SARS-CoV-2 and COVID-19 (18)

Coronavirus digest: German nursing home sees (B117) outbreak after (Pfizer) vaccines
DW (2/9/2021?)

Fourteen residents at a German nursing home have tested positive despite receiving... two doses of the (BioNTech-Pfizer vaccine, with their last shot on January 25)

Local officials in the district of Osnabruck, Germany, said there was an outbreak of the UK variant of coronavirus at a nursing home in Belm.

...14 residents tested positive for the virus at the end of last week (week ended Feb 6).

None of them showed any serious symptoms associated with COVID-19. It is unclear exactly how and when the residents became infected...

https://www.dw.com/en/coronavirus-digest-german-nursing-home-sees-outbreak-after...

Uh oh. Hopefully it won't be as severe as it would have been without the vaccine.

Yeah, fingers crossed: still early in course of disease. Maybe, elderly people need more time to fully develop immunity? (Let's hope.)
Sounds like we'll be dealing with this *&(%^$$#@ virus for foreseeable future... :(
Not yet time to relax our guard--or for scientists to plan summer vacays...

Eric Feigl-Ding (epidemiologist, economist) @DrEricDing | 6:10 PM · Feb 8, 2021:
https://twitter.com/DrEricDing/status/1358916234650275848

OUTBREAK OF #B1351 (first reported in South Africa) VARIANT IN AUSTRIA
—B1351 variant now identified in 293 cases in western Austria state of Tyrol—at least 140 active cases. Germany is considering closing the border to Tyrol. Austria govt has issued urgent travel warning. #COVID19

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For those of you who read (German?):

Blick auf die Triumphpforte in Innsbruck, dahinter die Nordkette. | dpa
Südafrikanische Corona-Mutante Österreich warnt vor Reisen nach Tirol

Stand: 08.02.2021 18:42 Uhr

Die südafrikanische Corona-Variante breitet sich in Tirol stark aus. Deswegen stand sogar eine Abriegelung des österreichischen Bundeslandes im Raum. Vorerst sieht die Regierung in Wien davon ab - warnt aber vor nicht notwendigen Reisen....

https://www.tagesschau.de/ausland/europa/tirol-reisewarnung-corona-101.html

CDC: intent to receive COVID-19 vaccination.

Nguyen KH, Srivastav A, Razzaghi H, et al. COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among Groups Prioritized for Early Vaccination — United States, September and December 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 February 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7006e3 https://www.cdc.gov/mmwr/volumes/70/wr/mm7006e3.htm

Summary

What is already known about this topic?
National polls conducted before vaccine distribution began suggested that many persons were hesitant to receive COVID-19 vaccination.

What is added by this report?
From September to December 2020, intent to receive COVID-19 vaccination increased from 39.4% to 49.1% among adults and across all priority groups, and nonintent decreased from 38.1% to 32.1%. Despite decreases in nonintent from September to December, younger adults, women, non-Hispanic Black adults, adults living in nonmetropolitan areas, and adults with less education and income, and without health insurance continue to have the highest estimates of nonintent to receive COVID-19 vaccination.

What are the implications for public health practice?
Ensuring high and equitable vaccination coverage among all populations, including by addressing reasons for not intending to receive vaccination, is critical to prevent the spread of COVID-19 and bring an end to the pandemic...

Eric Feigl-Ding @DrEricDing | 3:40 PM · Feb 8, 2021:
Immunocompromised 45 year old suffered from #COVID19 for 155 days before he died.
The virus was changing very quickly inside the man's body—it acquired a big cluster of more than 20 mutations—
resembled the same ones seen in #B117 (UK) & #B1351 (S Africa).
2:10, 1:11 ( NPR, https://twitter.com/DrEricDing/status/1358878419438751744 )

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Extraordinary Patient Offers Surprising Clues To Origins Of Coronavirus Variants
Michaeleen Doucleff | February 5, 2021
Heard on All Things Considered: 4:16 ( https://www.npr.org/programs/all-things-considered/2021/02/05/964384198 )

https://npr.org/sections/goatsandsoda/2021/02/05/964447070/where-did-the-coronav...

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Bina Choi et al. 2021. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. NEJM December 3, 2020
N Engl J Med 2020; 383:2291-2293 DOI: 10.1056/NEJMc2031364 https://www.nejm.org/doi/full/10.1056/NEJMc2031364

...Phylogenetic analysis was consistent with persistent infection and accelerated viral evolution... Amino acid changes were predominantly in the spike gene and the receptor-binding domain, which make up 13% and 2% of the viral genome, respectively, but harbored 57% and 38% of the observed changes...

...Although most immunocompromised persons effectively clear SARS-CoV-2 infection, this case highlights the potential for persistent infection and accelerated viral evolution associated with an immunocompromised state....

Plain language overview.

What to Know About B.1.1.7, the Coronavirus Variant That Could Soon Dominate the U.S.
It was first detected in Colorado in December—and has already spread to more than 30 states.
Korin Miller | Feb 9, 2021
https://www.prevention.com/health/a35120192/what-is-b117-variant-covid-19-corona...

Rapid coronavirus tests: a guide for the perplexed
Scientists still debate whether millions of cheap, fast diagnostic kits will help control the pandemic. Here’s why.
Giorgia Guglielmi (Nature NEWS FEATURE) | 09 February 2021

As the number of UK coronavirus cases surged in early 2021, the government announced a potential game-changer in the fight against COVID-19: millions of cheap, rapid virus tests. On 10 January, it said it would roll these tests out across the country, to be taken by people even if they have no symptoms. Similar tests will play a crucial part in US President Joe Biden’s plans to tame the raging outbreak in the United States.

These speedy tests, which typically mix nasal or throat swabs with liquid on a paper strip to return results within half an hour, are thought of as tests of infectiousness, not of infection. They can detect only high viral loads, so they will miss many people with lower levels of the SARS-CoV-2 virus. But the hope is that they will help to curb the pandemic by quickly identifying the most contagious people, who might otherwise unknowingly pass on the virus.

...How Covid-19 Tests Work (Infographic)...

...Catching Covid (Infographic)...

...Rapid Tests Detect high Virus Loads (Infographic)...

...Rapid Tests: Suitable at Home? (Infographic)...

https://www.nature.com/articles/d41586-021-00332-4

Could a Single Vaccine Work Against All Coronaviruses?
Carl Zimmer | Feb. 9, 2021

Scientists are working on a shot that could protect against Covid-19, its variants, certain seasonal colds — and the next coronavirus pandemic.

...researchers are starting to develop prototypes of a so-called pancoronavirus vaccine, with some promising, if early, results from experiments on animals. Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in San Diego, thinks scientists should join together in another large-scale vaccine-creation project immediately.

“We have to get a real work force to accelerate this, so we can have it this year,” he said. Dr. Topol and Dennis Burton, a Scripps immunologist, called for this project on broad coronavirus vaccines on Monday in the journal Nature* ...

https://www.nytimes.com/2021/02/09/health/universal-coronavirus-vaccine.html

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Variant-proof vaccines — invest now for the next pandemic
COVID’s evolution signals the importance of rational vaccine design based on broadly neutralizing antibodies.
(NATURE) COMMENT
Dennis R. Burton & Eric J. Topol | 08 February 2021

...In evolutionary terms, SARS-CoV-2 is an ‘evasion-light’ pathogen. It has not had to acquire an armamentarium of molecular features to outwit immune responses in general and neutralizing antibodies in particular. This is because it currently transmits from one person to another before immune responses have developed — and, in many cases, before disease symptoms are noted.

Other pathogens are ‘evasion-strong’. The extreme example is HIV. It frequently co-exists with human immune systems, possibly for years, before onward transmission. So it has developed many ways to stymie our defences, including extensive sequence variation. This is known as immune escape. Even in one infected person, there can be 100,000 different HIV strains, any of which could be transmitted.

...Influenza virus is another evasion-strong pathogen. Its huge sequence variability is a challenge for vaccine design.

...Several notable variants of SARS-CoV-2 have emerged in recent months, including B.1.1.7, B1.351 (also known as 501Y.V2) and P.1. These were first identified in the United Kingdom, South Africa and Brazil, respectively, and each variant has many mutations in the crucial spike protein. Laboratory studies suggest the potential for immune escape... with at least one of these variants.

...Crucially, early containment or eradication of an emerging virus would greatly reduce the likelihood of it evolving resistance to antibodies and vaccines.

Cost and investors
Unlike a reactive programme that swings into action when a new pathogen appears, our proposal has goals that can be described now and projects that could begin on a large scale immediately. Thanks to work already done on other viruses, particularly HIV and influenza, the approaches are understood and the infrastructure is in place. Investments made so far in basic science — including virology, genomics, immunology and structural biology — have afforded us a remarkable opportunity to get ahead of further SARS-CoV-2 evolution and put us in a powerful position of readiness for new viral pathogens.

The investment per virus from bench to phase I trials is likely to be in the range of $100 million to $200 million over several years. We envisage that these costs would be borne by public–private partnerships between governments, philanthropy and industry. Organizations such as CEPI, the COVAX Facility and GAVI, the Vaccine Alliance could help to convene the expertise and initiate the negotiations needed to deliver the types of vaccine we propose.

We will have outbreaks in the future, and are very likely to see further epidemics. We must stop these becoming pandemics.

doi: https://doi.org/10.1038/d41586-021-00340-4
https://www.nature.com/articles/d41586-021-00340-4

UK preprint: "inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation"

Sanjay Ramakrishnan et al. 2021. Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial. MedRxiv (Feb 8, 2021) doi: https://doi.org/10.1101/2021.02.04.21251134 https://www.medrxiv.org/content/10.1101/2021.02.04.21251134v1

This article is a preprint and has not been certified by peer review

Abstract
Background
Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids* would be an effective treatment for early COVID-19 illness.

Methods
We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.

Results
146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care.

Conclusion
Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.

(Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca; ClinicalTrials.gov number, NCT04416399)

Evidence before this study
The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed.

Added value of this study
In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care.

Implications of all the available evidence
The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms...

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* Inhaled corticosteroids are medicines containing corticosteroids such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone in a preparation designed to be inhaled through the mouth. Inhaled corticosteroids act directly in the lungs to inhibit the inflammatory process that causes asthma. https://www.drugs.com/drug-class/inhaled-corticosteroids.html

Antibodies to seasonal coronaviruses may not have any impact on SARS-CoV-2, but maybe the reverse?
" Antibodies to a related betacoronavirus are boosted upon SARS-CoV-2 infection. "

Childhood Colds Do Not Prevent Coronavirus Infection, Study Finds
Apoorva Mandavilli | Feb. 10, 2021

New research casts doubt on the idea that prior infections with garden-variety coronaviruses might shield some people, particularly children, amid the pandemic.

