
and 29 of 30 positive samples were predicted accurately"
Quick turnaround for testing is more critical to curbing the pandemic than test sensitivity.
https://www.medrxiv.org/content/10.1101/2020.07.16.20150250v1
Well-known anticoagulant heparin was recently shown to have
exceptional binding affinity to the spike protein (S-protein) of SARS-CoV-2.
A follow-on study revealed specific closely related sulfated polysaccharides
bind tightly to the S-protein of SARS-CoV-2 in vitro, which suggests that
they can act as decoys to interfere with S-protein binding to the heparan sulfate co-receptor in host tissues.
Treatment using fucoidans, nebulized heparin, or possibly TriS-heparin in combination
with or without current antiviral therapies, should be assessed first in human primary epithelial cells
and then in human patients suffering from COVID-19.
https://www.nature.com/articles/s41421-020-00192-8
Wrong but Useful - What COVID-19 Epidemiologic Models Can and Cannot Tell Us
COVID-19 modeling studies generally follow one of two general approaches
that we will refer to here as forecasting models and mechanistic models.
Although there are hybrid approaches, these two model types tend to address
different questions on different time scales, and they deal differently with uncertainty.
Forecasting models are often statistical in nature,
fitting a line or curve to data and extrapolating from there
The original versions of the controversial model
from the Institute for Health Metrics and Evaluation (IHME) fell into this category
Mechanistic models, like the Susceptible-Exposed-Infectious-Recovered frameworks,
mimic the way SARS-CoV-2 spreads and can be used to forecast or simulate future transmission scenarios
under various assumptions about parameters governing transmission, disease, and immunity.
Unlike purely statistical models, mechanistic approaches include important feedback
- the more people become infected, the faster disease spreads.
In fact, many parameters associated with COVID-19 transmission are poorly understood.
The resulting model uncertainty is not always calculated or reported in a standardized way.
https://www.nejm.org/doi/full/10.1056/NEJMp2016822
Shut down the country and start over to contain COVID-19
- open letter from U.S. medical experts urging political leaders
"Right now, we are on a path to lose more than 200,000 American lives by November 1st."
We need enough daily testing capacity to test everyone with flu-like symptoms
plus anyone they have been in close contact with over the last 2 weeks
(at least 10 additional tests per symptomatic person).
We currently have only 35% of that testing capacity.
https://uspirg.org/sites/pirg/files/USP_Public-health_final-letter-shutdowns.pdf
Pandemic has half of U.S. hospitals operating at a loss
"this pandemic is the greatest financial threat in history for hospitals and health systems,
and is a serious obstacle to keeping the doors open for many"
https://medicalxpress.com/news/2020-07-pandemic-hospitals-loss.html
Arrayed imaging reflectometry starts with a strong anti-reflective coating
spread across the surface of a standard-shaped well plate
that captures and deflects as much light as possible.
Capture probes are arrayed on top to bind with a range of different target molecules.
After adding a sample, a laser is used to scan each well.
As more target molecules bind to the surface, more light is reflected and captured,
delivering a clear signal of whatever is present in one step
- such as antibodies for the novel coronavirus or other diseases,
or the cytokine regulators of the body's immune system.
Planned for August release, Adarza Biosystems is in the midst of beta testing
the first release of its acute respiratory panel with multiple targets for SARS-CoV-2,
including antigens aimed at its spike protein and variants of its binding domains.
https://www.bioworld.com/articles/436012-adarzas-ziva-provides-window-into-immune-response-to-covid-19-and-other-pathogens
Host-directed therapy uses the body's own immune system to deal with the infection.
A Trinity College Dublin research team repurposed SAHA,
an epigenetic inhibitor approved for cancer treatment,
to stop production of an anti-inflammatory signal
while at the same time promoting more appropriate pro-inflammatory signals
that may help the patient to clear the infection.
Importantly, this fine-tuning of the immune response
early in the reaction to infection also benefits later immune responses,
which may also aid in the design of future vaccine strategies.
https://www.tcd.ie/news_events/articles/driving-immunometabolism-to-control-lung-infection/
About 30% (190) of long-term care homes in Ontario, Canada experienced outbreaks
from March 29 to May 20, 2020, with 110 (30.6%) occurring in for-profit homes,
55 (34%) in nonprofit homes and 25 (24.8%) in municipal homes.
For-profit status was associated with about a two-fold increase
in the extent of a COVID-19 outbreak (number of resident cases)
and a 178% increase in the number of resident deaths compared with homes with non-profit status.
https://www.cmaj.ca/content/cmaj/early/2020/07/22/cmaj.201714.full.pdf
America now stands almost alone among wealthy nations for its failure to contain the disease.
Average death rates hit new highs in Alabama, Arizona, Florida, South Carolina and Texas over the weekend,
and at least 18 states set records for average weekly infections.
"If there was a mistake to be made in this pandemic, America has made it."
CDC reports from this Spring:
just 1% of people in the San Francisco Bay area had antibodies;
on the other end of the spectrum, New York's antibody rate was 6.9%.
U.S. COVID-19 case count 6 to 24 times higher than reported.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768834
Since immunity may be short-lived, perhaps grey bar counts should be time-limited..
Blood samples analyzed by enzyme-linked immunosorbent assay (ELISA)
to detect anti-SARS-CoV-2 spike receptor-binding domain IgG in 34 COVID-19 patients
indicated a half-life of approximately 73 days:
https://www.nejm.org/doi/full/10.1056/NEJMc2025179
Virus antibodies fade fast but not necessarily protection
[ no actual data here ] Besides churning out antibodies,
B cells develop a memory so they know how to do that again if needed.
"They would get called into action very quickly when there's a new exposure to the virus.
It's as if they lie dormant, just waiting,"
https://medicalxpress.com/news/2020-07-virus-antibodies-fast-necessarily.html
Why America's public health system can't withstand Trump
The federal government must play a critical role in providing resources and coordinating amongst states
during a public health crisis. The CDC collects and publishes data on outbreaks,
the FDA approves vaccines and treatments, the NIH directs and funds scientific research.
The feds can allocate supplies, issue guidance for states and cities to follow,
and provide money for state and local health departments to perform their vital duties.
https://www.vox.com/2020/7/20/21331702/trump-coronavirus-health-care-america
Dr. Peter Hotez of the Baylor College of Medicine said Southern states like Texas and Florida are seeing increased deaths
because "the hospitals are overwhelmed." The situation has grown so dire that Hidalgo County officials
threatened this week to criminally prosecute people who don't quarantine after testing positive for COVID-19.
Hidalgo County Judge Richard Cortez issued a shelter-at-home order for all residents starting Wednesday.
https://www.cnn.com/2020/07/22/us/hidalgo-county-south-texas-covid-19/index.html
SC tourist destinations Myrtle Beach and Hilton Head Island have
ramped up their marketing efforts with state and local leaders encouraging tourism
while failing to make any substantial decisions that could significantly limit
the spread of coronavirus as cases continue to boom.
https://www.thestate.com/news/state/south-carolina/article244214697.html
Review of British NHS RECOVERY trial of 6425 patients
who were assigned to receive dexamethasone or usual care:
dexamethasone showed promise for reducing short-term mortality relative to usual care,
but benefits of dexamethasone may be restricted to the sickest of COVID-19 patients,
those who had been placed on mechanical ventilation at the time of randomization.
https://www.nejm.org/doi/full/10.1056/NEJMe2025674
A series of autopsies conducted by LSU Health New Orleans pathologists
led by Dr. Vander Heide, an experienced cardiovascular pathologist, found that
unlike the first SARS coronavirus, SARS-CoV-2 was not present in heart muscle cells.
Nor were there occluding blood clots in the coronary arteries.
https://medicalxpress.com/news/2020-07-autopsies-reveal-cardiac-covid-patients.html
An Ad5 vectored COVID-19 vaccine candidate phase 2 trial conducted in China found
it safely inducing an immune response, according to new research published in The Lancet.
Pfizer and BioNTech phase 1/2 data suggests their COVID-19 vaccine
triggers stronger CD8 T-cell responses than Moderna's rival candidate.
Four-fifths of subjects who received BNT162b1 had vaccine-induced CD8 T-cell responses,
and researchers classed most of the responses as strong.
Pfizer and BioNTech plan to assess the efficacy of their vaccine
in a 30,000-subject phase 2b/3 trial that is due to start this month.
https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1.full.pdf
SARS-CoV-2 binds tightly to heparin, widely used to treat and prevent blood clots,
making the drug a potential "decoy" that could serve as a way
to neutralize the virus before it can infect healthy cells.
https://reader.elsevier.com/reader/sd/pii/S0166354220302874
In a double-blind placebo-controlled trial of Synairgen's aerosol-based SNG001on 101 COVID-19 patients,
79% had lower risk of developing severe disease, compared to placebo and were more than twice as likely to recover.
Antibody responses to SARS-CoV-2 short-lived
This preprint describes a longitudinal analysis of antibody responses in 65 SARS-CoV-2-infected individuals.
Magnitude of neutralizing antibody (nAb) responses correlated with disease severity,
but nAb titres declined rapidly in most patients within 3 months of symptoms onset.
https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1
SARS-CoV-2 dissociated from fatal inflammations.
Post-mortem tissues from 11 patients showed severe inflammation limited to the lung
and reticuloendothelial system and was not consistently associated with presence of virus,
despite wide distribution of viral products in pulmonary and extra-pulmonary tissues.
https://www.medrxiv.org/content/10.1101/2020.07.02.20145003v1
Australian Researchers Develop 20-Minute COVID-19 Blood Test
The test requires 25 microliters of plasma from blood samples,
and positive COVID-19 cases will cause agglutination or clustering of the red blood cells,
which is easily identifiable to the naked eye.
Inventors claim medical practitioners could test up to 200 blood samples an hour in a simple lab setup,
and hospitals with high-grade diagnostic machines could test about 16,800 blood samples each day.
https://pubs.acs.org/doi/10.1021/acssensors.0c01050
In other clown news:
* FL teachers union files lawsuit to stop governor from reopening schools
The suit alleges that the July 6 emergency order requiring all public K-12 schools
in the state to allow on-site classes is a violation of the Florida Constitution.
"Florida's Constitution demands that public schools be safe.
Teachers and parents want our schools to meet that basic standard."
https://www.washingtonexaminer.com/news/largest-florida-teachers-union-sues-desantis-administration-over-school-reopening-plans
test results within one day and tracing 80% of contacts could reduce transmission 80%
For the most optimistic scenario (testing and tracing delays of 0 days and 100% tracing coverage),
and assuming that around 40% of transmissions occur before symptom onset,
the model predicts that the estimated effective reproduction number of 1.2
(with physical distancing only) will be reduced to 0.8 (95% CI 0.7-0.9) by adding contact tracing.
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(20)30157-2/fulltext
Texas Gov. Abbott said the U.S. Department of Defense has sent five U.S. Navy teams,
consisting of medical and support professionals, to support hospitals in Harlingen, Del Rio,
Eagle Pass and Rio Grande City,
after more than 10,000 cases reported for 5 consecutive days.
Up to 165 countries, more than 60% of the world's population, joining COVAX Facility
The COVAX Facility forms a key part of the COVAX pillar (COVAX) of the Access to COVID-19 Tools (ACT) Accelerator,
sharing the risks associated with vaccine development, investing in manufacturing upfront
so vaccines can be deployed at scale as soon as they are proven successful,
and pooling procurement and purchasing power for 2 billion doses to end the acute phase of the pandemic by 2021.
https://www.who.int/news-room/detail/15-07-2020-more-than-150-countries-engaged-in-covid-19-vaccine-global-access-facility
Trump administration seeks to block money for testing, tracing, CDC in upcoming virus relief bill.
The administration is also trying to block billions of dollars that GOP senators want to allocate
for the Centers for Disease Control and Prevention, and billions more for the Pentagon and State Department
to address the pandemic at home and abroad.
FDA finally authorizes first pool testing
Quest SARS-CoV-2 rRT-PCR test received EUA for up to four pooled COVID-19 samples.
Data demonstrates that its test correctly identified all pooled samples with a positive sample.
Inside the Failure: 5 Takeaways on Trump's Effort to Shift Pandemic Responsibility
Critical decisions were made mid-April not by the better known coronavirus task force,
but instead by a small group of White House aides who convened each morning
in the office of the president's chief of staff, misinformed by Dr. Deborah L. Birx,
who evangelized that infections had peaked and the virus was fading quickly,
based on a model that failed to account for how reopening would disrupt mitigations.
https://www.nytimes.com/2020/07/18/us/politics/trump-coronavirus-failure-takeaways.html
"Don't come and say you want something from the state when you haven't followed the rules.
There are consequences. These are the consequences."
Pennsylvania reported 1,031 new known coronavirus cases on Friday,
the second time in the last week that the daily total exceeded 1,000.
The state is now averaging 800 new cases a day over the last seven days.
More than 70,000 new COVID-19 infections and more than 900 deaths were reported Thursday.
"In California, doctors are shipping patients as many as 600 miles away
because they can't be cared for locally. In Florida, nurses are pouring in from out of state
to reinforce exhausted medical workers. And in Texas,
mayors are demanding the right to shut down their cities to avoid overwhelming hospitals."
A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1)
which suppresses host gene expression by ribosome association.
Structural analysis by cryo-electron microscopy
revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel.
Thereby, Nsp1 effectively blocks RIG-I-dependent innate immune responses
that would otherwise facilitate clearance of the infection.
https://science.sciencemag.org/content/early/2020/07/16/science.abc8665
We find that a resurgent continental epidemic could occur
as many as 5 weeks earlier when well-connected countries
with stringent existing interventions end their interventions prematurely. Further,
we found that appropriate coordination can greatly improve the likelihood of eliminating community transmission throughout Europe.
In particular, synchronizing intermittent lockdowns across Europe meant half as many lockdown periods were required
to end community transmission continent-wide.
https://science.sciencemag.org/content/early/2020/07/16/science.abc5096
Full results from a UK trial of the steroid dexamethasone were published Friday,
confirming its life-saving benefits for COVID-19 patients on ventilators
but suggesting it may cause harm if given too early.
https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
Recurrence of positive SARS-CoV-2 viral RNA in 10 of 182 recovered COVID-19 patients
during medical isolation observation; none showed any clinical symptomatic recurrence.
https://www.nature.com/articles/s41598-020-68782-w
China's Sinopharm begins Phase 3 inactivated COVID-19 vaccine trials, expected to last for three to six months,
in United Arab Emirates, evaluating two formulations of the vaccine,
which demonstrated a 100% immune response in phase 1 and 2 clinical trials, in 15,000 volunteers ages 18-60.
https://www.reuters.com/article/us-health-coronavirus-emirates-vaccine-idUSKCN24H14T
A modeling study showed that even if all contacts are successfully traced,
a delay of three days or more between the start of symptoms and testing
will not reduce transmission of the virus sufficiently to control further spread.
https://medicalxpress.com/news/2020-07-contact-useless-speedy.html
"Absent a few positive tests among protesters announced here and there,
the only major outbreak tied to protests happened in South Carolina,
where organizers postponed demonstrations or moved them online
after at least 13 people who took part in previous protests tested positive."
three distinct immune responses for COVID-19 patients
The first immunotype had robust CD4+ T cell activity,
with modest activation of CD8+ T cells and peripheral blood lymphocytes.
CD4+ and CD8+ act as the main inflammatory immune cells that work to clear viruses.
The second immunotype was characterized mainly by
a subset of CD8+ T cells known as EM and EMRA
and a modest activation of CD8+ T cells, memory B cells, and peripheral blood lymphocytes.
The third immunotype showed little to no evidence of an immune response to the infection.
The first immunotype was tied to more severe disease
that included inflammation, organ failure, and acute kidney disease.
The second correlated not with disease severity
but instead pre-existing immunosuppression and mortality.
The third type was not associated with specific symptoms or clinical features,
though they varied.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263500/
Coronavirus data has already disappeared after Trump administration shifted control from CDC
"HHS has directed CDC to re-establish the coronavirus dashboards
it withdrew from the public on Wednesday.
A total of 24 observational studies including 10,150 patients were identified from centres across Asia, Europe and North America.
In patients with completed ICU admissions with COVID-19 infection,
combined ICU mortality across all the studies up to the end of May was 41.6%.
This represents a fall of around a third from the 59.5% ICU mortality seen in the studies
up to the end of March. "The in-ICU mortality from COVID-19, at around 40%,
remains almost twice that seen in ICU admissions with other viral pneumonias, at 22%."
https://anaesthetists.org/Home/News-opinion/News/COVID-19-intensive-care-mortality-falls-by-a-third
Preventing COVID-19 'price gouging'
Dr Giosa argues that, rather than imposing fines on companies that overcharge,
it would be more effective for NCAs and the European Commission to seek commitment from companies guilty of price-hiking,
to discontinue their anti-competitive conduct and agree to set lower prices in future.
The article also makes a case for the application of price controls.
https://academic.oup.com/jeclap/article/doi/10.1093/jeclap/lpaa029/5871453
JPMorgan Chase, Citigroup and Wells Fargo set aside billions in capital
as they prepare for customers to default on loans.
"Our view of the length and severity of the economic downturn has deteriorated considerably"
Data is for sissies
As part of a new data reporting protocol for hospitals
that eliminates the CDC as a recipient of pandemic information,
the Trump administration is asking governors to
consider sending the National Guard to hospitals
to help improve data collection about novel coronavirus patients, supplies and capacity,
according to a letter, internal emails and officials familiar with the plans.
good news
1) Additional therapeutic treatments will arrive before vaccines.
... but
demand could outstrip supply
2) Rapid, low-cost saliva tests are also coming
3) Even some red state leaders now urge mask wearing
4) Consensus on airborne spread
5) common-cold coronaviruses immune cells may help against COVID-19
6) Vaccine trials seem to be working
Moderna "positive" early data published for mRNA-1273. Despite the "robust" responses,
"correlates of protection from SARS-CoV-2 infection have not been determined."
https://www.nejm.org/doi/full/10.1056/NEJMoa2022483
Hebrew University of Jerusalem (HU)'s Professor Yaakov Nahmias and Dr. Benjamin tenOever
at New York's Icahn School of Medicine at Mount Sinai
observed that SARS-CoV-2 prevents routine burning of carbohydrates,
with fat accumulating inside lung cells, which may help
explain why patients with high blood sugar and cholesterol levels are often at a particularly
high risk to develop COVID-19. "By understanding how the SARS-CoV-2 controls our
metabolism, we can wrestle back control from the virus
and deprive it from the very resources it needs to survive."