The theory was simple and compelling: Children are less vulnerable to the new coronavirus because they carry antibodies to other common coronaviruses that cause the common cold. The idea might also explain why some people infected with the new virus have mild symptoms while others — presumably without antibodies to common cold coronaviruses — are much more severely affected.

The notion gained traction particularly among people who claimed that this existing protection would swiftly bring human populations to herd immunity, the point at which a pathogen’s spread slows to a halt as it runs out of hosts to infect. A study in the journal Science, published in December*, gave the hypothesis a strong boost.

But for all its appeal, the theory does not hold up, according to a new study published on Tuesday in the journal Cell**. Based on carefully conducted experiments with live virus and with hundreds of blood samples drawn before and after the pandemic, the new research refutes the idea that antibodies to seasonal coronaviruses have any impact on the new coronavirus, called SARS-CoV-2...

https://www.nytimes.com/2021/02/10/health/coronavirus-colds-immunity.html

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* Kevin W. Ng et al. 2021. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science 11 Dec 2020: Vol. 370, Issue 6522, pp. 1339-1343 DOI: 10.1126/science.abe1107 https://science.sciencemag.org/content/370/6522/1339

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** Elizabeth M. Anderson et al. 2021. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell (February 09, 2021) DOI:https://doi.org/10.1016/j.cell.2021.02.010 https://www.cell.com/cell/fulltext/S0092-8674(21)00160-4

Highlights
• Some humans possessed cross-reactive SARS-CoV-2 antibodies prior to the pandemic
• Pre-pandemic SARS-CoV-2 reactive antibodies are not associated with protection
• Antibodies to a related betacoronavirus are boosted upon SARS-CoV-2 infection

Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection...

A Few Covid Vaccine Recipients Developed a Rare Blood Disorder
A link to the vaccines is not certain, and investigations are underway in some reported cases.
Denise Grady | Feb. 8, 2021

...More than 31 million people in the United States have received at least one (mRNA COVID vaccine) dose, and 36...cases (immune thrombocytopenia — a lack of platelets, a blood component essential for clotting) had been reported to the government’s Vaccine Adverse Event Reporting System, VAERS, by the end of January. The cases involved either the Pfizer-BioNTech or Moderna vaccine, the only two authorized so far for emergency use in the United States.

...Hematologists with expertise in treating immune thrombocytopenia said they suspected that the vaccine did play a role. But they said that cases after vaccination were likely to be exceedingly rare, possibly the result of an unknown predisposition in some people to react to the vaccine by developing an immune response that destroys their platelets. The disorder has occurred, rarely, in people who received other inoculations, particularly the measles-mumps-rubella one.

...In its most common form, immune thrombocytopenia is an autoimmune disease that affects about 50,000 people in the United States, according to a support group for patients. The condition develops when the immune system attacks platelets or the cells that create them, for unknown reasons. It sometimes follows a viral illness, and can persist for months or become chronic and last for years. It is generally treatable. Professional groups have advised that patients with the disorder be vaccinated for Covid, but after consulting with their hematologists...

https://www.nytimes.com/2021/02/08/health/immune-thrombocytopenia-covid-vaccine-...

Yah think? :/

A new California variant may be driving the virus surge in the state, a study suggests.
NYT | updated Feb 4, 2021

...California...produced a variant of its own.

That mutant, which belongs to a lineage known as CAL.20C, seemed to have popped up in July but lay low till November. Then it began to quickly spread.

CAL.20C accounted for more than half of the virus genome samples collected in Los Angeles laboratories on Jan. 13, according to a new study that has not yet been published.

...There’s no evidence that CAL.20C is more lethal than other variants. And scientists have to conduct more research to determine whether CAL.20C is in fact more contagious.

But Eric Vail, the director of molecular pathology at Cedars-Sinai, said it was possible that CAL.20C was playing a large part in the surge of cases that has overwhelmed Southern California’s hospitals. “I’m decently confident that this is a more infectious strain of the virus,” Dr. Vail said.

Dr. Charles Chiu, a virologist at the University of California, San Francisco, said that across the state, he and his colleagues were finding the variant in roughly 20 percent to 30 percent of samples being sequenced. “It just popped up under our noses, and now it’s rising in multiple counties,” he said. “On the whole, it’s safe to say it’s going to spread outside of California.”

Researchers are also looking in other states for CAL.20C, Dr. Plummer said, and have so far found it in Arizona, Connecticut, Maryland, New Mexico, Nevada, New York, Texas, Utah, Washington and Wyoming, as well as the District of Columbia. It’s not clear yet how common it is outside California.

A spokesman for the Centers for Disease Control and Prevention said the agency was working with California to learn more about the new variant. “Currently, it’s not known whether this variant is any different from other SARS-CoV-2 viruses, whether those differences may have contributed to its emergence, or whether this emergence was merely a random event,” he said.

...Dr. Chiu and his colleagues are now growing the variant in cells to see how quickly they multiply compared with other variants. The researchers are also going to observe how well antibodies produced by vaccines work against CAL.C20...

https://www.nytimes.com/live/2021/01/19/world/covid-19-coronavirus#a-new-califor...

>1 margd: that last point is crucial: when did they get infected? I wonder if antibody testing has been done (it must, right?)

>13 stellarexplorer: Amazed to read today that a 116 year old survived COVID-19!
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Medical procedure masks' performance greatly enhanced by combining with cloth mask or knotting-and tucking!

Brooks JT, Beezhold DH, Noti JD, et al. Maximizing Fit for Cloth and Medical Procedure Masks to Improve Performance and Reduce SARS-CoV-2 Transmission and Exposure, 2021. MMWR Morb Mortal Wkly Rep. ePub: 10 February 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7007e1 https://www.cdc.gov/mmwr/volumes/70/wr/mm7007e1.htm?s_cid=mm7007e1_w

...What is added by this report?
CDC conducted experiments to assess two ways of improving the fit of medical procedure masks: fitting a cloth mask over a medical procedure mask, and knotting the ear loops of a medical procedure mask and then tucking in and flattening the extra material close to the face. Each modification substantially improved source control and reduced wearer exposure.

What are the implications for public health?
These experiments highlight the importance of good fit to maximize mask performance. There are multiple simple ways to achieve better fit of masks to more effectively slow the spread of COVID-19.

...Results from the first experiment demonstrated that the unknotted medical procedure mask alone blocked 42.0% of the particles from a simulated cough..., and the cloth mask alone blocked 44.3% .... The combination of the cloth mask covering the medical procedure mask (double mask) blocked 92.5% of the cough particles.

In the second experiment, adding a cloth mask over the source headform’s medical procedure mask or knotting and tucking the medical procedure mask reduced the cumulative exposure of the unmasked receiver by 82.2% and 62.9%..., respectively (Figure 2). When the source was unmasked and the receiver was fitted with the double mask or the knotted and tucked medical procedure mask, the receiver’s cumulative exposure was reduced by 83.0%... and 64.5%... , respectively. When the source and receiver were both fitted with double masks or knotted and tucked masks, the cumulative exposure of the receiver was reduced 96.4%...and 95.9%..., respectively.

>14 margd: while that is amazing, it is worth noting that there is no age beyond which a person has a higher chance of dying than living after contracting Covid. The highest death rate I can find in the group older than 85 is in Italy, at about 20%. It’s 13% in S Korea.

Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines' activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination--found in UK (B.1.1.7/501Y.V1), South Africa (B.1.351/501Y.V2) and Brazil (P.1)variants-- was reduced by a small but significant margin. "..it is possible that these mutations and others that emerge in individuals with suboptimal or waning immunity will erode the effectiveness of natural and vaccine elicited immunity. The data suggests that SARS-CoV-2 vaccines and antibody therapies may need to be updated and immunity monitored in order to compensate for viral evolution."

Wang, Z., Schmidt, F., Weisblum, Y. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature (10 February 2021). https://doi.org/10.1038/s41586-021-03324-6 https://www.nature.com/articles/s41586-021-03324-6

This is an unedited manuscript that has been accepted for publication.

Abstract
Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines... Eight weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection.... However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors... However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

...Discussion
The mRNA-based SARS-CoV-2 vaccines are safe and effective and being deployed globally to prevent infection and disease. The vaccines elicit antibody responses against the RBD, the major target of neutralizing antibodies..., in a manner that resembles natural infection. Notably, the neutralizing antibodies produced by mRNA vaccination target the same epitopes as natural infection. The data are consistent with SARS-CoV-2 spike trimers translated from the injected RNA adopting a range of different conformations. Moreover, different individuals immunized with either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines produce closely related and nearly identical antibodies. Whether or not neutralizing antibodies to epitopes other that RBD are elicited by vaccination remains to be determined.

Human neutralizing monoclonal antibodies to the SARS-CoV-2 RBD can be categorized as belonging to 4 different classes based on their target regions on the RBD7. Class 1 and 2 antibodies are among the most potent and also the most abundant antibodies.... These antibodies target epitopes that overlap or are closely associated with RBD residues K417, E484 and N501. They are frequently sensitive to mutation in these residues and select for K417N, E484K and N501Y mutations in SARS-CoV-2 S protein expression libraries in yeast and VSV13,16,32. To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes...

A number of circulating SARS-CoV-2 variants that have been associated with rapidly increasing case numbers and have particular prevalence in the UK (B.1.1.7/501Y.V1), South Africa (B.1.351/501Y.V2) and Brazil (P.1).... Our experiments indicate that the RBD mutations found in these variants, and potentially others that carry K417N/T, E484K and N501Y mutations, can reduce the neutralization potency of vaccinee and convalescent plasma against SARS-CoV-2 pseudotyped viruses. Although our assays are limited to pseudotyped viruses there is an excellent correlation between pseudotyped and authentic SARS-CoV-2 neutralization assays... In addition, similar results have been reported by others using vaccinee and convalescent plasmas and a variety of different pseudotype and authentic virus assays...

The comparatively modest effects of the mutations on viral sensitivity to plasma reflects the polyclonal nature of the neutralizing antibodies in vaccinee plasma. Nevertheless, emergence of these particular variants is consistent with the dominance of the class 1 and 2 antibody response in infected or vaccinated individuals. We speculate that these mutations emerged in response to immune selection in individuals with non-sterilizing immunity. What the long-term effect of accumulation of mutations on the SARS-CoV-2 pandemic will be is not known, but the common cold coronavirus HCoV-229E evolves antigenic variants that are comparatively resistant to the older sera but remain sensitive to contemporaneous sera49. Thus, it is possible that these mutations and others that emerge in individuals with suboptimal or waning immunity will erode the effectiveness of natural and vaccine elicited immunity. The data suggests that SARS-CoV-2 vaccines and antibody therapies may need to be updated and immunity monitored in order to compensate for viral evolution.

COVID-19 vaccines: What does 95% efficacy actually mean?
Anna Nowogrodzki Feb 11, 2021

It doesn't mean 5% of vaccinated people get infected.

...What the 95% actually means is that vaccinated people had a 95% lower risk of getting COVID-19 compared with the control group participants, who weren't vaccinated. In other words, vaccinated people in the Pfizer clinical trial were 20 times less likely than the control group to get COVID-19.

That makes the vaccine "one of the most effective vaccines that we have," (Brianne Barker, a virologist at Drew University in New Jersey) told Live Science. For comparison, the two-dose measles, mumps and rubella (MMR) vaccine is 97% effective against measles and 88% effective against mumps... The seasonal flu vaccine is between 40% and 60% effective (it varies from year to year, depending on that year's vaccine and flu strains), but it still prevented an estimated 7.5 million cases of the flu in the U.S. during the 2019-2020 flu season...

So, if efficacy means some percent fewer cases of COVID-19, what counts as a "case of COVID"? Both Pfizer and Moderna defined a case as having at least one symptom (however mild) and a positive COVID-19 test...Someone with a moderate case of COVID-19 by this definition could either be mildly affected or be incapacitated and feel pretty sick for a few weeks...

...Barker cautions that it’s tricky to directly compare efficacy between the Johnson & Johnson, Pfizer, and Moderna vaccines, because the clinical trials happened in different geographic areas with different populations, and at slightly different time points in the pandemic when different variants of COVID-19 were circulating.

...All three vaccines were 100% effective at preventing severe disease six weeks after the first dose (for Moderna) or seven weeks after the first dose (for Pfizer and Johnson & Johnson, the latter of which requires only one dose). Zero vaccinated people in any of the trials were hospitalized or died of COVID-19 after the vaccines had fully taken effect...

https://www.livescience.com/covid-19-vaccine-efficacy-explained.html

"...Early initiation (within 24 hours of (hospital) admission) of prophylactic anticoagulation (subcutaneous heparin or enoxaparin*) compared with no anticoagulation... was associated with a (27%) decreased risk of 30 day mortality and no increased risk of serious bleeding events."

* heparin injection, e.g., before surgery ( https://www.drugs.com/heparin.html )
enoxaparin--treats Deep Vein Thrombosis ( https://www.webmd.com/drugs/2/drug-3475/enoxaparin-subcutaneous/details )

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Blood thinners and improved survival from covid-19.
"These findings provide strong real world evidence to support ...'
prophylactic anticoagulation as initiative treatment for patients with covid-19 on hospital admission"

Image-30d mortality v hospital daays w & w/o anticoagulants
( https://twitter.com/EricTopol/status/1360234337623412739/photo/1 )

- Eric Topol ("physician-scientist") @EricTopol | 9:28 AM · Feb 12, 2021
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https://bmj.com/content/372/bmj.n311

Christopher T Rentsch et al. 2021. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ 11 February 2021; 372:n311. doi: https://doi.org/10.1136/bmj.n311

Abstract
...Results
Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% ... among those who received prophylactic anticoagulation and 18.7% ... among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73...). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87...). Quantitative bias analysis showed that results were robust to unmeasured confounding... Results persisted in several sensitivity analyses.

Conclusions
Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

...Comparison with other evidence
...Thromboembolic events in the context of covid-19 are strongly associated with mortality... The cause of elevated thrombosis risk remains unclear, although proposed mechanisms have included systemic inflammation, endothelialitis, and activation of the complement system... Increases in a variety of inflammatory pathways, including bradykinin, interleukin 6, C reactive protein, and growth differentiation factor..., have been described in covid-19... Further, heparin has been shown to block the SARS-CoV-2 viral spike protein from binding in experimental studies... We postulate that the combination of the known antithrombotic and potential anti-inflammatory effects of heparin,... in addition to attenuation of viral infectivity might, at least in part, explain the observed benefit associated with prophylactic anticoagulation.

...Conclusions and implications
We studied a nationwide cohort of patients admitted to hospital with covid-19 and found that initiation of prophylactic, heparin based anticoagulation compared with no anticoagulation within 24 hours of admission was associated with a lower risk of 30 day mortality, in-hospital mortality, and initiation of therapeutic anticoagulation probably indicative of clinical deterioration, including thromboembolic events. This benefit seemed to be greater among patients not admitted to the ICU within 24 hours of hospital admission. Early initiation of prophylactic anticoagulation was not associated with an increased risk of bleeding that required transfusion. Our results provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

>18 margd: this result is influencing clinical practice

US could have averted 40% of Covid deaths, says panel examining Trump's policies
Amanda Holpuch | Thu 11 Feb 2021

...Dr Mary T Bassett, a commission member and director of Harvard University’s FXB Center for Health and Human Rights, told the Guardian: “The US has fared so badly with this pandemic, but the bungling can’t be attributed only to Mr Trump, it also has to do with these societal failures … That’s not going to be solved by a vaccine.”

In a wide-ranging assessment published on Thursday, the commission said Trump “brought misfortune to the USA and the planet” during his four years in office. The stinging critique not only blamed Trump, but also tied his actions to the historical conditions which made his presidency possible.

“He was sort of a crowning achievement of a certain period but he’s not the only architect,” said Bassett, “And so we decided it’s important to put him in context, not to minimize how destructive his policy agenda has been and his personal fanning the flames of white supremacy, but to put it in context.”

The commission condemned Trump’s response to Covid, but emphasized that the country entered the pandemic with a degraded public health infrastructure. Between 2002 and 2019, US public health spending fell from 3.21% to 2.45% – approximately half the share of spending in Canada and the UK....

https://www.theguardian.com/us-news/2021/feb/10/us-coronavirus-response-donald-t...
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Steffie Woolhandler et al. 2021. Public policy and health in the Trump era. The Lancet (February 10, 2021) DOI:https://doi.org/10.1016/S0140-6736(20)32545-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32545-9/fullt...

GI symptoms associated with COVID-19
Medical News Todya \ Feb 12, 2021

...The research is ever-evolving. But according to a review published this month analyzing 125 articles and a total of 25,252 patients, the most common GI symptoms associated with COVID-19 include:

lack of appetite (19.9%)
lack of smell or taste (15.4%)
diarrhea (13.2%)
nausea (10.3%)
vomiting up blood or GI bleeding (9.1%)

Another review published in late January found much broader ranges of symptom prevalence rates, such as:

diarrhea (9–34%)
nausea, vomiting, or both (7–16%)
abdominal pain (3–11%)

Less commonly, COVID-19 may also cause:

belching
acid reflux
indigestion
colitis, or intestinal inflammation
GI bleeding

The disease may also destroy bowel tissues and reduce intestinal movement.

Right now, it seems most people who experience GI symptoms with COVID-19 develop them alongside respiratory symptoms.

However, a review from late 2020 found around 20% of people with COVID-19 infections only experience GI symptoms. And sometimes, these symptoms develop before respiratory symptoms or fever develop.

Early studies suggest GI symptoms tend to occur during the early stages of the infection. But more research is needed to confirm when GI symptoms develop in COVID-19 cases if there is a specific time frame.

https://www.medicalnewstoday.com/articles/gastrointestinal-symptoms-in-covid-19-...

Updated estimates of coronavirus (COVID-19) related deaths by disability status, England: 24 January to 20 November 2020

Estimates of differences in COVID-19 mortality risk by self-reported disability status and diagnosed learning disability status for deaths occurring up to 20 November 2020, using linked data from the 2011 Census, death registrations, and primary care and hospital records.

Daniel Ayoubkhani and Matt Bosworth | 11 February 2021

1. Main points

Between 24 January and 20 November 2020 in England, the risk of death involving the coronavirus (COVID-19) was 3.1 times greater for more-disabled men and 1.9 times greater for less-disabled men, compared with non-disabled men; among women, the risk of death was 3.5 times greater for more-disabled women and 2.0 times greater for less-disabled women, compared with non-disabled women.

Disability status was self-reported as collected in the 2011 Census; those who said in the Census that their day-to-day activities were “limited a little” or “limited a lot” are referred to here as “less-disabled” and “more-disabled” respectively, whereas people reporting no limitation to their activities are referred to as “non-disabled”.

After using statistical models to adjust for personal and household characteristics, including residence type, geography, demographic and socio-economic factors, and pre-existing health conditions, a smaller but statistically significantly raised risk of death remained unexplained for more-disabled and less-disabled women (1.4 and 1.2 times respectively) and more-disabled men (1.1 times) but not for less-disabled men.

This means that no single factor explains the considerably raised risk of death involving COVID-19 among disabled people, and place of residence, socio-economic and geographical circumstances, and pre-existing health conditions all play a part; an important part of the raised risk is because disabled people are disproportionately exposed to a range of generally disadvantageous circumstances compared with non-disabled people.

Looking at people with a medically diagnosed learning disability, the risk of death involving COVID-19 was 3.7 times greater for both men and women compared with people who did not have a learning disability; after using statistical models to adjust for a range of factors, a raised risk of 1.7 times remained unexplained for both sexes.

All the socio-economic and geographical circumstances and pre-existing health conditions considered made some difference to the risk for people with learning disabilities, but the largest effect was associated with living in a care home or other communal establishment.

Patterns in excess COVID-19 mortality risk experienced by disabled people remained largely unchanged between the first and second waves of the pandemic...

https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/dea...

Israel data suggest that the Pfizer vaccine has led to over a 50% reduction in COVID-19 cases so far
Medical News Today | 02/12/2021

Recent data from Israel, which has vaccinated around 3.5 million people, suggest that the Pfizer-BioNTech vaccine is indeed effective at preventing COVID-19.

...At the time of the analysis, which was publicized on February 7, more than 75% of Israelis aged over 60 and around 25% of those aged 40–60 had received the first dose of the Pfizer-BioNTech vaccine.