In lab studies, cholesterol-lowering drug Fenofibrate (Tricor) showed promising results.
By allowing lung cells to burn more fat, fenofibrate prevents SARS CoV-2's reproduction.
Within only five days of treatment, the virus almost completely disappeared.
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3650499
Canyon Creek Memory Care, in Billings, Montana, refused free tests.
Now, nearly everyone has virus, killing 8 since July 6,
accounting for almost a quarter of Montana's 34 confirmed deaths.
Thirty-six employees also have tested positive.
https://medicalxpress.com/news/2020-07-home-free-virus.html
Travelers from 22 states will be required to quarantine for 14 days upon entering New York.
The percentage of people testing positive for the coronavirus ticked up to 1.5%
from a level of about 1% where it had been since mid-June.
"It's also clear based on contact tracing that
many of the new cases in New York are a result of a lack of compliance
during the July 4 weekend and illustrate how quickly the virus spreads,
with one party, for example, infecting more than a third of attendees."
https://medicalxpress.com/news/2020-07-states-added-ny-coronavirus-quarantine.html
Computational immunology and COVID-19 vaccine development
"If we know what's conserved in all of these different influenza viruses,
we can combine that with what's conserved in the human body response"
"Mathematical models, statistical approaches, and machine learning
are the only way you can make meaning out of so much data"
"There's no shortcut to actually doing the experiment"
https://www.nature.com/articles/d41591-020-00027-9
New Jersey is requiring residents wear masks outdoors when social distancing is difficult.
Face masks are mandatory in public spaces in Pennsylvania and Delaware.
The U.S. COVID-19 testing system is still hobbled by supply-chain failures.
"It's not shortages of any one thing. It's now spot shortages of all of them,"
said Scott Becker, chief executive of the Association of Public Health Laboratories.
"Clinical labs need more swabs, chemical reagents, viral transport media, test kits,
machines to process the tests, staffing to run the machines." As a result,
many of the millions of tests conducted in recent weeks took so long to complete
that the results were basically useless for tracing and isolating outbreaks.
Friday to Sunday coronavirus deaths up 70% over a week ago in the U.S.
Despite Florida recording its highest one-day total to date over the weekend,
thousands turned out for Walt Disney World's reopening. U.S. hot spots:
https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.htm
In an integrated immune analysis on 50 COVID-19 patients with various disease severity,
a unique phenotype was observed in severe and critical patients,
consisting of a highly impaired interferon (IFN) type I response
(characterized by no IFN-B and low IFN-a production and activity),
associated with a persistent blood viral load and an exacerbated inflammatory response.
https://science.sciencemag.org/content/early/2020/07/10/science.abc6027
While hospital patients can get COVID-19 findings back within a day,
people tested at urgent care centers, community health centers, pharmacies
and government-run drive-thru or walk-up sites
are often waiting a week or more.
Atlanta Mayor Keisha Lance Bottoms, who announced Monday that she had tested
positive for the virus, waited eight days for her results
As Moderna has been apparently squabbling with the government
and making last-minute protocol changes to its late-stage effort,
Pfizer and BioNTech have been granted FDA fast track designation
as they, like Moderna, now plan a phase 2b/3 trial start
"as soon as later this month," the partners said in a statement this morning,
and they are "anticipating enrolling up to 30,000 subjects."
While ordering travelers from more than a dozen states to quarantine for 14 day,
NY has offered advice, ventilators, masks, gowns and medicine
to states dealing with spikes in cases and hospitalizations and, in some places, rising deaths.
Some health care workers are heading to other states to help fight the virus,
reciprocating the influx that gave New York hospitals some much-needed relief just months ago.
https://medicalxpress.com/news/2020-07-virus-rages-york.html
Based on data from tests for common respiratory viruses and SARS-CoV-2,
symptom-based screening may not be an effective strategy
to identify individuals who should be tested for SARS-CoV-2 infection
or to obtain a leading indicator of new COVID-19 cases.
https://www.nature.com/articles/s41746-020-0300-0
Barefaced Floridians embrace inalienable right to kill their neighbors
"If their collective intransigence results in a brutal surge of coronavirus infections
and hospitalizations, so what? If the nation suffers another hundred thousand COVID-19 fatalities,
that's a cheap price to pay for the freedom to bar hop without a face covering."
SARS-CoV2 vaccines: Slow is fast
Phase 3 trials are necessarily time consuming and require that
infection among the control group is sufficiently high to draw a conclusion.
In 1966, a large trial of a vaccine for respiratory syncytial virus (RSV) found that
the immunized cohort actually faired significantly worse upon infection.
There is some reason to worry that the same may occur with some SARS-CoV2 vaccines.
Any immune response is of two types, adaptive or innate.
Adaptive immunity is elicited by most vaccines and is mediated by lymphocytes.
With the failed RSV vaccine, a lack of antibody affinity maturation caused the negative effect.
There are potential reasons why an immune response to a vaccine can predispose an individual
to a worse outcome upon infection. One is the phenomenon of antibody-dependent enhancement (ADE).
Troublingly, ADE has also been seen with vaccines for a feline coronavirus (6, 7).
There is also evidence for ADE in SARS-CoV.
https://advances.sciencemag.org/content/6/28/eabc7428
Governors across the country are facing growing pressure from public health experts
and local leaders to reimpose stay-at-home orders as the only way to regain control of
coronavirus outbreaks that threaten to overwhelm hospitals and send the death count rocketing.
"Stay-at-home is a blunt instrument," said Farshad Fani Marvasti,
director of public health at the University of Arizona College of Medicine Phoenix.
"But when you're leading the world in new cases and things don't seem to be getting better,
you may have to use that blunt instrument."
Comprehensive review of COVID-19's effects outside lungs
* Blood Clots, Inflammation, and an Immune System in Overdrive
* Heart, Kidney and Neurological effects
https://www.nature.com/articles/s41591-020-0968-3
A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate
Of 8 vaccine candidates, researchers at Belgium's Rega Institute found one,
based on the existing vaccine against yellow fever, highly effective in hamsters.
Hamsters receiving the vaccine had few to no traces of coronavirus in their lungs after exposure.
Clinical trials are aimed to start next winter.
https://www.biorxiv.org/content/10.1101/2020.07.08.193045v1
Novavax was recently awarded over $1.6 billion by the U.S. misgovernment
to support commercial-scale manufacturing of their potential coronavirus vaccine
Johnson & Johnson, Moderna and AstraZeneca also received Operation Warp Speed funding.
Novavax's candidate is based on adjuvanted recombinant nanoparticle vaccine technology,
which is more proven than Moderna's mRNA or Inovio's DNA candidate.
Although manufacturing should be quicker and easier than making traditional vaccines,
no human vaccine approved so far uses either the mRNA or DNA approach.
Massive Korean contact-tracing effort found hundreds of cases linked to nightclubs.
The team found that testing 5000 students every 2 days with a rapid and relatively cheap test
would keep infections to around 135 over the semester, and cost $470 per student per term.
However, testing only weekly would result in an explosive growth in infections.
https://www.nature.com/articles/d41586-020-00502-w
Rapid isolation and profiling of a diverse panel of human monoclonal antibodies
targeting the SARS-CoV-2 spike protein
Using Zika virus as a simulated pandemic pathogen and leveraging recent technological advances
in synthetic genomics and single-cell sequencing, researchers recently isolated hundreds of human mAbs
from a single-B-cell suspension and tested them in vitro for neutralization
and for protection in small animals and non-human primates, all within 78 days.
Using similar methodologies and further efficiency improvements, they obtained
human mAbs for SARS-CoV-2 within weeks after acquiring B cells
from some of the first humans identified with the infection in North America.
Detailed procedural description and graphics:
https://www.nature.com/articles/s41591-020-0998-x
Baylor College of Medicine and 4 other institutions around the U.S.
are recruiting healthcare workers for a
phase 4 clinical trial of BCG tuberculosis vaccine against COVID-19
"Epidemiological studies show that if you're BCG vaccinated,
you have a decreased rate of other infections"
Disease Control, Civil Liberties, and Mass Testing
- Calibrating Restrictions during the COVID-19 Pandemic
The relatively clear criteria for ending conventional quarantine and isolation
don't apply to social restrictions related to COVID-19.
Transmission dynamics of SARS-CoV-2 make it difficult to identify and target risk groups.
More relevant than quarantine-based precedents
are legal challenges to emergency curfews during natural disasters or civil unrest.
https://www.nejm.org/doi/full/10.1056/NEJMp2007637
18% of counties recorded their highest seven-day average Monday,
part of the 38% of counties that recorded highs this month.
The COVID-19 Prevention Trials Network launched with a website for volunteers to be considered when the first trials begin later this month.
At least five such large vaccine trials are planned through the network over the coming months,
along with other preventative treatments like antibody drugs.
https://fortune.com/2020/07/08/coronavirus-vaccine-clinical-trial-volunteers/
Tulsa COVID-19 surge after Trump rally
"The past two days we've had almost 500 cases,
and we know we had several large events a little over two weeks ago, which is about right,"
Tulsa Health Department Executive Director Dr. Bruce Dart told a press conference
before Wednesday's numbers came in. "So I guess we just connect the dots."
Tulsa County has recorded 4,571 confirmed cases,
with a 24.2% increase from last week as of 8 a.m. Thursday, with 72 deaths.
https://www.tulsa-health.org/COVID19
Former Medicare, Medicaid & ACA head Andy Slavitt:
Efforts to invalidate masks are absurd.
Vaccine data from Oxford trial (being run in Brazil) looks strong.
No real safety issues so far. Gives people the antibodies,
but probably more like a flu vaccine (40%?) versus MMR (97%).
Monoclonal antibody therapy confers immunity and may prevent infection advancing.
The time before a vaccine will look crappy. Horrible response in the U.S.
Way too many unnecessary deaths. Fall will be awful.
https://coronavirus.medium.com/there-is-a-light-at-the-end-of-the-tunnel-cbfd5fe4ab72
Jul 9, 2020
Reportedly, none of 2415 medical workers who took daily interferon nose drops got COVID-19
Several interferons were approved decades ago by the FDA,
their immune-boosting powers deployed against diseases including cancer and hepatitis.
https://www.medrxiv.org/content/10.1101/2020.04.11.20061473v2
Stanford trial: Single-Blind Study of a Single Dose of Peginterferon Lambda-1a
Compared With Placebo in Outpatients With Mild COVID-19
https://clinicaltrials.gov/ct2/show/NCT04331899
What do the Covid Consultants do, and why is there a demand for your business?
people think that Covid Consultants are going to come into our place of work
and they're gonna recommend that we get UVC [ultraviolet germicidal irradiation] lighting
and foggers and all these really expensive things,
but that's actually the total opposite of what we do.
You already know those tips. People know them.
But we're human beings, and they don't act on them.
The University of Oxford and its research center in China launch Oxsed Limited,
a new company to develop a rapid COVID-19 test that could cost about $25 U.S.
"Our test is ideal for use in community or field settings by laypersons
and allows immediate decisions to be made"
The single-step test generates a colored result in 30 to 45 minutes from a throat or nasal swab,
and can be read by the naked eye or a digital instrument.
The simplified viral RNA test is based on RT-LAMP technology,
for reverse transcription, loop-mediated isothermal amplification.
The method uses less hardware than the PCR-based coronavirus lab tests in widespread use,
which can require dozens of cycles of heating and cooling to drive the DNA reactions.
"An advantage of using LAMP technology is that
it uses different reagents to most laboratory-based PCR tests"
About half of health care workers positive for COVID-19 by serology have no symptoms
Among 249 front-line health care workers who cared for COVID-19 patients during the first month of the pandemic in Tennessee,
8% tested positive for COVID-19 antibodies by serology testing,
of whom 42% reported no symptoms of a respiratory illness in the prior two months.
https://medicalxpress.com/news/2020-07-health-workers-positive-covid-serology.html
saRNA encapsulated in lipid nanoparticles induce high, Th-1 biased SARS-CoV-2 antibodies
Derived from an alphavirus genome,
self-amplifying RNA (saRNA) encodes the alphaviral replicase and a gene of interest,
enabling RNA replication upon delivery to the cytoplasm.
https://www.nature.com/articles/s41467-020-17409-9
Essential for controlling gene expression within the cell,
microRNAs are also important players in the recognition and destruction of viruses.
One target site on SARS-2 matches an abundant miRNA (miR197) present at very high levels
in patients with cardiovascular complications or with respiratory viral infections.
The miR197 binding site on SARS-2 had been independently mutated
nearly 40 times since March this year and is now present in more than 75% of SARS-2 global isolates.
"Our study suggests that a normal defence pathway in these patients
may have been blocked through this mutation in the virus."
https://medicalxpress.com/news/2020-07-immune-sars-cov-genome.html
French biotech Osivax nabs funding boost for universal flu, coronavirus vaccine work
Osivax, like other universal flu vaccine developers, is striving to equip the immune system to recognize
and target a conserved part of the influenza virus rather than
the rapidly evolving surface antigens at the center of existing prophylactic shots.
Osivax is deploying this same approach toward a universal coronavirus vaccine
to protect against SARS-CoV-2 as well as future coronavirus strains.
https://www.businesswire.com/news/home/20200708005055/en/Osivax-Receives-EUR-30M-Public-Funding-Support
"Controlling the body's inflammatory response is key to the management of COVID-19
and may be as important to managing the pandemic as anti-viral therapies or a vaccine,"
said Dipak Panigrahy, MD, of the Cancer Center at Beth Israel Deaconess Medical Center.
"Our team proposes using molecules made by the body called pro-resolution lipid mediators
- which are currently in clinical trials for other inflammatory diseases -
as a novel approach to turning off the inflammation and preventing the cytokine storm caused by COVID-19."
https://www.bidmc.org/about-bidmc/news/2020/07/approach-to-limit-organ-damage
NIH finally establishes large scale clinical trials
The COVID-19 Prevention Trials Network (COVPN) was established
by merging four existing NIAID-funded clinical trials networks:
the HIV Vaccine Trials Network (HVTN),
based in Seattle; the HIV Prevention Trials Network (HPTN), based in Durham, N.C.;
the Infectious Diseases Clinical Research Consortium (IDCRC) based in Atlanta; and the AIDS Clinical Trials Group based in Los Angeles.
https://www.eurekalert.org/pub_releases/2020-07/nioa-nlc070820.php
Data mining system unearths U.S. counties most at risk for COVID deaths
A new machine learning tool may help gauge areas most at risk for the virus and high death rates.
Analyzing a massive data set from all 3,007 U.S. counties, the software found that combinations of factors such as poverty,
rural settings, low education, low poverty but housing debt, and sleep deprivation are associated with higher county death rates.
https://news.stonybrook.edu/newsroom/data-mining-system-unearths-u-s-counties-most-at-risk-for-covid-deaths/
28 antibodies found to neutralize SARS-CoV-2
After examining more than 4000 SARS-CoV-2-specific B cells on a single cell level,
255 antibodies were reconstructed and test. "Interestingly, many antibodies showed only a small number of mutations.
This means that only minor changes were necessary to effectively recognize and neutralize the virus."
https://www.sciencecodex.com/neutralizing-antibodies-battle-against-covid-19-651405
By brutally exposing the shortcomings of existing diagnostic technologies and clinical testing infrastructure,
COVID-19 is supercharging R&D efforts to establish novel testing approaches that are faster,
simpler, cheaper and more scalable than existing methods, and just as accurate.
https://www.nature.com/articles/s41587-020-0597-x
Traps are boring: building a better mouse
Recently developed models use adenovirus-mediated delivery of human ACE2,
but still express mouse ACE2, which doesn't mediate viral entry, thus limiting their utility.
Inserting cDNAs of human ACE2 into exon 2 of the mouse Ace2 gene,
located on the X chromosome abolished mouse Ace2 expression.
The human ACE2 gene is under control of mouse Ace2 promoter, and
the tissue distribution of ACE2 matches the clinical symptoms of COVID-19 in humans.
https://www.nature.com/articles/s41587-020-0606-0
Lymphocytes display significant reactivity to SARS-CoV-2 antigen peptide pools
was detected in 50% of U.S. donor blood samples collected between 2015 and 2018,
before SARS-CoV-2 appeared in the human population.
https://www.nature.com/articles/s41577-020-0389-z
Last week, the Indian government gave Bharat Biotech and Zydus Cadila permission
to start phase I and II human clinical trials of covaxin and ZyCov-D respectively.
"It is envisaged to launch the vaccine for public health use latest by 15 August 2020 after completion of all clinical trials," wrote ICMR Director-General Balram Bhargava.
"In my knowledge, such an accelerated development pathway has never ever been done
for any kind of vaccine," says Anant Bhan, an independent ethics and policy researcher
and past president of the International Association of Bioethics.
"This seems really, really rushed."
GlaxoSmithKline is continuing its strategy of giving out access to its vaccine platform
as it partners with Canada-based Medicago, to tie its recombinant coronavirus virus-like particles
(CoVLP) with GSK's pandemic adjuvant system, which has been used in previous epidemics.
CoVLPs mimic the structure of SARS-CoV-02, the virus responsible for COVID-19 disease,
allowing them to be recognized by the immune system. A phase 1 is planned within the next week
or so and comes after preclinical testing (and the caveats that brings) showing combining the two
platforms "demonstrated a high level of neutralizing antibodies following a single dose."
https://www.fiercebiotech.com/biotech/glaxosmithkline-pens-covid-19-vaccine-pact-medicago
Large, randomized trials are the gold standard for testing drugs' efficacy,
but they have been scarce so far in the COVID-19 pandemic.