“Our findings highlight that vaccination does not only protect the individual who receives it, but is likely to reduce viral shedding and therefore transmission in the population,” the authors of the paper write.

https://www.medicalnewstoday.com/articles/covid-19-vaccine-live-updates

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Ella Petter et al. 2021. Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2.
MedRxiv Feb 8, 2021. doi: https://doi.org/10.1101/2021.02.08.21251329 https://www.medrxiv.org/content/10.1101/2021.02.08.21251329v1

This article is a preprint and has not been certified by peer review

Abstract
One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct* value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual’s protection but can reduce transmission.

...at late December, only 5% of the samples had a variant of concern, while on Jan 18th, about 50% exhibited these variants. From all 57 samples with variants of concern, only 5 were B.1.351 and the rest were B.1.1.7...

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* The cycle threshold (Ct) in reverse transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 tests is gaining currency as a potential marker for severe disease in patients with COVID-19 illness. Ct refers to the number of cycles needed to amplify viral RNA to reach a detectable level. https://www.aacc.org/cln/cln-stat/2020/december/3/sars-cov-2-cycle-threshold-a-m...

Preprint: "A two-dose regimen of ChAdOx1-nCoV19 (chimp adenovirus Oxford-Astrazeneca vaccine) did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, VE (vaccine efficacy) against severe Covid-19 is undetermined."

Shabir A. Madhi et al. 2021. Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. MedRxiv Feb 12, 2021. 26 p. https://doi.org/10.1101/2021.02.10.21251247 https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1.full.pdf

Abstract
Background
Assessingsafety and efficacy of Covid-19 vaccines in different populations is essential, asis investigation of efficacy against emerging SARS-CoV-2 variants of concern including the B.1.351 (501Y.V2)variant first identified in South Africa.

Methods
We conducted a randomized multi-centre, double blinded controlled trial on safety and efficacy of ChAdOx1-nCoV19 in HIV-uninfected people in South Africa. Participants age 18 to less than 65 years randomized (1:1) to two doses of vaccine containing 5x1010 viral particles or placebo (0.9% NaCl) 21-35 days apart. Post 2nd-dose serum samples (n=25) were tested by pseudo-typed (PSVNA) and live virus (LVNA) neutralization assays against the D614G and B.1.351variants. Primary endpoints were safety and vaccine efficacy (VE) greater than 14 days following second dose against laboratory confirmed symptomatic Covid-19.

Results
2026 HIV-uninfected adults were enrolled between June 24th and Nov 9th, 2020; 1010 and 1011 received at least one dose of placebo or vaccine, respectively. Median age was 31 years. The B.1.351 variant showed increased resistance to vaccinee sera using the PSVNA and LVNA. In the primary endpoint analysis, 23/717 (3.2%) placebo and 19/750 (2.5%) vaccine recipients developed mild-moderate Covid-19; VE 21.9% (...). Of the primary endpoint cases, 39/42 (92.9%) were the B.1.351variant; against which VE was 10.4% (...) analyzed as a secondary objective. The incidence of serious adverse events was balanced between the vaccine and placebo groups.

Conclusions
A two-dose regimen of ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, VE against severe Covid-19 is undetermined.

Update of anaphylaxis from mRNA vaccines:
66 cases out of ~18 million vaccinations (= 0.0003%, correction...) (...almost all occur in women...).
All but 1 within 11 minutes. No deaths.
- Eric Topol @EricTopol | 1:41 PM · Feb 12, 2021

Image--Moderna Pfizer VAERS Dec 14-Jan 18( https://twitter.com/EricTopol/status/1360298117493493760/photo/1 )

Tom T. Shimabukuro et al. 2021. Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021. JAMA. Published online February 12, 2021. doi:10.1001/jama.2021.1967 https://jamanetwork.com/journals/jama/fullarticle/2776557

YAY!

Pfizer vaccine found to give strong immune response to new Covid variants
Study finds patients have strong T-cell response after one jab, and second boosts antibody response
Linda Geddes | 11 Feb 2021

People who have received two doses of the Pfizer vaccine have been found to have strong T-cell responses against the Kent and South African variants of Covid, suggesting that the vaccine will continue to protect against serious disease in the coming months.

...William James, a professor of virology at the University of Oxford, and his colleagues took blood samples from people who had recovered from Covid-19, and health workers who had received either one or two doses of the Pfizer/BioNTech vaccine. They also obtained isolates of the B117 and B1.351 virus variants first identified in Kent and South Africa, and of an older variant similar to those circulating a year ago. Antibodies and T cells from the individuals were then tested against these viruses to see how well they performed.

The study, which has not yet been reviewed by other scientists, found that people’s antibodies were moderately effective against the original virus after their first dose of vaccine, less effective against the Kent variant, and were unable to neutralise the South African variant.

However, they had strong T-cell responses against all known variants after the first jab. “It may not necessarily protect you against infection, but it’s very likely that this first dose will make it much easier for your immune system to make a good response the next time around,” said James. “We think this is why that second dose produces such a good strong antibody response, because the T cells are already there, ready to react.”

The discovery that people who have recovered from Covid-19 and those who have received at least one dose of vaccine possess T cells capable of responding to the new variants is encouraging, because it suggests the T cells are recognising different regions of the spike protein to the antibodies. It could imply they will be more resilient to future variants. “It doesn’t promise you won’t get ill from the new variants, but it does suggest there’s something to work from and that your immune system can respond to them,” said James.

People’s antibody responses were also boosted by the second Pfizer jab. “In more than 90% of cases, the antibodies that people are generating after the second dose are up at the sort of level that neutralises the virus and which we would expect to protect them from infection,” said James. “We’re pretty confident that they’ll be protected from infection by the South African strain and the Kent strain, as well as the original strain of the virus...

https://www.theguardian.com/world/2021/feb/11/pfizer-vaccine-strong-response-new...

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Donal T. Skelly et al. 2021. Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern. Research Square Feb 9, 2021. DOI: 10.21203/rs.3.rs-226857/v1 https://www.researchsquare.com/article/rs-226857/v1

This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal.

ABSTRACT
Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.

"In patients hospitalized with COVID-19 (Spain), calcifediol (D3) treatment at the time of hospitalization significantly reduced ICU admission and mortality."

Nogués, Xavier and Ovejero, Diana and Quesada-Gomez, J. M. and Bouillon, Roger and Arenas, Dolores and Pascual, Julio and Villar-Garcia, Judith and Rial, Abora and Gimenez-Argente, Carme and Cos, ML. and Rodriguez-Morera, Jaime and Campodarve, Isabel and Guerri-Fernandez, Robert and Pineda-Moncusí, Marta and García-Giralt, Natalia, Calcifediol Treatment and COVID-19-Related Outcomes. Available at SSRN: https://ssrn.com/abstract=3771318 or http://dx.doi.org/10.2139/ssrn.3771318

Preprints with The Lancet.

Abstract
Background...

Methods: Our study aims to elucidate the effect of calcifediol 25(OH)D3 treatment on ICU admission and mortality, in patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug* on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379).

Findings: ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%...). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25(OH)D levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (RR 0.18... ). Baseline 25(OH)D levels inversely correlated with the risk of ICU admission (RR 0.53 ...). Overall mortality was 10%. In the Intention-to-treat analysis, 36 (6.5%) out of 551 patients treated with calcifediol at admission died compared to 57 patients (15%) out of 379 controls...). Adjusted results showed a reduced mortality for more of 60%. Higher baseline 25(OH)D levels were significantly associated with decreased mortality... Age and obesity were also predictors of mortality.

Interpretation: In patients hospitalized with COVID-19, calcifediol treatment at the time of hospitalization significantly reduced ICU admission and mortality...

* 1 mcg vitamin D is equal to 40 IU ( https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ )

>27 margd: Wow! Seems significant

> 28

Spaniards on average tend to be a little deficient in D*, so effect might be more pronounced there?
All nations have people who are deficient, though--homebound, elderly, dark-skinned, northerners--and they might be more represented in ICUs, etc.?

Good time to be sure that one has sufficient D from sun, diet, or supplements, I think!
Unless on Warfarin etc., not bad idea to take D3K2 formulation--to direct Ca to bones and not soft tissue.
(Remember study a while back that showed ~ men with adequate fiber metabolized D better?)
The amounts in the study are therapeutic--too big as a daily supplement.

* https://revista-fi.com.br/upload_arquivos/201606/2016060068176001464973585.pdf

Interesting introduction on seasonality of respiratory viruses, including SARS-CoV-2. (I've read that mountain people of all races have high-bridged noses, purportedly to humidify the arid mountain air. Respiratory disease might have been selection factor?)

Researchers propose that humidity from masks may lessen severity of COVID-19
Lisa Yuan | Friday, February 12, 2021

...researchers in the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), found that face masks substantially increase the humidity in the air that the mask-wearer breathes in. This higher level of humidity in inhaled air, the researchers suggest, could help explain why wearing masks has been linked to lower disease severity in people infected with SARS-CoV-2, because hydration of the respiratory tract is known to benefit the immune system.

...High levels of humidity can limit the spread of a virus to the lungs by promoting mucociliary clearance (MCC), a defense mechanism that removes mucus − and potentially harmful particles within the mucus − from the lungs. High levels of humidity can also bolster the immune system by producing special proteins, called interferons, that fight against viruses − a process known as the interferon response. Low levels of humidity have been shown to impair both MCC and the interferon response, which may be one reason why people are likelier to get respiratory infections in cold weather.

The study tested four common types of masks: an N95 mask, a three-ply disposable surgical mask, a two-ply cotton-polyester mask, and a heavy cotton mask...all four masks increased the level of humidity of inhaled air, but to varying degrees. At lower temperatures, the humidifying effects of all masks greatly increased. At all temperatures, the thick cotton mask led to the most increased level of humidity.

“The increased level of humidity is something most mask-wearers probably felt without being able to recognize, and without realizing that this humidity might actually be good for them,” Bax said.

The researchers did not look at which masks are most effective against inhalation or transmission of the virus and defer to the CDC for guidance on choosing a mask ( https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/diy-cloth-face-co... )... While the current study did not examine respiratory droplets, it does offer more evidence as to why masks are essential to battling COVID-19...

https://www.nih.gov/news-events/news-releases/researchers-propose-humidity-masks...

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ETA: paper now published.