"Everybody has the first part about "randomized," but they omitted the "large" part,
says Ana-Maria Henao Restrepo, a medical officer at WHO Emergencies Programme.
In a sea of small, single institution studies, Recovery, with 12,000 patients
and hundreds of participating hospitals, stands out - and offers lessons for the few other megatrials,
organized by WHO and other bodies, which have been slow off the mark.
Danny Altmann, professor of immunology at Imperial College London, said that
in towns and cities where there had been coronavirus infections,
only 10% to 15% of the population was likely to be immune.
"And immunity to this thing looks rather fragile - it looks like some people might have
antibodies for a few months and then it might wane, so it's not looking like a safe bet"
https://www.cnbc.com/2020/07/06/immunity-to-coronavirus-is-fragile-and-short-lived-expert-warns.html
A month after moving its COVID-19 antibody cocktail into human trials,
NY-based Regeneron is starting a phase 3 trial of REGN-COV2
warding off infection in people exposed to COVID-19 patients.
This study is being conducted at approximately U.S.100 sites
and is expected to enroll 2,000 patients.
Saliva test is less sensitive than swab (more false negatives)
The gold standard for detecting SARS-CoV-2 is a polymerase chain reaction (PCR).
Both saliva and swab tests employ PCR, and saliva has several advantages:
it is easier and less uncomfortable to take
health-care workers may not need to collect
reduced consumption of PPE and swabs, which might be in short supply
However, a recent meta-analysis (not yet peer-reviewed) has shown
detection from saliva is 13% less sensitive than a nasal swab
https://jcm.asm.org/content/jcm/early/2020/04/17/JCM.00776-20.full.pdf
Five pressing questions about COVID-19 being researched
Why do people respond so differently?
What's the nature of immunity and how long does it last?
Has the virus developed any worrying mutations?
How well will a vaccine work?
What is the origin of the virus?
https://www.nature.com/articles/d41586-020-01989-z
What R (reproduction number) can and can't tell us about managing COVID-19
"it's far more important to watch for clusters of cases
and to set up comprehensive systems to test people,
trace their contacts and isolate those infected"
https://www.nature.com/articles/d41586-020-02009-w
U.S. exceptionalism "Men and nations behave wisely once they have exhausted all the other alternatives."
https://eand.co/trump-surrendered-america-to-coronavirus-and-americans-are-paying-the-price-57157b3324df
To propagate, SARS-CoV-2's RNA-dependent polymerase (RdRp) is indispensable
for replicating its genome and generating additional RNAs via transcription.
To treat Ebola, Gilead Sciences developed 'Remdesivir', an adenosine nucleotide analog chain terminator for RdRps,
which incorporated into nascent viral RNA causes premature termination of viral-specific transcription.
In both Gilead's uncontrolled study and NIH's double-blind, placebo-controlled, multicenter trial study,
therapy with Remdesivir reduced recovery time for hospitalized patients with advanced COVID-19.
10-day versus 5-day regimens of Remdesivir demonstrated similar positive outcomes,
suggesting drug efficacy in a shorter time of therapy.
https://advances.sciencemag.org/content/6/27/eabc6891
SARS-CoV-2's entire receptor binding motif
was introduced through recombination with coronaviruses from pangolins,
possibly a critical step in the evolution of SARS-CoV-2's ability to infect humans.
https://advances.sciencemag.org/content/6/27/eabb9153
* Just 2 of 14 coronavirus vaccine candidates in human trials
use old-school approaches, which have some drawbacks.
* Vaccines that preview part of the virus are where most experts are laying their bets.
"It's tried and tested." It's what you get with Hep B, HPV and whooping cough shots,
plus it's worked for coronaviruses in animal models in the past,
but growing virus proteins in a substance like yeast
and then separating it back out again is very difficult and takes months.
* Genetic vaccines inject RNA , a genetic blueprint for the spike protein,
which directs your cells to build it inside of you, which in turn stimulates antibodies.
Of 2,541 patients hospitalized between March 10 and May 2, 2020
across the Henry Ford Health System's 6 hospitals,
13% treated with hydroxychloroquine alone died from COVID-19 disease,
compared to 26.4% not treated with hydroxychloroquine.
The vast majority of these Henry Ford patients received the drug soon after admission,
91% within 48 hours of hospital admission.
The median age was 64 and 56% African American.
No patients had documented serious heart abnormalities.
"We attribute our findings that differ from other studies to early treatment.
Our dosing also differed from other studies not showing a benefit of the drug."
https://www.precisionvaccinations.com/detroit-study-reports-favorable-covid-19-treatment-results
Fauci: "What we've seen over the last several days is a spike in cases
that is way beyond the worst spikes that we have seen.
We've got to get that under control, or we risk an even greater outbreak in the U.S..
In the U.S., even in the most strict lockdowns, only about 50% of the country locked down
-- that allowed for the perpetuation of the outbreak, which we never did get under very good control."
https://www.bbc.com/news/live/world-53230784
Controlled Human Infection Models (CHIMs) are inappropriate for COVID-19
CHIMs require infecting healthy persons with a well-characterized microorganis
in order to study pathogenesis, characterize the immune response,
and elucidate the efficacy of vaccines or therapeutics. By design,
the controlled nature of CHIMs limits their generalizability
for predicting the effectiveness of a vaccine candidate against natural exposure.
A model of disease in healthy young volunteers may have questionable scientific validity
when extrapolated to older or other at-risk populations that have disproportionate morbidity.
Moreover, correlates of protection from SARS-CoV-2 are poorly understood
and may vary with the population or the vaccine construct.
Virtually all recent CHIMs have involved microorganisms that either
pose minimal risk for causing severe disease in the enrolled population,
have effective oral treatments, or both. Currently,
we lack sufficient knowledge of SARS-CoV-2 pathogenesis
to inform inclusion and exclusion criteria for a SARS-CoV-2 CHIM.
A single death or severe illness in an otherwise healthy volunteer
would be unconscionable and would halt progress.
https://www.nejm.org/doi/full/10.1056/NEJMp2020076
Kids and COVID-19: what we know, what we kind of know,
and what we need to do to know more.
They are less likely to contract the disease, and if they do contract it,
they are more likely to have a mild or asymptomatic case.
Death rates are much lower.
Children seem to transmit the virus less than do adults.
Data from the Netherlands suggest that
children are relatively unlikely to be the first case in a family cluster.
School staff are not more likely than other occupations to contract the disease.
Preschool and high-school teachers are actually less likely to get COVID-19.
The highest-risk group here is drivers - of taxis and buses in particular.
https://www.theatlantic.com/ideas/archive/2020/07/parents-need-facts-kids-covid-19/613744/
Computationally designed multi-epitope vaccine using spike glycoprotein of SARS-CoV-2
[ an epitope is the specific piece of the antigen to which an antibody binds ]
https://www.nature.com/articles/s41598-020-67749-1
Jul 1, 2020
Experimental coronavirus vaccine INO-4800 developed by Inovio Pharmaceuticals
shows promise and found to be safe in early-stage human trial
One of 17 vaccines being tested in humans and part of Operation Warp Speed,
it induced immune responses in 34 of the 36 healthy volunteers aged 18 to 50 years.
Most of the 10 patients with side-effects experienced only redness at the site of the shot.
"This may be the safest vaccine among other platforms being used against COVID-19,"
said Chief Executive Officer Joseph Kim.
U.S. Phase 2/3 efficacy study is to begin this summer.
https://www.livescience.com/face-mask-visualization-droplets-covid-19.html
At about 550,000 each day, U.S. viral test demand is again outpacing supply.
Quest said that orders for COVID-19 testing had grown by 50% in 3 weeks,
its systems were overwhelmed and it can now deliver COVID-19 test results in 1 day only for
hospitalized patients, patients facing emergency surgery, and symptomatic health-care workers.
Everyone else now must wait three to five days for a test result.
https://newsroom.questdiagnostics.com/COVIDTestingUpdates
"We hit the wall three weeks ago,"
said Jon Cohen, executive chairman of BioReference Laboratories.
In mid-June, four changes hit all at once, Cohen said.
Large companies began to test their employees en masse,
hospitals started to test every patient who needed an elective procedure,
and nursing homes started regularly testing employees and some residents.
The public also seemed to seek out voluntary tests in greater numbers.
"Our modeling efforts more or less show that, if you don't get results back in a day or so,
outbreaks really can't be stopped without isolating and quarantining all contacts preemptively."
https://www.theatlantic.com/science/archive/2020/06/us-coronavirus-testing-could-fail-again/613675/
Common human respiratory coronaviruses infections are highly seasonal
For 10 years, researchers from the University of Michigan (UM) School of Public Health
have tracked occurrences of 4 types of human coronaviruses (OC43, 229E, HKU1, and NL63)
in 890 to 1,441 individuals from 209 to 340 participating households and now track SARS-CoV-2.
When year-round surveillance was in place, most coronaviruses cases were detected
between December and April/May and peaked in January/February.
Only 2.5% of cases occurred between June and September.
New York, New Jersey and Connecticut on Tuesday expanded travel advisories
requiring people arriving to 16 southern and midwestern states to quarantine for 14 days:
Alabama, Arkansas, Arizona, California, Florida, Georgia, Iowa, Idaho, Louisiana,
Mississippi, North Carolina, Nevada, South Carolina, Tennessee, Texas and Utah.
The WHO has set a COVID-19 vaccine benchmark of 70% efficacy and protection for 1 year,
while 50% efficacy for 6 months is being cited by the FDA, which previously granted
emergency use authorization for hydroxychloroquine and chloroquine to treat COVID-19 based on nothing.
Full FDA approval traditionally requires 30,000 people enrolled in a Phase III clinical trial.
Estimates want a vaccine at least 70% effective to halt virus spread,
if given to 60% of the population within 90 days of an outbreak starting.
New research from Karolinska Institutet and Karolinska University Hospital shows that
many people with mild or asymptomatic COVID-19 demonstrate so-called T-cell-mediated immunity to it,
even if they have not tested positively for antibodies.
"One interesting observation was that
it wasn't just individuals with verified COVID-19 who showed T-cell immunity
but also many of their exposed asymptomatic family members.
Moreover, roughly 30% of the blood donors who'd given blood in
May 2020 had COVID-19-specific T cells,
a figure that's much higher than previous antibody tests have shown."
https://medicalxpress.com/news/2020-06-immunity-covid-higher-shown.html
How severe is the pandemic where you live?
Counties with fewer than one daily new case per 100,000 is green.
One to 10 is yellow; between 10 and 25 is orange; and above 25 puts you in the red.
"When you get into that orange and red zone it means, in all likelihood,
you're seeing a lot of velocity, a kind of fast upward trend"
a potential therapy
"We learned that the way natural killer cells identify cancer cells
is by recognizing the expression of stress antigens.
Well, it turns out virally infected cells express similar stress antigens."
Takeda's Morabito on the science behind plasma-based treatments
Takeda, CSL Behring and an alliance of plasma specialists are working on
a hyperimmune globulin, a purified version of convalescent plasma, for COVID-19 infection.
"With coronaviruses, there is experience with SARS and MERS
that hyperimmune approaches are effective, though none was developed for either disease
because the disease stopped having pandemic potential before development could be completed."
New Jersey Gov. Phil Murphy announced the state has postponed the start of indoor dining indefinitely.
It was originally scheduled to resume Thursday. Murphy cited instances of
'knucklehead behavior' at local outdoor restaurants among the reasons for the postponement.
https://www.cnn.com/2020/06/29/us/new-jersey-indoor-dining-trnd/index.html
Coronavirus and cancer hijack the same parts in human cells to spread:
Existing cancer drugs could fight COVID-19.
Viruses take control over many kinases to produce more viruses.
Of 97 kinases tested, coronavirus affects 49.
Of 87 existing drugs that change the kinase-controlled pathways used by the coronavirus,
several were effective in killing the virus in cells. A few
- silmitasertib, gilteritinib, ralimetinib, apilimod and dinaciclib - are either approved for treatment,
in clinical testing or under preclinical development for various diseases.
https://sciencex.com/news/2020-06-coronavirus-cancer-hijack-human-cells.html
Senhwa Biosciences Silmitasertib Named as Potential COVID-19 Therapy
Pharmacologic inhibition of p38, CK2, CDKs, AXL and PIKFYVE kinases
possess antiviral efficacy,
representing potential COVID-19 therapies.
68 drugs and compounds were tested, with antiviral efficacy found for several, including
silmitasertib, gilteritinib, ARRY-797, MAPK13-IN-1, SB203580, ralimetinib, apilimod, and dinaciclib, among others.
Harvard public health experts said the nation's COVID-19 epidemic is getting "quite out of hand"
and that, with cases rising rapidly in the hardest-hit states and a two-week lag
between infection and hospitalization, the situation appears set to worsen quickly.
"The increases that we're seeing right now have the capacity to cause far more disease in the future,"
said William Hanage, associate professor of epidemiology at the Harvard T.H. Chan School of Public Health.
https://medicalxpress.com/news/2020-06-pandemic-threatens-veer-states-health.html
A study from researchers at La Jolla Institute for Immunology and Erasmus University Medical Center
shows that
even the sickest COVID-19 patients produce T cells that help fight the virus.
"Activating these cells appears to be at least as important as the production of antibodies,"
says Erasmus MC Virologist Rory de Vries, Ph.D., who co-led the study.
States that have paused reopening plans include
Arizona, Arkansas, Delaware, Idaho, Louisiana, Maine, Nevada, New Mexico, and North Carolina.
Florida, Texas, and California have gone one step further
by putting back in place previous restrictions due to surging coronavirus cases.
Coronavirus mutation has taken over
When the first coronavirus cases in Chicago appeared in January,
they bore the same genetic signatures as a germ that emerged in China weeks before.
By May, a mutation associated with outbreaks in Europe and was found in 95% of all the genomes sequenced.
Of approximately 50,000 genomes of the new virus that researchers worldwide have uploaded to a shared database,
about 70% carry the mutation, officially designated D614G. The mutation doesn't appear to make people sicker,
but a growing number of scientists worry that it has made the virus more contagious.
https://www.sfgate.com/news/article/Coronavirus-mutation-has-taken-over-the-world-15373472.php
Superspreaders are created when large numbers of people gather close together,
don't practice social distancing or wear masks.
This allows for the efficient transfer of aerosolized droplets
that can remain airborne for 8-14 minutes from simply talking in an enclosed space,
and potentially up to 3 hours according to recent studies.
https://www.researchsquare.com/article/rs-29548/v1
Researchers work to develop cloth that could inactivate or repel coronaviruses
Polyester material is printed with alternating spots of silver and zinc resembling polka dots
one to two millimeters wide and spaced one millimeter apart.
This "electroceutical" material functions as an ordinary fabric when dry, but if dampened
- say, with saliva, vapor from a coughed up droplet or other bodily fluids -
ions in the liquid trigger an electrochemical reaction.
The silver and zinc then generate a weak electric field that zaps pathogens on the surface.
A study posted on the preprint server ChemRxiv reported that
its electroceutical fabric destabilized a coronavirus strain that causes
a respiratory illness in pigs and on an unrelated type of pathogen called a lentivirus,
leaving them unable to infect cells.
Metal dots are not the only potential approach.
Polytetrafluoroethylene (PTFE) nanoparticles in a solvent thermally sintered to polypropylene (PP) microfibers
create a robust, low-surface-energy, multilayer, and multilength scale rough surface
that repels bodily fluids, proteins, bacteria, one strain of adenovirus
that causes respiratory illness and another that causes conjunctivitis.
https://pubs.acs.org/doi/10.1021/acsami.9b23058
Students must return in whatever way possible,
NJ Education Commissioner Lamont O. Repollet said.
"Too many parents feel that remote-only instruction isn't working for their child,
and too many children are falling behind," said Repollet.
"It is becoming abundantly clear that children need to return to a school environment in some capacity,
and we need to do so safely. This is a matter of educational growth, and it's a matter of equity."
When possible, windows should be open to promote maximum air circulation.
School systems will have wide latitude in exactly what school looks like in the fall,
but must meet minimum guidelines.
"The window is closing,"
U.S. health and human services secretary Alex Azar told Meet the Press.
"We have to act, and people as individuals have to act, responsibly.
We need to social distance, we need to wear our face coverings."
https://www.ft.com/content/6eea1032-4ce6-4209-9242-bffbfae17eb3
U.S. sets another single-day record for new coronavirus cases.
As cases surge in parts of the U.S., testing centers have been overwhelmed
with an influx of patients, leading to long wait times and huge lines.
About 70% of U.S. residents say they plan to get a coronavirus vaccine
if it's free and available, according to a Washington Post-ABC News poll.
About two-thirds said the same in a CNN poll.
CNN asked Fauci whether a vaccine that is 70 to 75% effective
and given to two-thirds of the country would create herd immunity.
"No - unlikely," he responded.
https://www.washingtonpost.com/nation/2020/06/28/coronavirus-live-updates-us/
U.S. tops 2.5mn virus cases as infections surge
On Saturday alone the U.S. recorded more than 43,000 new cases,
according to a tally by Johns Hopkins University.
U.S. deaths now exceed 125,000, approximately one-fourth the world total of over 495,000.
https://medicalxpress.com/news/2020-06-tops-25mn-virus-cases-infections.html
Using data collected from around the world by Johns Hopkins University,
Binghamton University, State University of NY researchers have built
several prediction models that take advantage of artificial intelligence to examine trends
and patterns from 50 countries where coronavirus infection rates are highest,
including the U.S., and can often predict within a 10% margin of error
what will happen for the next three days based on the data for the past 14 days.
https://bitbucket.org/rrausha1/covid-19-case-prediction/src/master/model/
Ensemble Regression Models for Short-term Prediction of Confirmed COVID-19 Cases
https://find.cs.binghamton.edu/paper/COVID-prediction.pdf
"The main utility of this study is to prepare hospitals and healthcare workers"
https://www.youtube.com/watch?v=ExD4jtkb9VI
U.S. coronavirus cases surge by more than 45,000 in one day, total surpasses 2.5 million
Cases are growing by 5% or more based on a seven-day average in 34 states across the U.S.
States with largest case increases over last week:
"not just more new cases but also increases in hospitalizations
and in the percentage of tests that are coming up positive."
https://www.washingtonpost.com/coronavirus/
While states that reopened early and with few precautions
now grapple with case surges,
Philadelphia, Pittsburgh, and other cities across the country have not seen the sharp, sustained spikes
that were predicted after hundreds of thousands protested against police brutality.
With a 2 week COVID-19 incubation period, fallout should be clear by now.
The leading theory to explain this paradox is that being outdoors is safer than indoors.
Numerous studies support this. Japanese researchers, for example,
found coronavirus transmission indoors about 19 times greater than in the open air.
https://www.medrxiv.org/content/10.1101/2020.02.28.20029272v1
A new study funded by the National Bureau of Economic Research
https://www.nber.org/papers/w27408.pdf
offers another explanation: protests prompted an overall increase in people staying home,
which mostly offset any impact of transmission among protesters.
Point of no return: COVID-19 and the U.S. healthcare system An emergency physician's perspective
COVID-19 is a slow-moving mass casualty incident (MCI).
An MCI occurs when available local resources, such as personnel and equipment,
are overwhelmed by the number and severity of casualties.
https://advances.sciencemag.org/content/6/26/eabc5354
Fauci: contact tracing is 'not going well'
CDC Director Dr. Robert Redfield testified that about 27,000 or 28,000 people
are doing contact tracing work across the country.
He later estimated the necessary workforce to be about 100,000 tracers.
Former CDC Director Dr. Tom Frieden thinks the country will need even more, up to 300,000.
https://www.cnbc.com/2020/06/26/coronavirus-contact-tracing-is-not-going-well-fauci-says.html
DIY COVID-19 vaccine
A
May Science paper showed that a DNA vaccine seemed to provoke
an immune response against SARS-CoV-2. Researchers developed multiple vaccines
expressing different forms of the virus' spike protein and tested them in monkeys.
Josiah Zayner and collaborators in Mississippi and Ukraine want to reproduce
that experiment in themselves and livestream the process over several weeks.
The scheme, dubbed Project McAfee, after the antivirus software,
is possible thanks to the availability of new tools and technologies
- including viral DNA - to the general public.
The same spike protein used by researchers in their vaccine was ordered
from a DNA synthesis company, having it put in a solution that could be injected.
Test frequency matters more than test sensitivity for stopping outbreaks
Surveillance testing done every 14 days would allow the total number of infections
to climb almost as high as if there were no testing at all.
https://www.medrxiv.org/content/10.1101/2020.06.22.20136309v1
; UV need
Initially reluctant to allow cities and counties to require residents to wear face coverings,
TX governor gave them permission last week and
amid record increases this week began to encourage Texans to wear them.
University of Texas at Austin researchers have developed a prototype sensor
to simultaneously test for and distinguish between influenza and COVID-19.
Graphene over electrolyte gated field-effect transistors is extremely sensitive
to anything with a charge, including biomolecules such as viruses.
"It became clear that just by changing the antibody, we could pivot the platform to focus on the coronavirus"
https://phys.org/news/2020-06-sensor-coronavirus-flu-simultaneously.html
Oral rinses that could damage or destroy the lipid envelope may have the potential
to reduce the viral load of SARS-CoV-2 in the mouth and oropharynx.
https://www.nature.com/articles/s41432-020-0099-1
A COVID-19 pandemic guideline in evidence-based medicine
Based on the results of this study, non-pharmaceutical interventions,
including strict social isolation and distancing measures,
might reduce the spread of the SARS-CoV-2 by nearly 99.3%
(reproduction number mitigating from 406 to 2.5 in 30 days).
https://www.nature.com/articles/s41432-020-0105-7
Australia starts testing blitz to curb Melbournecoronavirus surge
30 new COVID-19 infections reported in the city overnight
for the 10th straight day of double-digit new cases in Melbourne and surrounding Victoria state.
Around 200 soldiers were deploying to Melbourneover the weekend
to help with the testing offensive in 10 suburb "hot spots", where officials are going door-to-door to track the virus.
Victoria Premier Daniel Andrews has set a goal of testing 100,000 people in 10 days in the targeted suburbs.
Around 20,000 tests were carried out in the first 24 hours of the effort.
https://medicalxpress.com/news/2020-06-australia-virus-blitz-curb-surge.html
Far-UVC light (222 nm wavelength) penetrates neither eyes' tear layer nor skin's outer dead-cell layer,
so it cannot damage living cells in the body,
but researchers found it killed more than 99.9% of the virus with a very low exposure.
Continuous exposure to far-UVC light at the current regulatory limit is estimated to kill
90% of airborne viruses in about 8 minutes, 95% in about 11 minutes, 99% in about 16 minutes, and 99.9% in about 25 minutes.
https://www.nature.com/articles/s41598-020-67211-2
[ 222 nm LEDs cost 7 cents each in large quantities
https://gmkjled.en.made-in-china.com/product/lFkECbcKAmhR/China-222nm-UVC-LED-for-Sterilize.html ]
COVID-19 and the Need for Health Care Reform
The patchwork way U.S. governs and pays for health care is unraveling in this time of crisis,
leaving millions of people vulnerable and requiring swift, coordinated political action
to ensure access to affordable care.
https://www.nejm.org/doi/full/10.1056/NEJMp2000821?query=featured_coronavirus
The air cooling system used in a German slaughterhouse,
aimed at keeping temperatures at a cool 6-10 degrees Celsius
but continually recycling the same untreated air into the room,
helped spread the coronavirus among hundreds of workers,
a hygiene expert said Wednesday,
a day after the mass outbreak triggered renewed lockdowns in the area.
"The technology is there" to fix the problem, he said, pointing to
high-performance mobile air filters that remove pollutants
or the microbe-killing UV lights that are used in hospital air conditioning systems.
https://medicalxpress.com/news/2020-06-abattoir-cooling-virus-german-expert.html
SC protests halted by COVID-19: 4 organizers, 6 protesters, 3 photographers infected
demonstrators who marched in Columbia, S.C., between May 30 and June 17 tested positive
[ long article also covers other pandemic-related news ]
About an hour after top public health officials denied that President Trump had ordered a slowdown in COVID-19 testing,
news broke that the federal government was winding down support for
local testing sites in states like Texas that continue to break daily case records.
Dallas County, which has the second-highest number of cases in the state,
will lose federal assistance at two testing sites, according to Rocky Vaz, director of emergency management.
The city of Dallas would end up paying between $130 and $150 per test once federal help ends.
Each site can perform 1,000 COVID tests per day.
https://www.thedailybeast.com/texas-hits-new-covid-19-record-as-feds-bail-on-test-funding
Herd immunity model accounting for population heterogeneity
Classic herd immunity HC is 60% immunization for homogeneous populations and R0 = 2.5:
HC = 1 - 1/R0
Considered heterogeneously, e.g. with more vs less interactions within population segments,
then immunities level HD within those differentiated herds can be lower,
e.g. HD = 43% for R0 = 2.5.
Varying interactions between segments further differentiates immunity levels.
https://science.sciencemag.org/content/early/2020/06/22/science.abc6810
[ arguably, this is equivalent to establishing different R0 values for the same disease
within and between various cohorts ]
Three monoclonal antibodies (mAbs) found to show neutralizing activities against SARS-CoV-2.
One, named 4A8, exhibits high neutralization potency against SARS-CoV-2,
but not at the receptor binding domain (RBD) targeted by most proposed vaccines.
https://science.sciencemag.org/content/early/2020/06/19/science.abc6952
While coronavirus cases are increasing in Northern California,
Dr. Vanessa Walker said fewer people are dying from the disease,
partly because of
three treatment methods:
* Administering steroids
* Avoiding intubation
* Using remdesivir
Around 5% of COVID-19 cases progress to acute respiratory distress.
Ruxolitinib, a drug originally used in cancer treatment,
inhibits enzymes in the body involved in excessive inflammatory reactions.
"It turned out well in the end for all patients who received the cancer drug
for longer than one week"
https://medicalxpress.com/news/2020-06-cancer-drug-covid-patient-acute.html
Gilead Sciences plans to start clinical trials for an inhaled version
of the antiviral remdesivir for the treatment of COVID-19, company officials said Monday.
"For patients who are at high risk of disease progression,
it could be particularly beneficial to start treatment outside the hospital"
https://stories.gilead.com//articles/an-open-letter-from-daniel-oday-june-22
Sanofi to invest $425 million expanding its vaccine development venture
with U.S. start-up Translate Bio to find an COVID-19 vaccine by next year. "We believe that
adding this mRNA platform to our vaccines development capabilities
will help us advance prevention against current and future infectious diseases"
https://medicalxpress.com/news/2020-06-sanofi-vaccine-venture-covid-.html
A trawl through a monkey genome using CRISPR-Cas9 genome-editing has newly identified
a handful of genes that code for several proteins, including some in the TGF-B signaling pathway,
which might be helping this novel coronavirus infect patients.
https://www.biorxiv.org/content/10.1101/2020.06.16.155101v1
Issues with Trump-touted 5-minute Abbott Laboratories COVID-19 test
106 reports of adverse events for the Abbott test, a staggering increase.
Among over 100 diagnostic tests receiving FDA emergency use authorization,
no other point-of-care test has received an adverse event report.
By some estimates, 10% of infected cause 80% of new infections.
In early March, a 57-year-old pastor and his wife, who both felt fine,
attended a series of church events over three days,
and the pastor returned for an additional Bible study group a few days later. Soon after,
they each started developing symptoms and eventually tested positive for the coronavirus.
At least 33 of the other 92 event attendees later tested positive for COVID-19,
and three of them died. These cases then spawned more than two dozen others.
23 states are reporting a rise in new cases and some continue to break records
in their daily reported cases. In the South, officials say more young people are testing positive.
"if widespread testing was the entire reason for the rise in cases,
you'd expect to see the proportion of positive tests go down
or at the very least remain steady. We're not seeing that"
https://www.cnn.com/2020/06/22/health/us-coronavirus-monday/index.html
China's Clover Biopharmaceuticals has initiated a phase 1 clinical trial of COVID-19
vaccine candidate SCB-2019 in Australia with adjuvants from GlaxoSmithKline and Dynavax.
It is expected to enroll 150 patients, with preliminary results in August
and a global phase 2/3 trial beginning by the end of the year.
Different post-confinement scenarios explored using a stochastic modified
SEIR (susceptible-exposed-infectious-recovered) model
that accounts for the spread of infection during the latent period
and also incorporates time-decaying effects due to potential loss of acquired immunity,
people's increasing awareness of social distancing, and non-pharmaceutical interventions.
https://www.nature.com/articles/s41562-020-0908-8
New York City's effort to stop the spread of the coronavirus through contact tracing
has been hampered by the reluctance of many people who are infected with the virus
to provide information to tracers.
https://medicalxpress.com/news/2020-06-nyc-virus-bumpy.html
Dexamethasone, recently shown to reduce coronavirus death risk by up to 1/3,
is being hoarded.
"We are already seeing hoarding behaviors and lack of availability of the product because of it"
Jun 21, 2020
Unlisted biotech firm CureVac launches German trials of another mRNA vaccine
First meaningful results of the trial with 168 participants could be available in 3-4 months.
Other messenger RNA vaccine developers include BioNTech, Moderna, and Translate Bio.
CureVac said in a press conference on Wednesday that
a similar vaccine it is developing against rabies can be stored for a year,
and the new vaccine would likely have the same properties.
Storage at room temperature is a likely option, the group added.
Combining recent methods of fast nucleic acid amplification to screen for SARS-CoV-2
with rapid RNA extraction cuts total detection time to 3.5 minutes from swab to diagnosis.
"[Polymerase chain reaction], a common methodology in research and clinical laboratories,
is slow, but sensitive. Antigen-based testing is fast, but not very sensitive.
Our technique is both fast and sensitive."
SARS-CoV-2 was found to be less stable at higher humidity and warmer temperatures.
Infectious virus was detectable for 12-48 hours, depending on the environmental conditions.
Half-life was significantly shorter at 27-degrees C/85% RH than 21-degrees C/40% RH or 4-degrees C/40% RH.
https://wwwnc.cdc.gov/eid/article/26/9/20-2267_article
How States With Rising Coronavirus Cases Are Responding
Oregon Governor Kate Brown, a Democrat, and Utah Governor Gary Herbert, a Republican,
have each paused their state's phased reopening plans in response to the increases.
But other Republican governors - Ducey in Arizona, Greg Abbott in Texas, and Ron DeSantis
in Florida among them - have refused to reimpose economic restrictions or social-distancing mandates,
in many cases frustrating local leaders, whose hands are tied.
https://www.theatlantic.com/politics/archive/2020/06/covid-resurgence-governors/613171/
Empatica, a spinoff out of MIT's Media Lab,
inked an agreement
with the U.S. Biomedical Advanced Research and Development Authority (BARDA) to help prove
its wearable sensors and algorithms could work against the coronavirus pandemic.
Its medical-grade Aura smartwatch will be tested in the real-world setting, worn by
frontline healthcare workers for 30 days and matched up with daily COVID-19 swab tests.
The goal is to spot the earliest possible signs that the virus is active and multiplying,
with the potential to be spread to others before a person shows respiratory symptoms.
In the 1970s, science-fiction writer Brian Aldiss coined the term "cozy catastrophe"
The classic cozy catastrophe doesn't take long and isn't lingered over;
the people who survive are always middle class
and have rarely lost anyone significant to them. https://tvtropes.org/pmwiki/pmwiki.php/Main/CosyCatastrophe
Comparing and contrasting SARS-CoV-2 vaccine trials
Operation Warp Speed aims start vaccinating millions of Americans in October
and offer shots to 300 million people in the U.S. by January 2021
using vaccine from candidates selected by an opaque process
test at pre-established sites not necessarily experiencing appreciable infection rates.
Open to products from every country, WHO Solidarity's efficacy trials
propose testing vaccine candidates prioritized by publicly detailed criteria
using vaccination teams that can quickly mobilize to localized outbreaks.
Beijing-based Sinovac Biotech is collaborating with the Butantan Institute,
a major research institution in Sao Paulo that manufactures vaccines,
to stage efficacy trials of its vaccine candidate in Brazil, where the COVID-19 epidemic is now raging.
https://science.sciencemag.org/content/368/6497/1295
Mobile symptom tracking
Taking advantage of existing longitudinal health care and research patient cohorts,
Drew et al. pushed software updates to about 2 million participants
encouraging potential COVID-19 symptom reports.
As exemplified by data from Wales, United Kingdom,
mathematical modeling predicted geographical hotspots of incidence
5 to 7 days in advance of official public health reports.
https://science.sciencemag.org/content/sci/early/2020/05/04/science.abc0473.full.pdf
The FDA has joined the
COVID-19 Diagnostics Evidence Accelerator, which will
collaborate with test manufacturers, technology companies, government and academic researchers,
as well as professional societies, payers, and health systems
to provide real-world analyses evaluating the performance of both PCR and antibody tests
- presented alongside coronavirus surveillance trends
and research into the disease's symptoms, progression and potential immunity -
as a companion project to the groups' Therapeutic Evidence Accelerator.
https://www.focr.org/
COVID-19 patients with extremely high levels of the stress hormone cortisol in their blood
are more likely to deteriorate quickly and die, according to new research published today.
Those with a baseline cortisol level of 744 or less survived on average for 36 days.
Patients with levels over 744 had an average survival of just 15 days.
https://medicalxpress.com/news/2020-06-high-cortisol-greater-death-covid-.html
China has found the trading sections for meat and seafood in Beijing's wholesale food market
to be severely contaminated with the new coronavirus and
suspects the area's low temperature and high humidity may have been contributing factors
Elizabeth Warren: 'Egregious' Conflicts of Interest in Trump's COVID-19 Response
Both Slaoui, chief adviser to Operation Warp Speed, and Short, Pence chief of staff,
have key roles in the coronavirus response effort while holding stock in companies
whose values could soar from the development of a COVID-19 vaccine,
according to public reporting and financial disclosures.
Dealing with COVID-19 at home
Limit your direct exposure
"Make sure they are hydrating and eating."
check for inadequate oxygen levels
if asymptomatic, you don't need to get tested
https://medicalxpress.com/news/2020-06-covid-home.html
Good news: people don't necessarily believe pandemic misinformation...
Bad news: they don't necessarily believe valid information, either.
Just over a quarter of those surveyed claimed to have read or seen
a set of invented headlines that had not appeared widely on social media.
This suggests that accurate recall of misinformation is less than 10%.
Between 20 and 25% of respondents judged fake claims to be true.
Almost 60% either identified true information as false or were not sure.
https://blogs.scientificamerican.com/observations/good-news-and-bad-news-about-covid-19-misinformation
Coronavirus in Trump country Case rate increases are NOT generally being driven by test rate increases: time wounds heels:
N95 shortage - FEMA report: "[t]he demand for gowns outpaces current U.S. manufacturing capabilities";
the government plans to continue into July asking medical staff to reuse N95 masks and surgical gowns
intended to be disposed of after one use .
https://www.hassan.senate.gov/imo/media/doc/SCTF%20Demand%20PPE%20Chart.pdf
3p21.31 gene cluster identified as a genetic susceptibility locus in COVID-19 patients with respiratory failure;
ABO blood-group system involvement confirmed https://www.nejm.org/doi/full/10.1056/NEJMoa2020283
free online risk calculator; take melatonin
[6/16 USAfacts data delay allowed collecting more 6/17 news]
Using data from nearly 12,000 patients enrolled in Cleveland Clinic's COVID-19 Registry,
which includes all individuals tested at Cleveland Clinic for the disease,
not just those that test positive.
Patients actively taking melatonin (over-the-counter sleep aid),
carvedilol (high blood pressure and heart failure treatment)
or paroxetine (anti-depressant) are less likely to test positive than others.
[ melatonin reduces my result from~1.8 to 1.35%; Risk calculation may take a few minutes to report: ] https://riskcalc.org/COVID19
Dexamethasone, a cheap, widely available corticosteroid,
significantly reduced deaths of severely sick COVID-19 patients in a major clinical trial.