Courtney, JM and Bax, A. Hydrating the respiratory tract: An alternative explanation why masks lower severity of COVID-19 disease. Biophysical Journal. February 11, 2021. DOI:https://doi.org/10.1016/j.bpj.2021.02.002 https://www.cell.com/biophysj/fulltext/S0006-3495(21)00116-8

Abstract
Seasonality of respiratory diseases has been linked, among other factors, to low outdoor absolute humidity and low indoor relative humidity, which increase evaporation of water in the mucosal lining of the respiratory tract. We demonstrate that normal breathing results in an absorption-desorption cycle inside facemasks, where super-saturated air is absorbed by the mask fibers during expiration, followed by evaporation during inspiration of dry environmental air. For double-layered cotton masks, which have considerable heat capacity, the temperature of inspired air rises above room temperature, and the effective increase in relative humidity can exceed 100%. We propose that the recently reported, disease-attenuating effect of generic facemasks is dominated by the strong humidity increase of inspired air. This elevated humidity promotes mucociliary clearance of pathogens from the lungs, both before and after an infection of the upper respiratory tract has occurred. Effective mucociliary clearance can delay and reduce infection of the lower respiratory tract, thus mitigating disease severity. This mode of action suggests that masks can benefit the wearer even after an infection in the upper respiratory tract has occurred, complementing the traditional function of masks to limit person-to-person disease transmission. This potential therapeutical use should be studied further.

ETA: https://twitter.com/EricTopol/status/1344032029390766080/photo/1

ETA: explainer 1:50 ( https://www.youtube.com/watch?v=34oCDtiTNcA&feature=youtu.be )

UK Coronavirus Variant May Be Up to 70% Deadlier, New Evidence Suggests
KELSEY VLAMIS | 15 FEBRUARY 2021

The coronavirus variant that originated in the United Kingdom is likely deadlier than the original strain, according to a new assessment released on Friday by British government scientists.*

In the report, which evaluated multiple studies, the scientists estimated that the strain, known as B.1.1.7, could be 30 percent to 70 percent deadlier than the original virus.

...the more contagious variant has been circulating throughout the world and the US. It has been detected in at least 82 countries...A study** published earlier this month found the UK variant was spreading so quickly across the US that the case count involving that strain was doubling about every ten days..."...B.1.1.7 will likely become the dominant variant in many US states by March 2021, leading to further surges of COVID-19 in the country, unless urgent mitigation efforts are immediately implemented,"

The study also said the UK variant is 35 percent to 45 percent more transmissible than other strains spreading in the US. Scientists have also expressed concern that the variant could be developing a mutation that would help it evade vaccines.

It is not yet clear why the UK variant may have a higher mortality rate...

* 13 p summary ( https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attac... )

** https://www.medrxiv.org/content/10.1101/2021.02.06.21251159v1

https://www.sciencealert.com/new-uk-coronavirus-variant-could-be-more-lethal-new...

SARS-CoV-2: "Check"?

7 Virus Variants Found in U.S. Carrying the Same Mutation
Scientists don’t know yet whether the mutation makes the variants more contagious, but they are concerned that it might.
Carl Zimmer | Feb. 14, 2021

...researchers reported seven growing lineages of the novel coronavirus, spotted in states across the country. All of them have (independently) evolved a mutation in the same genetic letter (677).

...It’s unclear whether it makes the variants more contagious. But because the mutation appears in a gene that influences how the virus enters human cells, the scientists are highly suspicious.

...It’s difficult to answer even basic questions about the prevalence of these seven lineages because the United States sequences genomes from less than 1 percent of coronavirus test samples.

...It’s also hard to say whether the increase in variants is actually the result of their being more contagious. They might have become more common simply because of all of the travel over the holiday season. Or they might have exploded during superspreader events at bars or factories....

https://www.nytimes.com/2021/02/14/health/coronavirus-variants-evolution.html

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Fig.4 Linear-specific and shared polymorphisms of US variants... ( https://twitter.com/DrEricDing/status/1361300279203946497/photo/1 )
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Emma B Hodcroft et al. 2021. Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677. MedRxiv Feb 14, 2021. doi: https://doi.org/10.1101/2021.02.12.21251658 https://www.medrxiv.org/content/10.1101/2021.02.12.21251658v1

This article is a preprint and has not been certified by peer review

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, ACE2. Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid August to late November, 2020. Four 677H clades from clade 20G (B.1.2) , 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.

COVID-19 shots might be tweaked if variants get worse
LAURAN NEERGAARD | 2/15/2021

..Viruses mutate constantly and it takes just the right combination of particular mutations to escape vaccination. But studies are raising concern that first-generation COVID-19 vaccines don’t work as well against a mutant that first emerged in South Africa as they do against other versions circulating around the world.

The good news: Many of the new COVID-19 vaccines are made with new, flexible technology that’s easy to upgrade. What’s harder: Deciding if the virus has mutated enough that it’s time to modify vaccines — and what changes to make.

...The WHO and FDA are looking to the global flu vaccine system in deciding how to handle similar decisions about COVID-19 shots.

Influenza mutates much faster than the coronavirus, and flu shots have to be adjusted just about every year. National centers around the globe collect circulating flu viruses and track how they’re evolving. They send samples to WHO-designated labs for more sophisticated “antigenic” testing to determine vaccine strength. The WHO and regulators then agree on the year’s vaccine recipe and manufacturers get to work.

... If fully immunized people start getting hospitalized with mutated virus, “that’s when the line gets crossed,” said Dr. Paul Offit, a Children’s Hospital of Philadelphia vaccine expert who advises the FDA.

...First-generation COVID-19 vaccines were tested in tens of thousands of people to be sure they work and are safe — research that took many months...FDA still is finalizing requirements, but (Dr. Peter Marks, the FDA’s vaccine chief) said the agency intends to “be pretty nimble.” If an updated vaccine is needed, tests in a few hundred people likely would be enough to tell if it triggers a good immune response, he said...

https://apnews.com/article/flu-united-nations-coronavirus-pandemic-coronavirus-v...

"adaptive immunity following natural infection of SARS-CoV-2 might persist for at least 6-8 months, regardless of disease severity. Development of medium or long-term protective immunity through vaccination might thus be possible."

Sherina, N. et al. 2021. Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection, Med (2021), doi: https://doi.org/10.1016/j.medj.2021.02.001 https://www.cell.com/med/pdf/S2666-6340(21)00038-6.pdf

This version will undergo additional copyediting, typesetting and review before it is published in its final form.

Summary
Background
Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody levels and specific memory B- and T-cell responses in convalescent coronavirus disease-2019 (COVID-19) patients.

Methods
Altogether 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, level of SARS-CoV-2 neutralizing antibodies, specific memory B- and T-cell responses were tested in a subset of samples.

Findings
Anti-SARS-CoV-2 antibodies were present in 85% of the samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM/IgA antibodies declined after 1 month while levels of specific IgG antibodies and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses developed with time and were persistent in all patients followed up till 6-8 months.

Conclusions
Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 might persist for at least 6-8 months, regardless of disease severity. Development of medium or long-term protective immunity through vaccination might thus be possible...

https://twitter.com/DrEricDing/status/1361652863043305473/photo/1

___________________________________________________________

Immunoglobulin A: IgA antibodies are found in the mucous membranes of the lungs, sinuses, stomach, and intestines. They're also in fluids these membranes produce, like saliva and tears, as well as in the blood.

Immunoglobulin G: IgG is the most common type of antibody in your blood and other body fluids. These antibodies protect you against infection by "remembering" which germs you've been exposed to before. If those germs come back, your immune system knows to attack them. Your doctor can test for IgG to figure out whether you've been infected by certain kinds of bacteria or virus.

Immunoglobulin M: Your body makes IgM antibodies when you are first infected with new bacteria or other germs. They are your body's first line of defense against infections. When your body senses an invader, your IgM level will rise for a short time. It will then begin to drop as your IgG level kicks in and increases to protect you long-term.

https://www.webmd.com/a-to-z-guides/immunoglobulin-test#1

>34 margd: This supports a conversation Ive been having for months: “I had Covid but I have no measurable antibodies”.
“Yes, but you have T and B cells that are primed to respond again to the same challenge should you be reexposed.”
Annoyingly the paper doesn’t specifically say where the patients were from (I assume Italy as it was funded by Italian organizations) nor does it confirm that these results were from the world dominant strain and not one of the variants (and did they even study that?)

So this makes sense, although we still need to account for the unexpected possible lesser protection after illness with the B.1.351 variant.

https://www.huffpost.com/entry/dan-david-prize-anthony-fauci_n_602b59bec5b674159...
Dr. Anthony Fauci Wins $1 Million Prize For ‘Speaking Truth To Power’ On COVID-19

. . . The awards committee of the Dan David Prize, which is affiliated with Tel Aviv University, praised Fauci for “speaking truth to power” amid the pandemic, and “courageously defending science in the face of uninformed opposition during the challenging COVID crisis.” The committee also hailed the director of the National Institute of Allergy and Infectious Diseases as the “consummate model of leadership and impact in public health.”

A well-deserved honor in an era of timid followers!

Covid-19: Vaccine as good in 'real world' as in trial in Israel (BBC)

More data from Israel's vaccination programme is suggesting the Pfizer jab prevents 94% of symptomatic infections. This indicates the vaccine is performing just as well in a larger population as it did in the clinical trials. It is proving highly effective at preventing illness and severe disease among all age groups, according to public health doctor Prof Hagai Levine. "High vaccination coverage of the most susceptible groups" was key, he said...

94% fewer infections among the vaccinated group... And the vaccine prevented almost all cases of serious illness...

02/16/2021 10:41 GMT — WHO authorize AstraZeneca COVID vaccine for emergency use

The World Health Organization (WHO) have announced that they are granting the AstraZeneca COVID-19 vaccine emergency approval. Millions of doses are now likely to be sent to the world’s most vulnerable people as part of COVAX, which is a global initiative aimed at equitable access to COVID-19 vaccines.

“Countries with no access to vaccines to date will finally be able to start vaccinating their health workers and populations at risk,” said Dr. Mariângela Simão, assistant director general for Access to Medicines and Health Products at the WHO.

https://www.medicalnewstoday.com/articles/covid-19-vaccine-live-updates

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WHO lists two additional COVID-19 vaccines for emergency use and COVAX roll-out
AstraZeneca/Oxford-developed vaccines to reach countries in the coming weeks
15 February 2021 News release

...The vaccine was reviewed on 8 February by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE), which makes recommendations for vaccines’ use in populations (i.e. recommended age groups, intervals between shots, advice for specific groups such as pregnant and lactating women). The SAGE recommended the vaccine for all age groups 18 and above.

The AstraZeneca/Oxford product is a viral vectored vaccine called ChAdOx1-S recombinant. It is being produced at several manufacturing sites, as well as in the Republic of Korea and India. ChAdOx1-S has been found to have 63.09% efficacy and is suitable for low- and middle-income countries due to easy storage requirements.
WHO emergency use listing...