They did not find any benefit in patients not receiving respiratory support.
Dexamethasone's effect is seemingly much stronger than that of remdesivir.
Although full trial data have not yet been released,
several outside commentators hailed the result as a "breakthrough."
https://www.bbc.com/news/health-53061281
When coupled with a nucleic acid extraction method,
Hibergene's freeze-dried fast molecular reagent system provides sensitivity equivalent to that of current PCR systems
for samples from individuals at all stages of COVID-19 infection.
https://www.hibergene.com/products/respiratory/hg-covid-19/
[Old too soon]
"those aged under 20 years are roughly half as susceptible to infection as those over 20 years of age,
and 79% of infections are asymptomatic or paucisymptomatic (that is, subclinical)
in 10- to 19-year-olds, compared with 31% in those over 70 years of age."
https://www.nature.com/articles/s41591-020-0962-9/tables/1
About half of hospitalized coronavirus patients experience neurological symptoms including dizziness,
difficulty concentrating, a loss of smell and taste, seizures, strokes, and weakness,
according to a new review of research published in the Annals of Neurology.
https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25807
Human trials begin for Imperial College London self-amplifying RNA vaccine
300 healthy participants, aged between 18 and 70, will receive 2 doses over the coming weeks;
tests could then move on to 6,000 volunteers if there is an effective immune response.
https://www.imperial.ac.uk/news/198314/imperial-begin-first-human-trials-covid19/
Nine states - Alabama, Arizona, Florida, Nevada, North Carolina, Oklahoma, Oregon, South Carolina and Texas -
reported either new single-day highs or set a record for seven-day new coronavirus case averages on Tuesday,
according to a Washington Post analysis.
https://www.washingtonpost.com/nation/2020/06/17/coronavirus-live-updates-us/
New Zealand reported its first new cases of coronavirus in almost a month on Tuesday
when two recent arrivals from Britain tested positive
after being released early from quarantine to visit a dying relative.
https://medicalxpress.com/news/2020-06-zealand-virus-cases-days.htm
COVID-19 vaccine trials: "It's really complicated."
1) Populations that have high levels of viral transmission are a moving target.
Moderna's vaccine will enroll 30,000 people and take place
primarily at U.S. hospitals and universities
long used for HIV and flu vaccine testing
and now overseen by Warp Speed's COVID-19 Prevention Network.
But which of those brick-and-mortar sites will have enough SARS-CoV-2
circulating near them to quickly produce an efficacy signal is uncertain
given the shifting distribution of new cases in the U.S..
Beijing's Sinovac Biotech will stage efficacy trials of its vaccine candidate in Brazil,
where the COVID-19 epidemic is now raging.
2) Competition among trial efforts could hinder the global push.
"everybody loves to collaborate unless they want to win"
WHO has yet to announce its Solidarity test candidates, but,
unlike Warp Speed "which won't consider Chinese-made vaccines"
* it is open to products from every country, and
* publicized detailed criteria for how it will prioritize vaccines.
There are only 200 million vials left in the world because they've all been bought up.
One in 10 new drugs make it to market; the U.S. has funded only 2 for COVID-19.
An estimated $26 billion is needed to start producing the 10 most promising vaccines now.
Existing production facilities are highly specialized for making a single, specific type of vaccine,
like polio or measles, and they are currently reserved to make those vaccines.
If those facilities are repurposed to make a new COVID-19 vaccine,
it will put the supply of other critical vaccines at risk.
https://thehill.com/opinion/healthcare/502649-covid-19-vaccine-in-warp-speed
A third of hospitalised coronavirus patients develop dangerous blood clots.
The British Heart Foundation will test the theory the clots are caused by a hormone imbalance
triggered by coronavirus infection, using TRV027 to address that imbalance.
https://www.bbc.com/news/health-53045180
Europe reopens many borders but not to Americans, Asians
https://medicalxpress.com/news/2020-06-europe-reopens-borders-americans-asians.html
treatment should be based on 3 COVID-19 phases
1) the virus multiplies inside the body
and is likely to cause mild symptoms that may be confused with a common cold or flu.
2) the immune system becomes strongly affected by infection
with symptoms such as persistent cough, shortness of breath and low oxygen levels.
Problems with blood clotting may predominate.
3) hyperinflammatory phase: injury to the heart, kidneys and other organs
* Plasma containing antibodies from recovered COVID-19 patients (i.e., hyperimmune plasma),
which has been found to reduce the amount of live virus (viral load) in the early infection phase.
* Antiviral drugs, including remdesivir, which have helped interrupt viral replication in Phase 1
and may continue to be beneficial in Phase 2.
* Tissue plasminogen activator (tPA). A drug used to treat stroke,
tPA breaks up blood clots that may occur during Phase 2.
* Inflammation-fighting medications, including corticosteroids, tocilizumab and sarilumab.
These may help reduce system-wide inflammation in Phases 2 and 3.
* The anticoagulant (anti-clotting drug) heparin is important during any stage of the disease
to prevent blood clots in blood vessels and capillaries (micro- and macro-vascular thrombosis).
https://medicalxpress.com/news/2020-06-individualized-treatment-covid-patients-based.html
Natural History of Asymptomatic SARS-CoV-2 Infection: cruise ship Diamond Princess
712 persons infected among the 3711 passengers and crew members
410 (58%) of these infected were asymptomatic at the time of testing
- 96 of those were transferred to a hospital February 19 - 26.
11/96 developed symptoms in a median of 4 days,
with the risk of being presymptomatic increasing with age.
https://www.nejm.org/doi/full/10.1056/NEJMc2013020
Advice from a systems-biology model of the corona epidemics
"an initially intensive but adaptive lockdown strategy should be most efficient,
both in terms of its low number of casualties and shorter duration"
https://www.nature.com/articles/s41540-020-0138-8
Four main treatment classes are being explored to fight COVID-19
by either inhibiting the virus or modulating the body's response to it:
1) antiviral drugs, to inhibit viral replication;
2) immunomodulatory drugs, to dampen an immune system in overdrive;
3) neutralizing antibodies, to inhibit the virus and help the immune system clear the infection;
4) sera (the acellular fraction of circulating blood containing a wide range of antibodies,
cytokines and other immunomodulators) from patients who have recovered from COVID-19.
https://www.nature.com/articles/s41551-020-0579-9
Applying 8 multiparameter flow cytometry panels to peripheral blood from 63 hospitalized patients
yielded data strongly supporting the hypothesis that across a highly variable cohort,
a consensus COVID-19 immune signature was discernible.
The signature captured several aspects of previously reported COVID-19 immunophenotypes,
blending specific traits of vaccine responses and sepsis with less commonly cited traits.
https://www.medrxiv.org/content/10.1101/2020.06.08.20125112v1.full.pdf
TXA127 enzyme could protect lungs from COVID-19's worst symptoms
The first trial, sponsored by Columbia University, is slated to start this month,
enrolling 100 patients with moderate COVID-19.
https://www.statnews.com/2020/06/10/coronavirus-lungs-enzyme/
A noncompeting pair of human antibodies block COVID-19 virus binding to its receptor ACE2
Two antibodies, B38 and H4, blocked the receptor binding domain (RBD) of the viral spike protein
from binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2).
The B38-binding site overlaps with the binding site for ACE2.
Although H4 also blocks RBD binding to ACE2, it binds at a different site,
and thus the two antibodies can bind simultaneously.
https://science.sciencemag.org/content/368/6496/1274
COVID-19 and flu, a perfect storm(?) (editorial)
Almost nothing is known about the interaction of influenza virus and SARS-CoV-2.
The Southern Hemisphere influenza season, just beginning, may provide some clues.
Every effort should be made for combined COVID-19 and influenza testing.
Some enhanced influenza vaccines (e.g., high-dose inactivated vaccine and recombinant vaccines)
increase protection in older adults.
https://science.sciencemag.org/content/368/6496/1163
Jun 11, 2020
vaccine enhancement is bad; newly discovered graphics
Vaccine-induced enhancement rendered vaccinated subjects more susceptible to infection
rather than protecting them. Antibody-dependent enhancement (ADE) plays an important role.
https://www.sciencedirect.com/science/article/pii/S0264410X08015053
Phase 3 trials, which typically involve tens of thousands of people and measure
whether a vaccine is safe and effective, will begin with one by Moderna in July,
then an Oxford/AstraZeneca vaccine in August and one by Johnson & Johnson in September.
https://www.cnn.com/2020/06/10/politics/vaccine-trials-funding/index.html
The story of COVID-19: A comparative analysis
Using 7 models, SARS-CoV-2 virus was compared with
"other common human respiratory pathogens that are known to cause significant morbidity",
and showed "a modest interferon or antiviral response
but a longer and exuberant proinflammatory signal in the form of chemokines". https://en.wikipedia.org/wiki/Chemokine
This "makes a stronger case for directing therapeutic strategies
against the proinflammatory milieu rather than the more classical antiviral response."
https://stm.sciencemag.org/content/12/547/eabc8943
After peaking in April, U.S. epidemic new cases are a seemingly unending plateau
With more than 35,000 for several days in April,
new cases still have been regularly exceeding 20,000.
As of June 7, the U.S. had an average daily positivity rate of 14%,
well above the World Health Organization guideline of 5% over two weeks
before social distancing guidelines should be relaxed. Even if scaled up,
testing does very little good without finding and isolating those exposed.
https://www.cnn.com/2020/06/09/health/us-coronavirus-tuesday/index.html
Using mass spectrometry analysis, researchers at Berlin's Charite university hospital found
27 different proteins in blood samples from coronavirus patients being treated in the hospital,
with different levels correlating with the severity of their disease,
according to the World Health Organization's coding criteria for COVID-19.
"An early blood test would enable the treating physician to predict
whether or not a patient with COVID-19 will develop severe symptoms."
https://www.sciencedirect.com/science/article/pii/S2405471220301976
Sherlock Biosciences scales up CRISPR-based coronavirus diagnostic test manufacturing,
with 30,000 test kits by the end of this month,
by partnering with Danaher's Integrated DNA Technologies division,
which will supply Cas13a enzymes and template RNA needed to match up with genomic material specific to the novel coronavirus,
with CRISPR's gene-snipping action producing a detectable positive result.
Cancer immunotherapies adapted to identify 65 SARS-CoV-2 targets for vaccines
"A subset of the sequences selected in our study are derived from viral regions
that are very similar to other coronaviruses, and thus our approach, if successful,
could lead to protection against not only SARS-CoV-2
but also other coronaviruses that might emerge in the future."
https://www.sciencedirect.com/science/article/pii/S2666379120300483
"It may seem counterintuitive to focus on treatments,
not for the critically ill patient in need of a life-saving intervention,
but rather for the seemingly healthy patient shortly after a COVID-19 positive test.
Nonetheless, our analysis shows that the right early-stage antiviral treatment
can block transmission to others and, in the long run, may well save more lives"
https://www.nature.com/articles/s41467-020-16585-y
Sofosbuvir as a potential alternative SARS-CoV-2 treatment
The most highly conserved protein in all known RNA viruses is the viral monomeric RdRp.
Several drugs that bind to the RdRp active site are approved to treat RNA viral diseases,
including Remdesivir, recently proven effective blocking SARS-CoV-2.
Sofosbuvir (SOF) is a nucleotide analogue targeted against the HCV polymerase, NS5B.
Previous work shows SOF has in vitro and/or in vivo antiviral activity against other Flaviviruses.
SOF already has approval as a standard treatment and a well-known safety profile;
it would be interesting to develop in vitro experiments to test its efficacy against the SARS-CoV-2
https://www.nature.com/articles/s41598-020-66440-9
Detection of air and surface contamination in hospital rooms of infected patients
High touch surface contamination is shown in 10/15 patients in the first week
and 3/15 beyond the first week of illness.
Air sampling detects SARS-CoV-2 PCR-positive particles of sizes >4um and 1-4um
in 2/3 rooms, despite these rooms having 12 air changes per hour.
https://www.nature.com/articles/s41467-020-16670-2
Electrochemiluminescence (ECL) increases serological test sensitivity levels up to 128%
"...it relies on the enhancement of the signal as opposed to the enhancement of the target,
as usually happens with enzymatic methods or polymerase chain reaction"
Researchers refined mechanisms regulating ECL analyses and
employed those to develop more efficient serological test reactants.
https://www.nature.com/articles/s41467-020-16476-2
First open-source all-atom models of a full-length S protein,
which plays a central role in viral entry into cells,
a main target for vaccine and antiviral drug development.
CHARMM-GUI is described as a "computational microscope".
http://charmm-gui.org/?doc=demo&id=cov_2_s&lesson=1
Oxford Biomedica has signed Vaccines Manufacturing and Innovation Centre (VMIC)
to rapidly equip two new good manufacturing practice (GMP) manufacturing suites
for further scale up of AZD1222 from summer 2020. AstraZeneca has now taken over
global responsibility for manufacturing, development and distribution of AZD1222.
[U.K. evidently wants to ensure domestic vaccine manufacturing capacity]
SC testing BS
With reported positive case rising, a responsible government would increase testing,
but no; SC stopped reporting actual test counts 2 weeks ago,
when they amounted to less than 1/1,000 and presumably mostly among healthcare workers: Q:
What kinds of fools accept projections utterly at odds with previous trends? A: Lazy fools; positive case rates get more media attention than inflated test rates.
SC's positive test rate based on actual testing may be nearer 25% than 15%.
As previously noted, SC diverted federal pandemic funding
to pork barrels.
New Zealand eliminates coronavirus, lifts restrictions within the nation
With the announcement, New Zealand becomes one of the first countries to announce
domestic elimination of the virus after going 17 days without detecting a new case
within its borders and 12 days without a patient in hospital
The U.S. government's current supply of remdesivir,
the only drug proven to work against COVID-19, will run out at the end of the month.
A study showed it reduces hospital stays from 15 to 11 days.
Now that the free supply is almost gone, there are concerns Gilead will charge a high price.
https://www.cnn.com/2020/06/07/health/remdesivir-donation-runs-out-coronavirus/index.html
Italian researchers used whole exome sequencing (WES) to study the data from 130 patients
and uncover a number of common susceptibility genes that correlated with favourable or unfavourable outcomes.
"We believe that variations in these genes may determine disease progression.
To our knowledge, this is the first report on the results of WES in COVID-19."
https://medicalxpress.com/news/2020-06-identification-genetic-basis-covid-susceptibility.html
What this coronavirus does to your body that makes it so deadly
A coronavirus infection usually plays out one of two ways:
as a lung infection that includes some cases of what people would call the common cold,
or as an infection in the gut that causes diarrhea.
COVID-19 starts out in lungs like common cold coronaviruses,
but then causes havoc with the immune system. It has many more ways
than does influenza to stop cells from calling out to the immune system for help.
https://theconversation.com/what-the-coronavirus-does-to-your-body-that-makes-it-so-deadly-133856
What government should be doing
support large scale access to different drugs
that have shown they may be effective against the coronavirus
in a framework that enables collecting good information
to determine which medicines are working best for patients
advance treatments that help protect people from becoming infected in the first place
"Anything where there's a crowd of people,
without risk reduction strategies, it's a ten."
Most hazardous activity: Bars (risk level 9/10)
Lowest risk level: playing tennis; restaurant prepaid curbside pickup
COVID-19 and slow boiling frogs [including alt-right Pepe]
> I am working on another bar chart to compare estimated contagious populations today
> compared with 2 months ago, when lockdowns were being enforced.
As threatened, this plots most recent 20 days' reported cases,
presumed still sick and contagious (red),
compared with comparable counts from 60 days prior (yellow).
Among tracked counties:
CA, KY, VA, SC, and TX typically now have more sick...
A half dozen counties have the same now as then.
COVID-19 and slow boiling frogs [including alt-right Pepe]
https://en.wikipedia.org/wiki/Boiling_frog
"We're very concerned that our public health message isn't resonating,"
Robert R. Redfield said, noting that
some states are reopening their economies while local infections are still spreading,
and many Americans are ignoring the CDC's advice to wear masks.
The U.S. announced Thursday that it will require testing labs
to collect zip code data and demographics including race, ethnicity, sex and age.
The CDC funds as much as 70% of state and local public-health efforts.
Putting the Public Back in Public Health
"Although decisions to gradually reopen societies are ultimately based on
a complex calculus of political, economic, and public health considerations, it's clear that
there is a high unmet need for better estimates of communities' burden of COVID-19
to guide such decision making. Fortunately, some mobile symptom-surveillance tools
can be used for predictive modeling to address this critical priority."
https://www.nejm.org/doi/full/10.1056/NEJMp2016259
"... holding officials accountable for demonstrating that orders are reasonable and necessary
- has been a robust scaffold for assessing the legality of public health orders
for more than a century, since it was announced in the seminal Supreme Court case of
Jacobson v. Massachusetts. In addition to recognizing the need to give officials flexibility
to implement forceful public health interventions, Jacobson recognized that
administrative agencies are both nimbler and more expert than legislatures.
In upending this framework, the Wisconsin court did more than
disrupt settled understandings of the law: it hobbled the state's ability to save lives."
https://www.nejm.org/doi/full/10.1056/NEJMp2019662
https://en.wikipedia.org/wiki/Jacobson_v._Massachusetts
I am working on another bar chart to compare estimated contagious populations today
compared with 2 months ago, when lockdowns began. Meanwhile:
Hong Kong restaurateurs' 17-page "COVID-19 Playbook"
[ been there (SARS), done that ]
outlines highly specific and practical procedures,
from handwashing to face masks, hand sanitizer, cleaning procedures,
physical contact, temperature checks, health declaration forms,
cost management and how to communicate with concerned or disgruntled guests.
https://blacksheeprestaurants.com/covid/
Second-guessing Operation Warp Speed
The 5 selected vaccines rely on just 3 different technologies.
"They're the ones that are first because in many ways they're the fastest ones to make"
Inactivated, whole SARS-CoV-2 is the basis for 4 of 10 vaccines that have advanced to human trials around the world,
including one that worked well in a monkey study, but all 4 are Chinese.
Warp Speed explicitly would not consider any vaccines made in China.
Fauci on school reopening: "...it really depends on the level of viral activity,
and the particular area that you're talking about.
What happens all too often, understandably, but sometimes misleadingly,
is that we talk about the country as a whole in a unidimensional way."
https://www.cnn.com/2020/06/03/us/fauci-schools-reopening-coronavirus/index.html
Biomedical Advanced Research and Development Authority (BARDA) taps Evidation Health
to digitally monitor healthcare workers for early COVID-19 symptoms
https://evidation.com/news/evidationhealthandbardapartner/
"Evidation's data platform ingests over 1 trillion data points annually,
drawn from millions of participants across different disease areas,
and feeds them through a virtual study design and execution engine
that's compliant with federal privacy and research regulations and good clinical practices."
https://www.fiercebiotech.com/special-report/evidation-health
COVID-19 and Health Care's Digital Revolution
"Clinical workflows and economic incentives have largely been developed
to support and reinforce a face-to-face model of care,
resulting in the congregation of patients in emergency departments
and waiting areas during this crisis...
With the first emergency COVID-19 authorization,
Congress lifted provisions that limited telemedicine services to rural areas,
allowing the use of telemedicine services for all beneficiaries of fee-for-service Medicare."
https://www.nejm.org/doi/full/10.1056/NEJMp2005835
"nature": Coronavirus research updates
[depressed people judge their circumstances more realistically]
A general occurrence of unrealistic optimism was mainly observed in men
by all three measures but also women in the last two measures.
https://www.mdpi.com/2077-0383/9/5/1464/htm
Adaptive Immunity to SARS-CoV-2
SARS-CoV-2-reactive CD4+ T cells in ~40%-60% of unexposed individuals
suggest cross-reactive T cell recognition
between circulating "common cold" coronaviruses and SARS-CoV-2.
https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3
COVID-19 Lockdown Disrupts Internal Clocks
Psychologists "know" that time sense links to well-being,
with perceived slower passage signalling depression.
Research using this unplanned natural experiment
gauges psychological impacts of time distortions,
documenting sadness and boredom tied to an overall feeling of deceleration.
https://psyarxiv.com/efdq5/
Median incubation period is approximately 4-5 days before symptoms.
97.5% of symptomatic patients develop symptoms within 11.5 days.
Within 5-6 days of symptom onset, SARS-CoV-2 viral load peaks.
Severe COVID-19 cases progress to acute respiratory distress syndrome
(ARDS), on average around 8-9 days after symptom onset,
which is the cause of death in 70% of fatal COVID-19 cases.
What Do Infectious Disease Experts Know, When Did They Know It?
This 02 Apr article, written by hedge fund risk manager Aaron Brown,
attempts to monetize differences among epidemiologists' forecasts.
"asking where Las Vegas would set betting odds
on various pandemic outcomes, if all the customers were
infectious disease experts and experienced, successful gamblers
is my quick approach to estimating what the experts know"
"When we see bookies making profits around 5% or more,
as in the under 40,000 bet and the 80,000 to 160,000 bet,
we're probably looking at more disagreement than is reasonable."
Superforecasters: COVID-19
This group was cited in the previous article;
predictions have updated comments.
49% probability of 23-73 million U.S. cases by 31 Mar 2021
54% probability that FDA does not approve a treatment before 1 Jul 2021
37% probability that FDA does not approve a vaccine before 1 Apr 2022
https://goodjudgment.io/covid-recovery/#1384
re: famotidine
Faithful readers may recall from a month ago that,
motivated by anecdotal Chinese results for this common gastric acid suppression remedy,
Northwell Health used famotidine to reduce intubation and death rates from 22% to 10%.
https://www.medrxiv.org/content/10.1101/2020.05.01.20086694v2
This new paper attempts to sort how and why:
https://www.researchsquare.com/article/rs-30934/v1
"The most straightforward explanation of the apparent famotidine activity as a COVID-19 therapy
is that the drug acts via its antagonism or inverse-agonism of histamine signaling
and via its arrestin biased activation - all a result of its binding to [histamine] H2.
If true, then it is reasonable to infer that a SARS-CoV-2 infection
that results in COVID-19 is at least partially mediated by pathologic histamine release."
https://blogs.sciencemag.org/pipeline/archives/2020/05/29/famotidine-histamine-and-the-coronavirus
COVID-19 survivors typically have scads of SARS-CoV-2-specific antibodies,
but few effectively stop infection. Isolating a monoclonal antibody effective
against SARS-CoV-2 could yield a better treatment than convalescent plasma therapies.
Eli Lilly launched the first human safety trial of a monoclonal antibody against SARS-CoV-2.
https://www.the-scientist.com/news-opinion/first-antibody-trial-launched-in-covid-19-patients--67604
Snubbed by reopening Nordic neighbors, Swedish expert admits error
"If we would encounter the same disease, with exactly what we know about it today,
I think we would land midway between what Sweden did and what the rest of the world did,"
said Mr Tegnel
https://www.ft.com/content/dae6d006-9adc-46d5-9b4e-79a7841022e8
doctors' thinking has evolved: wear masks
"The practices that work are really the practices
that reduce the ability of respiratory droplets to easily travel to other people.
So that means that we've learned that it's not just the distance quotient or equation.
In fact, we've learned that sneezes and coughs can actually amplify beyond the six feet,
but, in fact, that masks are really effective. Ventilation is really important.
And the time interval that separates people from touching the same objects is important.
So making sure that we're not just washing hands but also not touching the same objects,
especially indoor objects, is the hallmark of effective distancing strategies."
https://www.newyorker.com/news/q-and-a/how-to-social-distance-as-america-opens-back-up
Celltrion, which conducted the study in collaboration with
South Korea's Chungbuk National University College of Medicine,
reports that its antibody treatment showed a rapid reduction of symptoms
followed by a remission of the disease in comparison with a placebo group.
It anticipates starting first clinical trials on humans in July.
"Celltrion is drawing on its expertise, innovation and previous experience in coronaviruses,
such as efforts researching the efficacy of CT-P38,
an investigational antibody to treat Middle East Respiratory Syndrome (MERS),
as well as CT-P27, a multi-antibody drug for influenza which is being tested in a phase 2b study,
to develop a safe and effective treatment for COVID-19."
"THE LANCET": Physical distancing, face masks, and eye protection
to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis
[ researchers reviewed data from 44 studies that assess distancing measures,
face masks and eye protection to prevent virus transmission between those with confirmed
or probable COVID-19, SARS or MERS infection and individuals close to them. ]
Keeping a distance of more than 1 meter from other people was associated with
3% risk for infection, compared with 13% for less than 1 meter
for every extra meter of distance up to 3 meters,
infection risk reduces by 1/2
face shields, goggles and glasses reduce infection risk by > 1/2
"lightly edited" transcript of Fauci interview
"You need a few months at least of having vaccinated individuals getting exposed.
So let's say it's July, August, September, October.
By November, you should have an efficacy signal.
If you do and you're already manufacturing doses, by December and January,
if you're lucky and if in fact it is effective,
you can have a significant number of doses available by the end of the year,
the beginning of 2021. So I think it's aspirational, but it's certainly doable."
[ my favorite COVID-19 article, so far...]
Icelandic studies: by sequencing the virus from every person infected,
researchers at deCODE could also make inferences about how it had spread.
"One of the very interesting things is that, in all our data,
there are only two examples where a child infected a parent.
But there are lots of examples where parents infected children."
over-all mortality in Iceland had actually gone down since the coronavirus had arrived.
https://www.newyorker.com/magazine/2020/06/08/how-iceland-beat-the-coronavirus
Billionaire scientist and businessman Patrick Soon-Shiong announced that
an experimental vaccine being developed by two of his companies
is
one of 14 candidates being evaluated by Operation Warp Speed,
despite not being on WHO's list of 125 candidates.
"fully human" monoclonal antibody (mAb) 47D11 prevents coronavirus from infecting cultured cells
47D11 neutralizes SARS-CoV and SARS-CoV-2 via a mechanism that is not known yet,
which is entirely different from receptor-binding interference.
"This cross-neutralizing antibody targets a communal epitope on these viruses
and may offer the potential for prevention and treatment of COVID-19,"
concluded the authors in their study published in Nature.
https://www.nature.com/articles/s41467-020-16256-y
COVID-19 Best Practices (159 pages)
[ last updated: May 29,2020; much seems already dated]
"There is currently no evidence that wearing a mask (medical or other types)
in the community setting can prevent infection with respiratory viruses,
including COVID-19, in a healthy person."
https://bestpractice.bmj.com/topics/en-us/3000168/pdf/3000168.pdf
20133 COVID-19 UK hospital patients
median age: 73
median duration of symptoms before admission: 4 days
41% recovered, 26% died, 34% continued receiving care (3 May 2020)
https://www.bmj.com/content/369/bmj.m1985
COVID-19: in the footsteps of Ernest Shackleton
"We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic.
Of the 217 passengers and crew on board,
128 tested positive for COVID-19 on reverse transcription-PCR (59%).
Of the COVID-19-positive patients, 19% (24) were symptomatic;
6.2% (8) required medical evacuation;
3.1% (4) were intubated and ventilated;
and the mortality was 0.8% (1).
The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients)."
https://thorax.bmj.com/content/early/2020/05/27/thoraxjnl-2020-215091
Model projects VA summer peak > 5000 new cases / day
Under a "light rebound", where Virginians' social interactions return to 1/6 of pre-pandemic levels,
the state's peak of new confirmed cases is projected to come during the week ending Aug. 9,
according to the latest UVA model, with 38,546 new confirmed cases for that week.
"this is not a respiratory illness alone, this is a respiratory illness to start with,
but it is actually a vascular illness that kills people through its involvement of the vasculature"
"[The virus] enters the lung, it destroys the lung tissue, and people start coughing.
The destruction of the lung tissue breaks open some blood vessels.
Then it starts to infect endothelial cell after endothelial cell,
creates a local immune response, and inflames the endothelium."
"Four or six months down the road, I suspect we'll have pretty good test strips that people will be able to buy like a pack
and test themselves every few days or if they're considering going back to school or work,"
David R. Walt, a diagnostics expert from Harvard Medical School and doctor at Brigham and Women's Hospital
https://www.cnbc.com/2020/05/08/cheap-rapid-at-home-testing-for-covid-19-could-take-weeks-or-months.html
Eleanor Murray, epidemiology professor at Boston University,
was dubious about how quickly the supply chain could accommodate this vision.
"The amount of those tests that would have to be manufactured for everyone to test every day would be astronomical"
Memorial Day weekend occupancy was between 75% and 90% in SC coastal communities;
occupancy is typically between 90% and 100% for Memorial Day weekend.
Hilton Head's bridge traffic was down 11-13%.
https://www.islandpacket.com/news/business/article243020666.html
For no particularly good reason (Bill Gates?), I feel more optimistic about
Moderna's mRNA
Since no mRNA vaccines have been approved,
there are lots of skeptics besides conspiracy theory tinfoil hats, so it will certainly get lots of scrutiny.
Germany, Vietnam, and New Zealand have reopened schools.
"The U.S. is notorious for not thinking it can learn from the world"
German students administer coronavirus tests on themselves every 4 days.
Vietnamese check temperatures before entering schools and wear masks.
New Zealanders can individually delay returning until they feel comfortable.
Only NY, KY, AK meet basic reopening criteria
bias
> Everybody has a bias and it clouds their judgement.
My bias is pessimistic, but
I agree that is important for schools to reopen and worth some risk.
What I suggested to my daughter for Northern VA schools,
is that they consider allowing kids capable of remote learning to do so,
freeing up some space to spread out those who cannot.
The other key would be aggressive tracing and quarantining of new cases.
Schools and parents would have to be prepared for students to be
removed from classes and isolated immediately on suspicion of infection.
I doubt whether many schools could open enough windows to adequately
circulate air, even if clothing to keep kids comfortable were available.
Most schools could never maintain HVAC filtration adequate to filter virus.
Probably a lot of teachers speaking thru masks could not be understood,
but even if teachers somehow avoided catching COVID-19 from asymptomatic kids,
too many of those kids will probably take the virus home and kill baby-sitting elders.
Other than having also written for Breitbart and other ultra-conservative media,
I know nothing about this Daniel Horowitz (not the lawyer) other than what he has written,
but I question whether he actually believes even half the stuff opined under his byline.
FWIW, credible journalism generally does not cite sources such as Gummi Bear on twitter.
While anonymous sources can be important, substantive confirmation is wanted.
Beyond that,
4 Canadian infectious disease self-proclaimed "experts" are not necessarily epidemiologists;
they may be expert at treating infections without competence at managing viral outbreaks.
It was, after all, an OPINION piece, not research.
Those Canadians did publish that
95% of COVID-19 deaths are among those over 60.
And one can even still find a few scientists with legitimate credentials
that persist in arguing against global warming; every population has a distribution...
> I like your idea, many kids including my grandson are bored at school since they learn so fast.
Along with disruptors, they should forfeit voting rights and assigned paid part-time apprenticeships,
with some sliding scale of incentives based on acquiring at least minimal literacy and math skill,
so that they have a chance to develop marketable work habits.
May 27, 2020
airborne transmission; VA case spike
Merck announced a licensing agreement with Ridgeback Biotherapeutics, a small U.S. company,
to develop a pill for treating patients already infected with coronavirus.
https://www.ft.com/content/7b72a568-9eed-460f-b100-7bf74e3f4cbf
> it is hard to know what's really going on. What do you think of
this article?
> If that is true, WHY the scare tactics with their ridiculous guidelines for opening schools?
First, that is far from what I would consider an authoritative unbiased source:
"In review, the website presents original content written by Mark Levin, and staff, as well as links to other news outlets.
Original content uses moderately loaded words that almost always favors the right."
https://mediabiasfactcheck.com/conservative-review/
During the 2012 election cycle, Levin's show was paid at least $757,000 in sponsorship
by the Koch brothers-backed Americans for Prosperity to run ads for the group
https://en.wikipedia.org/wiki/Mark_Levin
Without better treatments and/or vaccination[s],
chances of our being able to indefinitely avoid contracting the virus eventually approach zero.
Where statistically significant antibody testing has been conducted to evaluate rates of asymptomatic to verified cases,
NY had about 14% with antibodies as of Apr 23.
Those take weeks to develop; NY had about 130K reported cases around April 1,
which is about 0.67% of population, so a 20:1 ratio. Other places have estimated 6:1.
That would put our risk of dying between 0.38% and 1.3%, provided that hospitals are not overwhelmed.
On the other hand, I have not seen authoratative age breakdown for antibodies vs confirmed, but I suppose
that less than half those our age get infected without serious symptoms,
which gets us back nearer 8% risk of dying, again supposing hospitals not overwhelmed.
If school kids do pass this virus along this Fall along with significant flu
that is confused with increased COVID-19 overwhelming hospitals,
then refrigerated tractor trailers will not only be filled with dead NYC residents.
May 26, 2020
Remdesivir superior to placebo; no dark red for weekly fluctuation
Preliminary results from 1059 patients for median recovery time with 95% confidence:
11 days with Remdesivir compared to 15 days with placebo.
https://pubmed.ncbi.nlm.nih.gov/32445440/
Dark red on plots now means recent increases are over a week ago as well as previous 3 days.
This supposes that weekly fluctuations are of less concern.
May 25, 2020
restarting schools; South Korean false reinfections
So far as I know, there have been few useful antibody age demographics collected
* age distribution for antibodies
* age distribution for contact tracing
Having not closed elementary schools, Swedish antibody data are interesting:
mixed results
Colorado, Delaware, Georgia, Maine, Mississippi, Missouri,
New Hampshire, Pennsylvania, Texas, Vermont and Virginia
have all mixed antibody and diagnostic test counts;
Maine, Virginia and Vermont officials said they've fixed the issue.
New Hampshire said it reported combined numbers for only a day,
and Colorado said it did so for about a week.
https://www.cnn.com/2020/05/22/health/cdc-mixing-coronavirus-tests/index.html
Forbes looked at 25 on their list of wealthiest people
with fortunes tied to public stock, worth nearly $1.5 trillion or about 16% of total wealth held by billionaires.
They are now worth $255 billion more than on March 23.
https://www.forbes.com/sites/jonathanponciano/2020/05/22/billionaires-zuckerberg-bezos
Generated on macOS [bash script portability issues addressed]:
May 23, 2020
Cannabidiol (CBD) and coronavirus; U.S. quarantine program An enhanced gnuplot script quickly loops thru a CSV file, generating plot histories,
which fairly consistently show weekly cycles between pale and dark red new cases.
I should be able to further refine a gnuplot script to show dark red
ONLY when a county's ratio between most recent and previous 3 days' new cases
is also greater than that ratio for the previous week. This might appreciably reduce
dark red frequency, leaving any remaining more deserving of attention.
Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts
Modulate ACE2 Expression in COVID-19 Gateway Tissues
[ article by six researchers from universities of Lethbridge and Calgary, Canada
sponsored by two startup companies that do medical cannabis and disease research. ]
https://www.preprints.org/manuscript/202004.0315/v1
Although several laboratory studies indicate that both are immunosuppressant.,
CBD (unlike THC) does not appear to have any psychotropic ("high") effects
but is under preliminary research for its possible anti-anxiety and anti-psychotic effects.
https://en.wikipedia.org/wiki/Cannabidiol
A study published on Thursday in The New England Journal of Medicine explains that
COVID-19 can severely damage patients' blood vessels, causing blood to clot as it flows past.
https://www.nejm.org/doi/full/10.1056/NEJMoa2015432
Case clustering emerges as key pandemic puzzle; contact tracing; Alabama
Genetic variations potentially make some human more vulnerable,
and individuals clustered indoors talking and/or singing are most likely to be superspreader events.
https://science.sciencemag.org/content/368/6493/808
NY has put together a group of medical experts, including Michael Osterholm
from the University of Minnesota and Samir Bhatt from Imperial College London,
to monitor data and advise on pandemic management progress as the state reopens.