WHO also listed the Pfizer/BioNTech vaccine for emergency use on 31 December 2020.

https://www.who.int/news/item/15-02-2021-who-lists-two-additional-covid-19-vacci...

"Our results show that therapeutic and prophylactic administration of EIDD-2801 (molnupiravir), an oral broad spectrum antiviral currently in phase II–III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19."

COVID-19: Antiviral prevents and treats infection in lab tests
James Kingsland | Feb 12, 2021

A study in mice found that molnupiravir (EIDD-2801, originally developed to treat influenza) halted the replication of SARS-CoV-2 — the virus that causes COVID-19 — in grafts of human lung tissue.

The drug also prevented infection when administered 12 hours before exposure to the virus.

Clinical trials of the drug are ongoing to evaluate its safety in humans and whether it can make patients with COVID-19 less infectious.

Previous research suggests that the drug could work against a range of coronaviruses that originate in bats, providing protection in future outbreaks...

https://www.medicalnewstoday.com/articles/covid-19-antiviral-prevents-and-treats...
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Angela Wahl e4t al. 2021. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801.
Nature (09 February 2021). https://www.nature.com/articles/s41586-021-03312-w

This is an unedited manuscript that has been accepted for publication.

Abstract
All known recently emerged human coronaviruses probably originated in bats... Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbour endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for coronavirus infection. Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II–III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19.

Eric Topol (physician-scientist) @EricTopol | 11:42 AM · Feb 16, 2021
Everything you want to know on the 3 major #SARSCoV2 variants in 1 page! by
@13pt and @carlzimmer @NYTScience

Image--New Mutations, New Variants. NYT ( https://twitter.com/EricTopol/status/1361717696061038597/photo/1 )

Interesting. My opthalmologist scans my retinas 2x year (~ Nov & May). I THINK I had COVID in Feb 2020. After my illness, my visual acuity & distance vision dimmed for several months and then recovered. I THINK this was reflected in my Rx. He found no change in my retinal scans.

Eric Topol @EricTopol | 12:06 PM · Feb 16, 2021:
A report of abnormal eye findings by magnetic resonance imaging in 9 patients with severe covid-19,
all with nodules in the macular region, representing 7% of a retrospective consecutive series
@radiology_rsna

https://pubs.rsna.org/doi/10.1148/radiol.2021204394 * ...
Image: retina ( https://twitter.com/EricTopol/status/1361723631051497472/photo/1 )

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Augustin Lecler et al. 2021. Ocular MRI Findings in Patients with Severe COVID-19: A Retrospective Multicenter Observational Study. Radiology. Published Online:Feb 16 2021 https://doi.org/10.1148/radiol.2021204394 https://pubs.rsna.org/doi/10.1148/radiol.2021204394

Abstract
COVID-19 may affect various organs. This paper reports 9 patients (1/9 (11%) woman and 8/9 (89%) men, mean age 56 ± 13 years) with globe MRI abnormalities obtained from a multicenter cohort of 129 patients presenting with severe COVID-19 from March 4th to May 1st, 2020. 9/129 (7%) patients had one or several FLAIR-WI hyperintense nodules of the posterior pole of the globe. All patients had nodules in the macular region, 8/9 (89%) had bilateral nodules, 2/9 (22%) had nodules outside the macular region. Screening of these patients might improve the management of potentially severe ophthalmological manifestations of the virus.

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Editorial:

Claudia F.E. Kirsch 2021. The Eyes Have It: Looking Carefully at the Orbits and SARS-COV-2. Radiology. Published Online:Feb 16 2021https://doi.org/10.1148/radiol.2021210058 https://pubs.rsna.org/doi/10.1148/radiol.2021210058 https://pubs.rsna.org/doi/10.1148/radiol.2021204394

...This important Radiology article is the first to present the MRI ocular imaging disease manifestations of COVID-19. Ocular pathology from the SARS-CoV-2 virus often signifies a more severe disease process and may be occurring with greater prevalence than currently reported and visually underappreciated on current MRI. By publishing this article, the authors will help others appreciate and recognize this critical ocular MRI finding. A true hallmark of a “landmark” article is one that recognizes and reports on a critical finding not yet reported, elucidates the findings so that others can see and find it, and helps improve outcomes for patients. This article reminds all radiologists to pay attention to the orbits on MRI, especially in patients critically ill with COVID-19 admitted to intensive care. The paper identifies where the orbital nodular macular pathology occurs and how best to appreciate it while highlighting potential disease mechanisms, enhancing our understanding of the COVID-19 disease process, and hopefully leading to improved outcomes for all affected in this pandemic.

https://pubs.rsna.org/doi/10.1148/radiol.2021210058

>35 stellarexplorer: No tests when DH and I THOUGHT we had COVID. Months later no antibodies when we gave blood.

It's been over a year and we're now scheduled for vaccine. I've heard that most side effects with first dose if one's been previously been exposed. It would be REALLY good news if our immune systems can still recognize the virus? (IF we had it...)

"In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease...it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y."

Svante Pääbo et al. 2021. A genomic region associated with protection against severe COVID-19 is inherited from Neandertals. PNAS March 2, 2021 118 (9) e2026309118; https://doi.org/10.1073/pnas.2026309118

Significance
We show that a haplotype on chromosome 12, which is associated with a ∼22% reduction in relative risk of becoming severely ill with COVID-19 when infected by SARS-CoV-2, is inherited from Neandertals. This haplotype is present at substantial frequencies in all regions of the world outside Africa. The genomic region where this haplotype occurs encodes proteins that are important during infections with RNA viruses.

Abstract
It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.

"SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS CoV-2’s increased transmissibility."

Eric Topol (physician-scientist) @EricTopol | 9:41 AM · Feb 17, 2021:
We thought B.1.1.7's increased infectiousness was due to higher viral load.
New data from NBA players and staff, with frequent sampling, suggests
it's related to delayed clearance, longer duration of infections...

https://dash.harvard.edu/handle/1/37366884 *

Image--clearance, duration of original v B117 ( https://twitter.com/EricTopol/status/1362049551490637834/photo/1 )
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Dr. Angela Rasmussen (virologist, Georgetown) @angie_rasmussen | 10:13 AM · Feb 17, 2021:
Interesting. A longer interval of contagiousness has always been a possible explanation for increased variant transmissibility.
But this is also n=7, so this is by no means settled,
nor are other hypothetical mechanisms (more shedding, more infectivity, more stability) excluded.

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Kissler, Stephen, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Mallery I. Breban, et al. "Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2." Preprint, 2021. https://dash.harvard.edu/handle/1/37366884 https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37366884

Abstract
To test whether acute infection with B.1.1.7 is associated with higher or more sustained nasopharyngeal viral concentrations, we assessed longitudinal PCR tests performed in a cohort of 65 individuals infected with SARS-CoV-2 undergoing daily surveillance testing, including seven infected with B.1.1.7. For individuals infected with B.1.1.7, the mean duration of the proliferation phase was 5.3 days..., the mean duration of the clearance phase was 8.0 days..., and the mean overall duration of infection (proliferation plus clearance) was 13.3 days... These compare to a mean proliferation phase of 2.0 days... , a mean clearance phase of 6.2 days... , and a mean duration of infection of 8.2 days ... for non-B.1.1.7 virus. The peak viral concentration for B.1.1.7 was 19.0 Ct ... compared to 20.2 Ct ... for non-B.1.1.7. This converts to 8.5 log10 RNA copies/ml ... for B.1.1.7 and 8.2 log10 RNA copies/ml ... for non-B.1.1.7. These data offer evidence that SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS CoV-2’s increased transmissibility.

Covid: Claims vaccinations harm fertility unfounded (BBC)

Claims on social media that the Covid vaccine could affect female fertility are unfounded, experts have said. Posts have incorrectly suggested the Pfizer vaccine could cause infertility in women, or cause their bodies to attack the placenta. But there is no "plausible biological mechanism" by which the vaccine could affect your fertility, says Prof Lucy Chappell, a professor in obstetrics at King's College London and spokesperson for the Royal College of Obstetricians and Gynaecologists...

Covid-19: World's first human trials given green light in UK (BBC)

Healthy, young volunteers will be infected with coronavirus to test vaccines and treatments in the world's first Covid-19 "human challenge" study, which will take place in the UK. The study, which has received ethics approval, will start in the next few weeks and recruit 90 people aged 18-30. They will be exposed to the virus in a safe and controlled environment while medics monitor their health. The UK has given doses of a Covid vaccine to more than 15 million people...

COVID-19 and the heart: What do we know so far?
Kimberly Drake | Feb 16, 2021

SARS-CoV-2, the virus that causes COVID-19, affects various organs and systems in the body, including the cardiovascular system. What do we currently know about its impact on the heart? This feature looks at the latest research and reveals what cardiologists have observed in the hospital setting.

...According to an article published in Science, of the family of seven human coronaviruses, scientists know that most affect the lungs but not the heart. SARS-CoV-2 is different because it may have a propensity to cause cardiac-related issues, such as inflammation of the heart, heart attack-like symptoms, and heart rhythm irregularities.

However, other, rather alarming data indicates that approximately 25% of people hospitalized with COVID-19 have cardiovascular complications, contributing to about 40% of all COVID-19-related deaths.

Interestingly, people with severe cases of the disease might not be the only individuals at risk for heart complications. Additional research published in JAMA Cardiology suggests that people who have had COVID-19 may experience cardiac involvement even with mild illness.

Even young adults may be at risk of COVID-19-related heart complications...15%...30%...

...at Cedars-Sinai, most of the patients who experience COVID-19-related heart complications are people who already have an underlying cardiac condition, such as heart failure or coronary disease... (on the up side, they have) not seen many new cardiac problems they could directly relate to COVID-19 disease.

...There are two main theories (how SARS-CoV-2 affects the heart)...Firstly, inflammation caused by the body’s robust immune response during COVID-19...can indirectly damage heart tissues by diminishing the heart’s blood supply and increasing the risk of heart inflammation...SARS-CoV-2 may cause heart tissue damage because of its distinct spike protein that can directly attach to and enter cardiac cells by binding with the heart’s angiotensin-converting enzyme 2 (ACE2) receptors.

...Areas of muscle cell death occurred in 35% of the 40 hearts examined. The scientists also found blood clots in the capillaries, or small blood vessels, in the heart tissue.

...At Cedars-Sinai, individuals admitted to the hospital with pre-diagnosed heart problems receive typical cardiac therapies in addition to medications for COVID-19...(ICU) treatment plans also incorporate anticoagulants

...(Cedars-Sinai's) Dr. (Johua) Goldhaber said, “it’s too early to tell, but (long-term heart problems) definitely something we’re worried about, given that there are patients who haven’t had pre-existing cardiac issues, who are complaining of exercise intolerance, and other symptoms that could be cardiac related.”

https://www.medicalnewstoday.com/articles/covid-19-and-the-heart-what-do-we-know...

Winter COVID-19: Climate less important than control measures
Timothy Huzar | February 12, 2021

...The researchers found that although the climate is likely to have some effect on the rate of SARS-CoV-2 transmission — it is far less significant a factor than control measures in the months leading up to winter, given the number of people who are still susceptible to the virus and how well the measures are implemented.

The researchers used New York as the basis for their modeling due to good access to past and current climate and COVID-19 data.

They found that the winter peak was most likely influenced by five factors. The first concerned the effectiveness and implementation of nonpharmaceutical interventions (NPIs) such as mask-wearing and social distancing.

The researchers estimated an effective NPI implementation of 35% but found that if this increased to 55%, these measures were better able to override climatic conditions.

The second and third factors concerned the duration of immunity and the accuracy of reporting. In the United States, only 10% of infections are currently being identified.

The final two factors concern how much the weather varies each year and how sensitive the virus is to climatic conditions such as humidity and heat. At present, researchers know that SARS-CoV-2 is more stable in cold, dry conditions.

...The researchers conclude that the virus is currently able to spread too quickly for the climate to play a significant role in reducing infections...But in the future, as the susceptibility of SARS-CoV-2 alters due to vaccination and natural immunity from infection, the role of control measures and climate is likely to become more finely balanced, they note.

https://www.medicalnewstoday.com/articles/winter-covid-19-climate-less-important...

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Rachel E. Baker et al. 2021. Assessing the influence of climate on wintertime SARS-CoV-2 outbreaks. Nature Communications volume 12, Article number: 846 (8 February 2021) https://www.nature.com/articles/s41467-021-20991-1

Abstract
High susceptibility has limited the role of climate in the SARS-CoV-2 pandemic to date. However, understanding a possible future effect of climate, as susceptibility declines and the northern-hemisphere winter approaches, is an important open question. Here we use an epidemiological model, constrained by observations, to assess the sensitivity of future SARS-CoV-2 disease trajectories to local climate conditions. We find this sensitivity depends on both the susceptibility of the population and the efficacy of non-pharmaceutical interventions (NPIs) in reducing transmission. Assuming high susceptibility, more stringent NPIs may be required to minimize outbreak risk in the winter months. Our results suggest that the strength of NPIs remain the greatest determinant of future pre-vaccination outbreak size. While we find a small role for meteorological forecasts in projecting outbreak severity, reducing uncertainty in epidemiological parameters will likely have a more substantial impact on generating accurate predictions.

...Discussion
Our results suggest that NPIs remain the primary determinant of future SARS-CoV-2 outbreak size. However, in a highly susceptible population, with NPIs in place that keep R0 just below 1, a small boost to transmission due to wintertime climate conditions could be sufficient to drive a large outbreak. In this case, more stringent NPIs may be required in winter months to limit such an outbreak. In all cases, if susceptibility is high, and NPI measures are reduced, large outbreaks will occur no matter the climate conditions.

There are several caveats to our results. First, the precise mechanism by which climate modulates seasonal transmission rates for viruses is currently unknown. ...

Second, we do not directly estimate the climate sensitivity of SARS-CoV-2. ...

Third, evidence from other respiratory viral pathogens implies that tropical locations may experience distinct climate drivers and dynamics of infection... Given our model is parameterized by fitting to US data, we may not have captured the full suite of possible climate drivers in these locations. While data from tropical climates are limited, evidence from Malaysia suggests persistent year-round infections for the endemic betacoronaviruses..., a feature our model is able to capture (Supplementary Fig. 9). However, possible secondary climate drivers will not be accounted for the model and could bias our results for tropical locations. We also note the US betacoronavirus data are at a course spatial resolution with a short time horizon, limiting our ability to identify the signal of interannual specific humidity variability on cases. A high correlation in the seasonality of specific humidity and temperature (Supplementary Fig. 10) limits our ability to separately identify the effect of these two variables. Fitting our model to temperature data would like give similar results.

Our results imply that meteorological and climate forecasts could be helpful in predicting future outbreak size (Supplementary Fig. 5). However, this information will likely be secondary to epidemiological monitoring such as estimates of the efficacy of active control measures in reducing transmission and serological surveys to determine susceptibility.... Titrating the impact of ongoing and future vaccination programs on susceptibility, and hence climate, will be important in the coming months. Current data from serological surveys suggest a minimal reduction in susceptibility in many locations..., with New York City towards the upper bound in terms of total reduction in susceptibility.... For many other locations, susceptibility may be much closer to 1, meaning the efficacy of NPIs will be a key determinant of winter outbreak size. While our model assumes a constant reduction in R0 due to NPIs, in reality policy makers likely adapt to rising case numbers by enforcing stricter measures. For instance, we estimated an R0 greater than 1 in Victoria, Australia in July and projected a much larger outbreak than has been observed to date (Supplementary Fig. 4). A second lockdown, enacted in Australia in August, substantially curbed this outbreak. Our results therefore suggest that more stringent NPIs may be required during the winter months to minimize total risk.

Eeew: Alien-like SARS-CoV-2 fuses with cell in nose. To the rescue: a nasal-spray lipopeptide designed to block fusion.
0:56 ( https://twitter.com/EricTopol/status/1362080258841710595 )
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Rory D. de Vries et al. 2021. Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science 17 Feb 2021:eabf4896 DOI: 10.1126/science.abf4896 https://science.sciencemag.org/content/early/2021/02/16/science.abf4896

Abstract

Containment of the COVID-19 pandemic requires reducing viral transmission. SARS-CoV-2 infection is initiated by membrane fusion between the viral and host cell membranes, mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection, and based on in vitro efficacy and in vivo biodistribution selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour co-housing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.

...The (SARSHRC-PEG4)2-chol peptide has a long shelf life, does not require refrigeration and can easily be administered, making it particularly suited to treating hard-to-reach populations. This is key in the context of COVID-19, which has reached every community with the burden falling disproportionately on low-income and otherwise marginalized communities. This HRC lipopeptide fusion inhibitor is feasible for advancement to human use and should readily translate into a safe and effective nasal spray or inhalation administered fusion inhibitor for SARS-CoV-2 prophylaxis, supporting containment of the ongoing COVID-19 pandemic.

Vin Gupta MD @VinGuptaMD | 10:07 PM · Feb 17, 2021:
As mentioned by @maddow tonight... please go to http://combatcovid.hhs.gov
if you’re covid +, have mild symptoms within the last ten days, are > 65 yrs or have preexisting conditions,
to learn more about eligibility for monoclonal antibodies

JOIN THE FIGHT
Find ways to prevent, treat or help fight COVID-19.
"If you have COVID-19 now, learn what your treatment options are or how to join a clinical trial."
https://combatcovid.hhs.gov/

----------------------------------------------------
(US MAP)
(Monoclonal Antibody) Therapeutics Distribution Locations

The national map below displays those locations that have received shipments of monoclonal antibody therapeutics under the U.S. Food and Drug Administration Emergency Use Authorization (EUA) authority, within the past several weeks. The monoclonal antibodies treatments Bamlanivimab (made by Eli Lilly and Company) and the therapeutic cocktail Casirivimab/Imdevimab (made by Regeneron) are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. Monoclonal antibodies treatments are given to help treat patients with COVID-19.

IMPORTANT: This data is based on shipments reported by the distributor, and is not a guarantee of availability. Patients should coordinate with their respective physician or care provider before contacting a location to receive treatment. Locations that received fewer than 5 courses of treatment are not displayed. These therapeutics must be used under the terms of the EUA for appropriate patients. Data displayed on this page is for informational purposes only for clinicians and patients.

https://protect-public.hhs.gov/pages/therapeutics-distribution

The place to start, I think, is with African health workers. They need the very best protection and can hopefully navigate any needed cold chain, monoclonal antibody infusion. Then flood populations with one-jab, less demanding vaccines (J&J? Astrazeneca? Russian & Chinese?) and therapeutics. At that point, hopefully, more vaccines and boosters for new strains will be available, and new plans can be made.

May be different in UK, but in my corner of US, roll-out is very chaotic. I have appointment (as an over-65) at pharmacy March 4, but already the store has been cancelling for lack of supplies, so I'm not optimistic.

In my summer corner of Ontario, with lower supply, frontline HCW have been vaxxed as well as 70% of longterm care residents, who were already most at risk, before B117 arrived. 80YO are next in line when/if vaxx doses arrive from Belgium. https://www.nytimes.com/2021/02/18/world/canada/canada-vaccine-coronavirus.html

Unprotected African health workers die as rich countries buy up COVID-19 vaccines
Kai Kupferschmidt | Feb. 17, 2021

...Global inequities have existed since the start of the COVID-19 pandemic. ICUs, ventilators, and oxygen are scarce throughout the African continent, for instance. But in the early months, the basic public health measures required to control spread of the virus put countries more or less on an equal footing, says John Nkengasong, head of the Africa Centres for Disease Control and Prevention. And Africa has weathered the pandemic relatively well, in part because of its young population.

But now, the rollout of vaccines has put rich countries at a definitive advantage...

https://www.sciencemag.org/news/2021/02/unprotected-african-health-workers-die-r...

Boris Johnson to pledge surplus Covid vaccine to poorer countries at G7 (Guardian)

Both Russia and China are threatening to win an escalating vaccine diplomacy war by sending their vaccines direct to Africa, while the G7 club of wealthy nations continues to pile up surplus supplies as insurance against stocks running out...

Which really says it all. Poorer countries are only entitled to what is "surplus" to the requirements of rich countries, not an equal share of a lifesaving vaccine.

Covid vaccines: Macron proposes sending 4-5% of doses to poorer nations (BBC)

Hm. 4-5% of the vaccines for approximately 75% of the world's population. Very generous.

World's poor need action, not Covid 'vaccine nationalism', say experts (Guardian)

if the issue of vaccine distribution is not resolved, it will result in years of resentment between rich and poor nations... the world was on the “brink of a catastrophic moral failure”...