VA blends diagnostic and antibody test statistics
Unreliable testing data confounds understanding the pandemic's true scope.
https://www.theatlantic.com/health/archive/2020/05/covid-19-tests-combine-virginia/611620/
Per 100K calculations were moved from bash to gnuplot, improving speed and precision,
since gnuplot handles floating point and calculates columns of values per script operation.
* overall, about 5% test positive for COVID-19 antibodies
> 10-14% in and around Madrid
> 7 % of Barcelona
> 87% of those previously tested positiive by PCR test had antibodies.
> 43% of those not PCR tested but reporting lost sense of smell had COVID-19 antibodies,
compared to only 2.5% of participants who had never had any symptoms.
* This article concludes that "there is no herd immunity" in the Spanish population
https://www.vox.com/2020/5/16/21259492/covid-antibodies-spain-serology-study-coronavirus-immunity
* MY perspective: different behaviors and risk factors among and within communities;
peak infection rates naturally decline as riskier cliques acquire partial immunity.
Infections among cliques continue at reduced rates
> .. don't know why NoVA differs so much, beyond data source differences.
USAFacts links to sources, and figures match those from VA dept of health;
their data will be preferred to Johns Hopkins' henceforth.
Graphed counties were re-ordered to delay bars colliding with legends.
> Let me ask, do you think the U.S. will institute some sort of mandatory vaccination protocol
no
1) So long as KY senator is majority leader, voodoo prevails
2) Even if competent government is restored,
mandating unproven vaccine[s] is unreasonable.
Proven vaccine[s] will have been already administered to most reasonable citizens.
Some U.S. localities (NYC?) may successfully implement mandatory vaccinations.
Nearly 1 in 3 Americans planning summer road trips;
low gas prices outweigh COVID-19 fears
[ New Hampshire updates motto: Live Cheap & Die ]
https://usafacts.org/visualizations/coronavirus-covid-19-spread-map/
.. don't know why NoVA differs so much, beyond data source differences.
USAFacts 5/13 numbers match those for 5/14 froma
https://www.vdh.virginia.gov/content/uploads/sites/182/2020/03/VDH-COVID-19-PublicUseDataset-Cases.csv Albuquerque
Albuquerque is in Bernalilo County, which has 8 new cases per 100K over the last 3 days.
Two adjacent counties have higher and increasing rates
Many high case growth rate case counts are small enough to be addressed by tracing.
USAFacts data has yet to be updated for May 13, so reverting to Johns Hopkins:
These results strikingly differ from those for yesterday's USAFacts,
although spot checks among numbers from more than 2 days ago generally agree.
May 13, 2020
replacing animation by color coding
IMO, identifying locations with increasing rates of infections
is as important as comparing per capita new infections, but
implementing that by animation felt clumsy.
While switching from Johns Hopkins to USAFacts
(which data seems better, but formatted differently)
I also decided to instead color-code most recent 3-day case increases:
* pale red means latest 3-day increase is no greater than that for previous 3 days
* dark red means latest increase is greater, perhaps growing out of control:
New case rate changes can in theory be deduced by comparing red to orange,
but logarithmic distortion visually confounds that. For example,
compare relative sizes of red and orange section for NYC boroughs.
Thanks; me, too.
Graphed (per 100K) figures are ~30% higher for Cayuga
than actual new case counts, based on 76,576 population for 2019
Cayuga has averaged 3/day for the past 3 days,
compared with 1.3/day average over the previous 17 days,
based on https://usafacts.org stats, which match those from Johns Hopkins..
"successful" Infection = Exposure to Virus x Time
Anyone you spend greater than 10 minutes with face-to-face is potentially infected.
Anyone sharing space with you (say an office) for an extended period is potentially infected.
At least 44% of all infections--and a majority of community-acquired transmissions-- occur from people without symptoms.
20% of infected people are responsible for 99% of viral loads.
Biggest outbreaks are in prisons, religious ceremonies, and workplaces
such a meat packing facilities and call centers. Any environment that is enclosed,
with poor air circulation and high density of people, spells trouble.
https://www.erinbromage.com/post/the-risks-know-them-avoid-them
"Today, after 7 weeks, I feel more or less in shape for the first time." -
virologist Peter Piot
New York City excess mortality
[ comparable data for much of the rest of the U.S. may be unavailable for more than a year]
From March 11 to May 2, there were a total of 32,107 deaths,
24,172 more that the 7935 normally expected in that time based on past trends.
With 18,879 attributed to COVID-19, there were yet another 5,293 excess deaths.
Another look: animation of most recent 3 days vs previous 3
[ new cases generally increased in SC, VA & southern CA; down elsewhere ] Congrats, I guess
Finger Lakes looks to be a test case (Judas goat?) for the U.S. coming out of pandemic lock down
using "science" (or at least quantifiable criteria).
It should be "interesting" to see whether/how CNY addresses testing
https://forward.ny.gov/
https://www.governor.ny.gov/sites/governor.ny.gov/files/atoms/files/NYForwardReopeningGuide.pdf
For SC, sharp drops are not possible, since
too little testing.
> Virginia's rates were never great, and most people have had a hell of a time getting approved to get tested.
There are not enough tests to go around. NY developed their own.
> The fact that testing is dropping is NOT a good sign.
Trump's "plan" is to keep his potential voters among employees in the
dark enough to go back to work.
> So I expect an ongoing shit show for some time.
For many regions, there may not be a second wave; the first will
simply continue growing.
> As in I fully expect "virtual" school when they start this fall
> because people are going to screw up so badly, and the virus is that big a problem.
There is no real solution until vaccine and/or effective treatment and/or herd (what is left of it) immunity.
Until then, this is mostly about the rate at which vulnerable get infected.
As Fauci notes,
"The idea of having treatments available or a vaccine to facilitate
the re-entry of students into the fall term
would be something that would be a bit of a bridge too far."
While most freak about exposing kids,
numbers to date suggest they are less at risk than most others,
and weird provisions that many workers would make instead of sending
them to school,
such as baby-sitting by grandparents or unlicensed daycare, could have
worse outcomes.
Perhaps a better approach is to let kids over 12 or so remote learn,
then spread younger students among classrooms unused by teens.
> NY is advertising free testing, no symptoms necessary to qualify on the news tonight.
Great, that is presumably thanks to NY having developed their own tests.
VA has sharply reduced testing, despite major growth in northern VA cases.
Many spread the infection for a week before showing symptoms.
NY also wants a better handle on what percentage have antibodies.
Monday, VA had 989 positive results from 7562 tests, of which almost certainly most were of health workers.
bug fixes
1)
Johns Hopkins' CSV U.S. county data rows have 2 commas in Admin2 string,
confounding bash field delimiter `IFS=,`
- most recent 2 days' data went unused.
- This was unobvious in extracted case counts converted to per 100k
2) Unchanged days 3-6 were graphed red instead of orange.
Similarly for days 6-20.
https://blekenbleu.github.io/covid/
Climate advancing to deal with COVID-19 survivors
A wet-bulb temperature (TW) of 35-degrees C marks humans' upper physiological limit.
Some coastal subtropical locations have already reported a TW of 35-degrees C, and
extreme humid heat overall has more than doubled in frequency since 1979.
https://advances.sciencemag.org/content/6/19/eaaw1838
Moderna coronavirus vaccine candidate approved for phase 2 trials
Transition to phase 2 relies on immunogenic and toxicity results
from phase 1's small cohort of healthy volunteers.
Phase 2 will consist of more healthy volunteers in the vaccine target population
(~hundreds of people) to determine reactions in a more diverse set of humans and test different schedules.
more of the same
"There's a metric that can indicate when it is safe to reopen society
that does not depend on politics or guesswork. It's called excess mortality."
Fails to mention:
1) U.S. weekly death rates by county are NOT well maintained
2) weeks of delays between public health measures and death rate impacts
3) partitioning by age group
https://www.washingtonpost.com/opinions/2020/05/04/metric-that-could-tell-us-when-its-safe-reemerge
Kids' role in COVID-19 pandemic
Denmark sent children up to age 11 back on 15 April,
and Germany welcomed back mostly older children on 29 April.
Some Israeli schools reopened on 3 May;
Netherlands and Quebec plan to reopen many primary schools on 11 May.
https://www.sciencemag.org/news/2020/05/should-schools-reopen-kids-role-pandemic-still-mystery
GitHub scripts have portability fixes and handle more cumulative case counts
that are decreasing in reports. https://blekenbleu.github.io/covid/ flipped
Log scale visually exaggerates smaller numbers,
but most recent case increases are more important,
and flipping plot order makes more obvious, e.g.
that new case rates in parts of VA are comparable to metro NY's:
May 06, 2020
Swedish kids are OK
Swedish preschools and elementary schools have remained open,
in part to avoid healthcare workers staying home with their children.
Secondary schools and universities are closed.
https://en.wikipedia.org/wiki/COVID-19_pandemic_in_Sweden
Steady increases reported mostly everywhere except SC:
https://blekenbleu.github.io/covid/
> We will not be transporting every kid to school 180 days a year for some time,
> and that is a good thing.
Given how few parents are capable of instilling learning skills, I suppose that
institutionalized elementary school will continue being essential,
and Swedish experience suggests that it is not particularly risky for COVID-19.
> That last chart is really helpful in showing the increase
> and if you could move the lines around,
> you could see who is doing well vs who is not doing so well
Not sure what you have in mind;
they are currently sequenced to suggest what is happening in county clusters.
Here is
a re-ordering by reported cases in most recent 20 days.
It is hard for me to locate e.g. Beaufort, SC, while also concerned about Jasper
(less than a mile away) and Chatham, GA (Savannah daily commuters).
I have considered putting red leftmost, then orange, yellow, gray
to magnify recent case growths, given log scale..
May 05, 2020
Re: children and COVID-19 [again]; trends
Kids' role in pandemic still a mystery [AKA "known unknowns"]
With NY metro stuck around 1% confirmed case over most recent 20 days,
perhaps corresponding to 5% including untested,
NYC might have 100% herd immunity, if such actually exists, within a year.
While red vs orange in this bar chart is intended to indicate recent trends,
an animated GIF shows trending since March 25, for those interested.
At nearly 400KB, it is posted on the web, rather than as an email attachment:
https://blekenbleu.github.io/covid/
Today's update:
Meanwhile:
Comparing to yesterday's graph, some places with relatively small (or no)
orange may report mostly in multi-day batches. Graphing weekly data
would smooth such results but delay showing serious increases,
such nearly doubling over 3 days in Colleton, SC Bastrop, TX and Rappahannock, VA
(keeping in mind logarithmic scaling, which visually deemphasizes counts from more than 20 days ago).
This design intentionally portrays relative contagion risks;
while e.g. Westchester NY has nearly twice as many recovered as currently contagious,
that is not enough immunity to appreciably reduce infection rates. Contact tracing, explained
Essential work for safe reopening https://www.vox.com/2020/5/4/21242825/coronavirus-covid-19-contact-tracing-jobs-apps
Some U.S. localities have relatively current data:
"NY Times" may have cherry-picked these as click-bait or to encourage social isolation.
Despite U.S. influenza + pneumonia + COVID-19 deaths up:
... some states may be experiencing reduced all-cause mortality, thanks to the
Peltzman effect https://en.wikipedia.org/wiki/Risk_compensation#Peltzman_effect
... and those governors could arguably justify partial reopenings,
given credible current all-cause death rates.
Today's chart introduces orange, for previous 3 days, while red is still most recent 3.
Since scale is logarithmic,
an equal increase for previous will plot somewhat thicker than for new.
Clearly, some Texas counties are reporting significantly greater increases.
Nearly all current cases for e.g. Seneca NY have been reported within these 6 days.
Rappahannock, VA is also reporting an urgent situation
With 1.8% average testing focused on critical workers and obviously sick,
generalizing (~1/6 positive) results:
https://public.tableau.com/views/COVID19inUSA/COVID-19spreadinUSA
... has dubious validity. On the other hand there may be some
most likely ratio of those sick enough to get tested vs. actual infections,
which coincidentally also may be ~1/6.
3) extended script with bug fix:
* Yesterday, 'current' wrongly included most recent 3 days, so double-counted.
* Updated bash script now downloads
most recent csv
extracts county stats, gnuplots and rotates in about 8 seconds.
* counties better rearranged to cluster by locality
* two KY counties (Woodford & Scott) now report decreasing cumulative values..??!!
May 01, 2020
ribonucleoside analog NHC (B-D-N4-hydroxycytidine)
Taken orally soon after infection, this drug is incorporated into the viral RNA,
inducing "lethal mutagenesis" (the virus fails to propagate).
NHC appears to be potent against many coronaviruses,
It could also potentially be used as a prophylactic..
The paper has yet to undergo peer-review;
as yet undiscovered flaws may undercut findings.
The medicine, AKA "EIDD-2801", has yet to be tested on humans.
The FDA has granted permission for patient trials within a few months. https://indyweek.com/news/northcarolina/unc-researchers-covid-19-EIDD-2801/
Studying R motivated rethinking what and how to display results
still using bash and gnuplot scripts:
bars clustered by location, rather than sorted by value
for example, without metro region, NY state seems better than VA
plot values per 100K population, so larger than actuals for sparse counties
values are reported/confirmed
multiplying e.g. NYC ~3% by 6 approximates actuals
scale is logarithmic
NY metro region values are so much larger than others
width of red (new cases) reflects growth rate for any population
Bamberg SC has highest growth rate
Despite supposed cumulative values, some county updates are decreased values...??!
Apr 30, 2020
new cases for selected counties
While studying R,
I discovered a better COVID-19 data source, so this plot shows
% increase over the most recent 3 days and approximate active cases,
based on confirmed cases for most recent 20 days.
That should probably be multiplied by 6-7 for estimating actual infections.
One hopes that Seneca NY, Barren KY and Rappahannock VA recently increased testing.
I let gnuplot clip 10 most active cases...
.. for which here are data:
testing and delays
NY Gov. Cuomo identified 70% hospital capacity as a threshold for shelter in place;
this article identifies tracing capacity as a key constraint for keeping it below 70%. https://medium.com/@tomaspueyo/coronavirus-how-to-do-testing-and-contact-tracing-bde85b64072e
It is a long read; to summarize:
without an app based on Google/Apple smartphone tracing,
this pandemic continues until immunity, which requires either:
* vaccine[s], or
* a majority having contracted it and, lacking effective treatments:
- deaths of most vulnerable 1-2 million U.S. residents, which is
~ 2/3 of annual deaths from all causes.
- FWIW, flu typically causes 2% of all deaths https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_09-508.pdf
> If you are to summarize all of your research
> do you think this boils down to a much worse second wave?
I watch daily briefings by NY Gov Cuomo, who points out
that depends on how folks behave. Just as with the first wave,
localities will experience it at different times and strengths.
I >>SUSPECT<< that, in much of the country,
even if/when states implement tracing,
many of those contacted and directed to isolate will NOT.
Meanwhile, if Trump prevails in forcing meat packers to reopen,
a second wave in those communities will overwhelm their health systems
and undertakers. On the other hand, they will develop herd immunities...
I expect a second wave here, starting around May 15,
as vacationers pile into Hilton Head.
With summer tourists continually arriving and leaving,
appreciable herd immunity may not evolve.
Since it is to me unclear whether/how much infection was spread in schools,
I expect a second wave in some states to not wait for Fall
and be indistinguishable from a prolonged first wave.
My model suggests that 20% herd immunity may dampen a second wave,
provided that infected populations are sufficiently depleted,
which requires about 3 weeks of very few new cases.
Refining my model wants more data and better visualizations;
I am studying R and specifically tidyverse:
https://r4ds.had.co.nz/introduction.html#prerequisites
I suspect that Gov. Cuomo's 70% hospital occupancy threshold
will prove to be sadly optimistic, given approx 10 day delays
between infections and hospitalizations. On the other hand,
he may fear losing control by holding out for safer thresholds.
Apr 28, 2020
Map of last 4 week COVID-19 case density increase by U.S. county
Toward the bottom at this URL is an interactive map
for most recent 4 weeks cases per thousand residents: https://www.nytimes.com/interactive/2020/04/03/upshot/coronavirus-metro-area-tracker.html
IMO, most recent 1 week would be more useful than 4 weeks.. Per-capita increases:
.08% for Bluffton, SC; .06% for Auburn, NY, .04% for Lexington, KY;
.13% for Louisville; .08% for San Francisco; .07% for San Diego, .14% for NYC
.13% & .43% for Boulder & Greeley CO; .02% for Longview, WA;
.08% for Austin, TX; .18% & .05% for St Louis & Jefferson City, MO
For example, 11% confirmed cases in Weld, CO implies significant herd immunity developing,
which my model suggests could begin slowing growth within a month.
Weld has intensive testing; actual/confirmed is probably lower there than elsewhere.
At 0.2%, Kershaw has highest cumulative cases in SC;
6.5:1 actual to confirmed yields only 1.3%, a long way from reducing growth.
NYC reports 3.5% confirmed; antibody survey reported 21% (so 6:1);
partial herd immunity may be helping.
Another CSV (comma separated variable)
data source for mapping daily county cases: SC: 5613 known => 38,896 estimated cases?
[ How can an estimate have more digits of precision than a known? ] https://www.postandcourier.com/health/covid19/
135/100k known cases in our (Beaufort) county maps to 0.9% estimate...
not enough herd immunity to appreciably reduce infection rate.
Apr 27, 2020
Re: U.S. cases by county (FIPS code) - work still in progress
An updated script works better, and data is updated to Apr 26/19
I still intend to look into color-coding a FIPS county map,
but first reduced the report to counties of interest,
e.g. those which addressees are in or near.
I selected 88 counties; let me know if you want others.
This plot is sorted by percentage increase (purple) and also
plots increased cases per 100K population (cyan) from April 19 - 26
Several VA, CO and upstate NY counties seem problematic.. Map of cumulative COVID-19 Case Density by U.S. County
maps of current cases/100K and case growth % are more interesting,
but it's a start: https://covid.yale.edu/innovation/mapping/case-maps/population-density/
...using Bash e.g. in macOS, Linux or Ruby
2700 is far too many counties for practical gnuplot; here are highest percentage growth 100:
Apr 25, 2020
Dr. David Katz | Real Time with Bill Maher
Two issues not addressed:
(1) wearing masks to (2) avoid overwhelming hospitals https://www.youtube.com/watch?v=Lze-rMYLf2E 4.5% case growth; Hospital Referral Regions (#HRRs)
New case growth rate is basically a proxy for risk of infection.
Mark Handley is another non-medical techie crunching statistics: http://nrg.cs.ucl.ac.uk/mjh/covid19/#covid-us-norm
Note that graph is NOT new cases, and Mark shifted plots to match 4.5% tangents.
It sort of suggests that it takes 20-30 days for recoveries to start
reducing case growth,
then 10 days or so for increasing partial herd immunity to begin
reducing new case rate.
Partial herd immunity may kick in so promptly because of
self-selection among most risky.
Mark's next chart shows NEW case growth rate differences,
presumably consequences of risk circumstances and behaviors
(public transportation, urban/rural, local edicts): http://nrg.cs.ucl.ac.uk/mjh/covid19/#rates-us
Growth rate by state is less useful for folks e.g. in upstate NY
or even here, since reports vary by over 4:1 within SC,
and Bluffton is more a holiday destination and Savannah GA suburb
than related to Charleston, much less Columbia, Greenville, Florence
or Spartenburg.
old-fashion (chemically inactivated virus) vaccine effective in monkeys
PiCoVacc confers complete protection in non-human primates
eliciting potent humoral responses devoid of immunopathology https://www.biorxiv.org/content/10.1101/2020.04.17.046375v1
"I like it," says Florian Krammer, a virologist at the Icahn School
of Medicine at Mount Sinai who has co-authored status report
about many different COVID-19 vaccines in development. https://www.cell.com/immunity/pdf/S1074-7613(20)30120-5.pdf
"This is old school but it might work.
What I like most is that many vaccine producers,
also in lower-middle-income countries, could make such a vaccine." Masks work
50% of infections are from persons not showing symptoms;
contagious for less than 2 weeks (?)
Vacuum cleaner bags are nearly as good as surgical masks.
60% of people wearing masks that are 60% effective might, by itself, stop the epidemic.
Apr 23, 2020
Cuomo: over 20% of NYC population tests positive
[12:05/55:25] https://www.youtube.com/watch?v=IIru8C-ayYk
My primitive model suggests that, if NYC can get their hospitalization rate down,
then (supposing acquired immunity) NYC's 20% reduction in susceptibility
(AKA partial herd immunity) may make reopening there not much more risky than upstate,
where contagion risk is lower, but over 96% remain susceptible.
To avoid excess mortality, 'not much more risky' still IMO wants
masks on everyone in public along with distancing, massive testing and tracing. asthma sufferers strikingly underrepresented among COVID-19 deaths
[ instead, blood clotting ]
Nearly 8% of U.S. population has asthma. When the novel coronavirus first hit,
the Centers for Disease Control and Prevention and others put people
with asthma at the top of their lists of those who might be the most vulnerable.
But European researchers writing in the journal Lancet noted
it was striking how underrepresented asthma patients had been.
Earlier this month, when New York state released data about
the top chronic health problems of those who died of COVID-19,
asthma was not among them.
Instead, they were almost all cardiovascular conditions.
r[0] supposes that, given a population with no resistance at time t=0,
there is a meaningful ratio for how many others will catch an infection from any spreader.
The SIR model postulates that, at any time,
the rate of new infections is product of susceptible population s(t) times infected population i(t) times time-dependent factor r(t).
Further, recovery rate d(r)/dt is some constant rate times the infected population
https://en.wikipedia.org/wiki/Mathematical_modelling_of_infectious_disease#The_SIR_model
It is, IMO, silly to suppose that:
* someone who just caught a disease is equally likely to "recover" at any time, and
* infection rate for a given virus should appreciably change over time.
Seemingly more credible:
* some average period of time that folks are contagious, and
* some probability that contagion occurs.
Here are gnuplots based on my assumptions of:
* 20 days average contagion, and
* 1.5% or 2.5% probability of contagion during that period,
* starting with a single carrier:
Behavior drives contagion risk, as may perhaps weather/season..
Something approximating "herd immunity" obtains
after about double the peak interval. Of course, if risky behavior increases,
subsequent peaks are possible, with correspondingly higher herd immunity rates.
This all supposes that non-trivial immunity actually occurs...
While that roughly 20% peak contagious population seems scary,
20% may not be all that far off what is happening with asymptomatic COVID-19...
Here is (fairly readable) gnuplot source.
SC model
Rather than merely speculate, I hacked the gnuplot SRC model
to approximate South Carolina statistics according to Washington Post:
...and predicted politics according to me.
In the next graph, C represents the model's contagious population percentage, R represents recovered (no longer susceptible) and S represents remaining susceptible.
Day 30 on the model graph corresponds to April 9, which was the peak day (so far)
on the Washington Post graph. The model switches from 1% to 2% contagion
on day 41 (April 20), corresponding to SC governor reopening many businesses,
noted reduction in mask wearing and increased traffic.
* After a 7 day delay for new cases to get serious, publish cases spike.
In real life, spikes will spread with some getting sicker sooner or later..
* Supposing resumed stay at home around April 30, that spike should relent,
delayed by another week or so.
The same model is plotted here for 300 days:
Supposing the governor again reopens business around May 15,
another, lower, spike provokes no reclosing. By this time,
the population percentage still susceptible will have been reduced so that
resumption of more riskier behavior may not overtax the healthcare system...
Apr 20, 2020
Re: COVID-19 Rt, "the effective reproduction number" Here is a blog post discussing their approach to estimating Rt.
My specific interest was how they estimate contagious populations,
for which they reportedly use previous 7 days' positive tests.
Since folks may be contagious for longer, this should overstate Rt.
However, since positive test results understate actual infections,
I consider their 7 day approximation as a fudge factor that was tuned
to match their model to reported data. Consequently, one could
expect different fudge factors to better fit different populations at different times,
depending on [mis]behaviors.
Again, since their Rt proxy is effectively based on hospitalizations,
it lags real active Rt by over a week.
Since we have already seen positive test reported values double in under 2 days,
a locality wants their rate before relaxing mitigations to be
less than 10% of whatever is considered a tolerable rate,
which might arguably be based on excess mortality..
About half way down this blog post, Mr. Systrom ranks rates per state
by median, then worst-case estimated values.
This latter clusters states with fewest tests and least mitigations.
On the other hand, while that makes LA appear to be in relatively good shape,
I fear that it instead reflects recent testing biased towards folks with influence
more that folks with symptoms. Indeed, Louisiana's death rate remains relatively high:
https://www.nytimes.com/interactive/2020/03/21/upshot/coronavirus-deaths-by-country.html
... with many deceased untested and thus excluded.
Apr 19, 2020
COVID-19 Rt, positivity rate
Rt: virus growth
color-coded for trending per state https://rt.live/
Positivity Rate
According to Tracking Project figures,
nearly 20% of people in the U.S. tested have been positive for the coronavirus,
but actual prevalence in general population is presumably lower, thanks to
testing largely limited to those symptomatic and/or known to have been exposed.
If the outbreak were indeed under control,
then more testing should yield a smaller proportion of positives.
So far, that hasn't happened.
Virtually the only wealthy country with a larger positivity rate than the U.S. is the U.K.,
where more than 30% of tests have been positive.
This chart does NOT plot changes in % positive with increased testing,
merely percentages of tests that have been positive.
The horizontal scale goes from 0.6 to just over 3%
Results in states below 1% are presumably overweight for healthcare workers.
Here are CHANGES in positive test percentages:
Horizontal scale is 0.13% to 0.82%
Label oops: AZ should be over with MO
States with increasing infection test rates should be prepared for increasingly bad news.
I expect this will provoke panic-buying e.g. of chicken, etc.
Meanwhile, a predicted heavy hurricane system will provoke mass evacuations
in a time of "social distancing"
excess mortality
I wrote an email to our U.S. Congressman, suggesting that a total death rate should be tracked
in comparison to that seasonal per capita rate e.g. averaged over the previous 5 years.
This might address the problem of population testing insufficient for statistical significance,
with residents dying without having been tested
and sick folks electing to forgo hospitals and testing, given a lack of effective treatments.
So-called social distance in the U.S. was substantially motivated by this:
Note that excess mortality is plotted there, based on hindsight,
lacking explicit verification for Spanish flu. https://en.wikipedia.org/wiki/Spanish_flu
The present mobility reduction has presumably also reduced flu infections and deaths.
In some localities, e.g. where influenza rarely spreads, overall death rates may be
lower than normal because of reduced motor vehicle usage and accidents.
In a few places, deaths may have increased either by random bad luck
or risky behavior such as driving faster because of less traffic on dangerous roads
leading to disproportionally more fatal accidents.
If there are localities that report decreased total mortality rates,
mobility restrictions arguably somehow could be loosened,
although that could provoke migration from places with more restrictions and disease.
About half-way down that same page are new cases for some metro areas,
not including e.g. Savannah GA (about 30 minutes from our home).
FWIW, Syracuse NY looks hopeful., particularly compared to e.g.
Buffalo, Atlanta GA or Columbia SC.
German germs
While the Institute of Virology at Bonn University detected COVID-19 RNA
on surfaces in a household where many highly infectious people lived,
they were unable to cultivate the virus in a laboratory from those swabs.
Serology testing 500 residents of hard-hit Gangelt showed that
14% have antibodies,
which is roughly 6 times their reported COVID-19 rate.
Andriod & iOS contact tracing apps by mid-May: "viral malware"
> On the weird side, St Joe's hospital in Syracuse layed off workers
> because no one is having elective surgery and there is not enough hospitaliztions of Corona to keep them busy...
> Rochester is eeriely quiet (not sure if it is Strong or U of R)..
KY Hospitals similarly laid off many employees unrelated to COVID-19 care.
SC case growth is not expected to peak before the end of April
> Cayuga County NY has had 561 tested, 537 results, 31 positive for 6%
Wow, testing here is about 50% positive.
Apr 11, 2020
> I listen to Gov Cuomo every day,
> and he has said for a few weeks that the death numbers will peak a week to 10 days after the peak of the hospitalizations.
I have not found data for hospitalizations vs positive cases reported;
my current best guess for NY is 13 day average delay from reported to deaths.
3.5 weeks ago, it appears to have been around 7 days delay,
then 10 days from 2 to 3 weeks ago
and 12 days delay 1 week ago.
Today, Cuomo reported that hospitalizations are down.
I only access data for the state, which continues reporting relatively
constant 10K new cases per day,
so hospitalizations may be down in NYC metro area but up elsewhere...?
active growth update
NY having increased only 10% over 4 days may seem encouraging,
but would still result in doubling over a month.
I wonder whether CT will be in the news before its hospitals overflow?
There seem to be far too many yahoos who suppose physical distancing
can reasonably be relaxed before folks are vaccinated.
more gnuplots
A professional perspective on COVID-19 statistics
To visualize whether/when cresting occurs in selected states,
my first chart plots growth in positive tests between April 5 and 7.
AZ is behaving, CT is doomed and GA will pay for their governor's foolishness.
Since any sick folks that we personally know are not included,
a second chart plots percentage testing growth vs percentage of population,
keeping in mind that many tests are duplicates for critical workers.
COVID data from states with tests < 1% of population are IMO suspect.
NC is flying blind. CA is waiting for results from nearly half its tests.
Only 4 states report positive COVID for more than 1/1000: NY, NJ, MI, WA.
Other states may have less COVID or insufficient testing.
MI is interesting; after bad-mouthing its governor,
someone presumably pointed out to Trump that he would need their votes.
Since https://covidtracking.com reports cumulative totals,
a third plot subtracts Mar 22 totals from April 7 totals,
(supposing most reported cases remain active for about another 2 weeks)
and compares that difference to Mar 29 total. Except for WA, that reduces totals by < 10%.
While not all active cases are hospitalized,
scaling to better approximate states' healthcare stress now uses
available beds (from https://covid19.healthdata.org) rather than population.
CT and NJ should soon be getting as much attention as NJ.
For the 4 states with most active cases per hospital bed,
their rates of reported case increases over the last week
are negatively correlated to their active case loads,
which could mean that distancing is beginning to work for them
or they are too stressed to fully report.
Apr 6, 2020
COVID growth stress
Positive tests updated to Apr 5
and X axis changed to percentage of state population,
which is probably a better approximation of stress on states' healthcare resources:
hospital beds
state crest wanted/available
NY Apr 8 196%
NJ Apr 15 316%
MI Apr 8 85%
GA Apr 20 82%
FL Apr 21 65%
IL Apr 16 64%
VA Apr 20 43%
KY Apr 21 42%
WA Apr 2 20%
NC Apr 13 19%
CA Apr 14 18%
MO Apr 19 17%
SC Apr 24 15%
AZ Apr 23 14%
TX Apr 19 13%
PA Apr 12 12%
Other states with projected bed shortages: RI, NV, MA , MD, CT, AK
NY is projected to still need over 3K ventilators by Apr 18;
unlikely to have released many to other states.
Available hospital beds are NOT proportional to population;
I'll be updating my chart...
Apr 5, 2020
COVID-19 positive test growth
States want to avoid being in the upper right quadrant.
PA and NJ seem vulnerable, then FL and MI.
Washington state is doing relatively well by less than doubling.
This supposes that state data are comparable,
despite e.g. NY having tested over 3x more of its population than others.
# increased Mar 22 Mar 29 Apr 4 COVID population
# residence COVID COVID COVID tests K K
10 152 919 2019 27.1 7279 # AZ
15 1536 5708 12026 113.7 39512 # CA
13 830 4246 11545 105.9 21478 # FL
11 600 2651 6383 26.5 10617 # GA
13 1049 4596 10357 53.6 12672 # IL
9 99 394 917 16.7 4468 # KY
12 1035 5486 14225 26.1 9986 # MI
9 90 838 2291 27.2 6137 # MO
16 1914 13386 34124 75.4 8882 # NJ
16 15168 59513 113704 283.6 19454 # NY
10 255 1040 2402 38.8 10488 # NC
10 351 1653 3739 41.9 11689 # OH
12 479 3394 10017 70 12802 # PA
9 195 774 1917 18.3 5149 # SC
13 334 2552 6110 63.8 28996 # TX
11 219 890 2407 21.6 8536 # VA
13 1793 4310 7591 87.9 7615 # WA
3-29/2-16 Mar 22 Apr 4 positive 2020 tests reported
state residence positive positive increase census reported ratio
CA +15% 1536 10701 697% 37255k 35.3k .09% 59.5k pending
FL +13% 830 10268 1238% 21478k 94.4k .44% 1.4k pending
GA +11% 600 5967 995% 9688k 25.4k .26%
KY +9% 99 831 839% 4339k 15.6k .36%
MO +9% 90 2113 2348% 5989k 26.8k .45%
NY +16% 15168 102863 678% 19378k 271k 1.4%
SC +9% 195 1700 872% 4625k 16.2k .35%
TX +13% 334 5330 1596% 25146k 55.8k .22%
VA +11% 219 2012 919% 8001k 19k .24%
It is encouraging that 2 highest increased residence rates have lowest CIVID growth rates.
Missouri is worrying, but perhaps reflects better test reporting now than earlier.
This also does not capture how risky is typical behavior away from home...
> Why case counts are meaningless without information about testing coverage:
> https://fivethirtyeight.com/features/coronavirus-case-counts-are-meaningless/
> e.g. why West Virginia was the last state to get a case...
I should have also tabulated states' percentage of population tested,
but even then would not know how much bias/credibility for
establishing error bars...
As time goes on, many of the same critical workers may be retested,
which is not being delineated.
Apr 3, 2020
DIY masks using HEPA vacuum cleaner bags
I ordered upright vacuum HEPA bags from eBay for this pattern
Most HEPA vacuum bags are made with fiberglass,
which can be an irritant.
Enclosing them in cotton cloth envelopes addresses that.
Mar 31, 2020
Re: Washington Post dynamic graphical simulation of disease spread
> An interesting computer simulation addressing social distancing.
> https://www.washingtonpost.com/graphics/2020/world/corona-simulator/ Excellent!
> I hope people will pay attention and actually start doing their part.
Sadly, that's NOT happening here in Sun City;
oldsters vehicular traffic is about as heavy as before SC disaster
declaration.
Significant influx of Ohio, New Jersey, etc relatives around the neighborhood.
.01% KY (same as Texas) vs .02% SC, .017% VA positive.
13 have died from COVID-19 in SC since Mar 22.
If 1% die, then SC may have had 1300 cases a month ago.
SC reports 774 cases today, compared with 195 a week ago.
Given 4x growth per week, SC may now have about 200,000 cases.
Mar 29, 2020
SC COVID-19 severity by age
South Carolina received a federal disaster declaration for COVID-19 on Mar 28.
With a population of over 5.2 million, South Carolina reports testing 3,675 or 0.07%,
with 18% positive and most negative tests presumably among health workers.
Given general population testing effectively limited to those with serious symptoms,
this may be a good population for estimating how serious are symptoms among
and between age groups. For example, the percentage of positive tests
among those 40-50 is roughly the same as their percentage of SC population.
Folks 60-70 appear 73% more likely than them to have severe symptoms
while children 10-20 are only 30% as likely.
/media/img/posts/2021/02/8_US_Cross_Curves1/original.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22032257/third_wave_hosp_covid_chart_nov11.jpg)
/media/img/posts/2020/11/nayQLspw/original.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/21867227/coronavirus_deaths_developed_nations_chart.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/21867117/coronavirus_cases_states_map.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/21867141/coronavirus_rt_states_map.png)
/cdn.vox-cdn.com/uploads/chorus_asset/file/21786134/US_vs_NZ_Covid_19_cases.gif)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/21729870/coronavirus_epidemics_states_map.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/20883404/coronavirus_epidemics_map.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/20919630/full_list_covid_19_tests_per_day.png)
:format(webp):no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/20537786/Screen_Shot_2020_07_28_at_10.38.36_AM.png)