White House announces $4 billion in funding for Covax, the global vaccine effort that Trump spurned
Emily Rauhala, Erin Cunningham and Adam Taylor | Feb. 18, 2021

The White House is throwing its support behind a global push to distribute coronavirus vaccines equitably, pledging $4 billion to a multilateral effort the Trump administration spurned.

At a Group of Seven meeting of leaders of the world’s largest economies Friday, President Biden will announce an initial $2 billion in funding for Gavi, the Vaccine Alliance, to be used by the Covax Facility, senior administration officials said in a briefing.

The United States will release an additional $2 billion over two years once other donors have made good on their pledges and will use this week’s G-7 summit to rally other countries to do more.

The money, which was appropriated by a bipartisan congressional vote last year, will give a much needed boost to a program jointly led by Gavi, the World Health Organization and the Coalition for Epidemic Preparedness Innovations...

https://www.washingtonpost.com/world/2021/02/18/5-percent-vaccine-donations-fran...

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U.S. and Novavax Will Aid Global Vaccination Campaign
Sheryl Gay Stolberg | Feb. 18, 2021

...the pharmaceutical company Novavax committed to sell 1.1 billion doses of its vaccine. ( https://www.nytimes.com/2021/02/03/health/vaccine-novavax.html )

...So far, the United States has pledged more than any other nation, according to the White House; the official said the goal was to leverage the second tranche of $2 billion into as much as $15 billion — the amount the administration believes is necessary to increase the supply of vaccine around the world and to distribute it.

Those leading the Covax effort greeted the Novavax announcement with enthusiasm. Dr. Seth Berkley, the chief executive of Gavi, said in a statement that the donation would help the campaign “close in on our goal of delivering two billion doses in 2021.” He said it would also expand the range of vaccines it could rely on to “build a portfolio suitable for all settings and contexts.”

https://www.nytimes.com/2021/02/18/us/politics/biden-novavax-covax-vaccinations....

______________________________________________________

"In 2003, the U.S. government launched the President’s Emergency Plan for AIDS Relief (PEPFAR): the largest commitment ever by any nation to address a single disease. Fifteen years later, PEPFAR has saved millions of lives, prevented millions of new infections, and changed the course of the epidemic." https://www.cdc.gov/globalhivtb/who-we-are/pepfar15/PEPFAR15.html

"The development of an effective Ebola vaccine by Canada’s National Microbiology Laboratory is a great Canadian contribution to global public health." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662448/

Brief thread to debunk the repeated claims we hear about transmission not happening 'within school walls', infection in school children being 'a reflection of infection from the community', and 'primary school children less likely to get infected and contribute to transmission'...
- Deepti Gurdasani | Feb 18, 2021
https://threadreaderapp.com/thread/1362390053029306368.html

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from

Deepti Gurdasani* @dgurdasani1 | 8:14 AM · Feb 18, 2021:

Brief thread to debunk the repeated claims we hear about transmission not happening 'within school walls', infection in school children being 'a reflection of infection from the community', and 'primary school children less likely to get infected and contribute to transmission'...

https://twitter.com/dgurdasani1/status/1362390053029306368

* Deepti Gurdasani @dgurdasani1
Senior Lecturer @QMUL ( Queen Mary University of London )
Epidemiology, statistical genetics, machine learning.
Intersectional feminist. Advocating for a better culture in academia. All views mine.

_____________________________________________________
Denmark

Kolding school outbreak does not bode well for March 1 partial reopening, warn experts
Ben Hamilton | February 19th, 2021

Speed of infections underline the devastating potential of the British mutation and raise questions as to how vulnerable children might be to contracting this particular variant

...Something weird with the kids
Speaking to DR, Viggo Andreasen, an associate professor at Roskilde University who is swiftly becoming the nation’s favourite mathematical epidemiologist, questions whether there is “something going on with the infection of (the British variant) B117 among children that we have not seen with the old coronavirus...If we see more examples like this, then we must ask ourselves whether it is too risky to open the schools to the little ones...This means there is a good risk that infection chains will run for quite some time before we discover them. There are probably also some parents who have become infected.”...

https://cphpost.dk/?p=122479

Good news on Pfizer-BioNTech vaccine: one dose efficacy and storage requirements

ETA:
Pfizer/BioNTech first dose 85% effective after 2-4 weeks: study
February 19, 2021
https://medicalxpress.com/news/2021-02-pfizer-dose-effective-weeks.html

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Sharon Amit et al. 2021. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 (Pfizer/BioNTech) vaccine recipients. The Lancet ( February 18, 2021) DOI:https://doi.org/10.1016/S0140-6736(21)00448-7 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00448-7/fullt... https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900448-7

...Adjusted rate reductions of SARS-CoV-2 infections were 30%... and 75% ... for days 1–14 and days 15–28 after the first dose, respectively...

...Adjusted rate reductions of COVID-19 disease were 47% ... and 85% ... for days 1–14 and days 15–28 after the first dose, respectively.

Our data show substantial early reductions in SARS-CoV-2 infection and symptomatic COVID-19 rates following first vaccine dose administration. Early reductions of COVID-19 rates provide support of delaying the second dose in countries facing vaccine shortages and scarce resources, so as to allow higher population coverage with a single dose. Longer follow-up to assess long-term effectiveness of a single dose is needed to inform a second dose delay policy.

_____________________________________________________________________

Pfizer says deep-freeze storage unnecessary as Israeli study shows vaccine 85% effective after 1st shot
CBS/AFP | February 19, 2021

...Pfizer says deep-freeze unnecessary

Pfizer and BioNTech announced their submission of research data on storage temperatures to the FDA in a joint statement on Friday. ( https://biontechse.gcs-web.com/news-releases/news-release-details/pfizer-and-bio... )

The FDA's Emergency Use Authorization for the vaccine, issued months ago, stipulates that it be stored at temperatures well below zero (-112ºF to ‑76ºF), which requires special equipment for both transport and storage at health care facilities. Under the companies' new recommendation, the vaccine could be stored for up to two weeks at standard freezer temperatures of -13°F to 5°F, "as an alternative or complement to storage in an ultra-low temperature freezer."

"We have been continuously performing stability studies to support the production of the vaccine at commercial scale, with the goal of making the vaccine as accessible as possible for healthcare providers and people across the U.S. and around the world," Pfizer CEO Albert Bourla said in the Friday statement announcing the request to the FDA to change its guidance. "We appreciate our ongoing collaboration with the FDA and CDC as we work to ensure our vaccine can be shipped and stored under increasingly flexible conditions. If approved, this new storage option would offer pharmacies and vaccination centers greater flexibility in how they manage their vaccine supply."

"The data submitted may facilitate the handling of our vaccine in pharmacies and provide vaccination centers an even greater flexibility," added BioNTech CEO and Co-founder Ugur Sahin. "We will continue to leverage our expertise to develop potential new formulations that could make our vaccine even easier to transport and use."

https://www.cbsnews.com/news/pfizer-vaccine-covid-one-dose-deep-freeze-not-neces...

Oxford Astrazeneca vaccine:

Merryn Voysey et al. 2021. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. The Lancet (February 19, 2021) DOI:https://doi.org/10.1016/S0140-6736(21)00432-3 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fullt...

...A 3-month dose interval (between 1st and 2nd doses) might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose...

Can a heart failure drug help treat long COVID symptoms?
James Kingsland | February 18, 2021

Some people who have recovered from COVID-19 experience ongoing symptoms — such as brain fog, increased heart rate, and chronic fatigue — sometimes known as long COVID.

There is an overlap between the symptoms of long COVID and postural orthostatic tachycardia syndrome (POTS), which has led some researchers to suggest they are related (COVID may trigger). ( rapid heart rate of more than 100 beats per minute — when a person stands up, poor concentration or brain fog, lightheadedness, dizziness or fainting, blurred vision, palpitations, nausea, tiredness )

A small clinical trial suggests that ivabradine, a drug approved for use in heart failure, may be an effective treatment for POTS, with fewer side effects than existing treatments...

https://www.medicalnewstoday.com/articles/can-a-heart-failure-drug-help-treat-lo...

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Satish R. Raj, Robert S. Sheldon. 2021. Higher Quality Evidence to Guide Our Management of Postural Orthostatic Tachycardia Syndrome. Journal of the American College of Cardiology, Volume 77, Issue 7, 23 February 2021, Pages 872-874
https://www.sciencedirect.com/science/article/abs/pii/S0735109720381316

Abstract
...Conclusion
Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.

Biden administration, vaccine makers scramble to outflank coronavirus variants
Laurie McGinley and Christopher Rowland | Feb. 19, 2021

...Drug companies already have started working on updating their vaccines against new, more transmissible variants — a move encouraged by government officials.

“What we are saying is, ‘Go ahead and study them, get them ready to go,” said a health official who spoke on the condition of anonymity to discuss the message conveyed to manufacturers. “You do a construct for the 351 variant first detected in South Africa, test it in people and get all the information. If you need it a few months from now, you have it. You essentially hold them in the freezer” until needed.

While the current shots by Pfizer-BioNTech and Moderna use a new technology that allows for speedy modifications, changing vaccines adds wrinkles to manufacturing and distribution schemes that are already complex.

...Both (Pfizer-BioNTech and Moderna) are preparing to test new versions of their vaccines in small clinical trials, something they have framed as a precautionary step. Pfizer said this week it is studying the potential for a revised vaccine that would target original and new strains of the virus, as well as a stand-alone booster aimed at the South Africa variant and possibly others. It also plans to test how effective a third shot of the current two-dose vaccine would be at quelling infection by the variants if given at either six or 12 months. Moderna said late last month it plans to test an additional booster to its original vaccine and another one targeting the B. 1.351 variant.

A prime inventor of the technology behind mRNA vaccines, Drew Weissman, of the University of Pennsylvania, said he has been told by the leader of BioNTech that it could take as little as six weeks to formulate a new mRNA payload and manufacture it to target a variant. Pfizer chief executive Albert Bourla told investors earlier this month that he anticipates that a variant-specific vaccine could be approved in 100 days, including clinical testing and regulatory reviews.

The best approach to creating new shots would be to pack multiple mRNA strands tailored for various mutations into a single shot...But the drug companies first have to create an effective vaccine against a single variant, to be able to test it in isolation, before it can be combined...

The next vaccine likely to get emergency authorization from the FDA — Johnson & Johnson’s — was shown to be 57 percent effective against moderate and severe covid-19 in its late-stage clinical trial in South Africa, where B. 1.351 is prevalent. The results were even more impressive against severe disease — the company said the vaccine was 89 percent effective in South Africa in preventing hospitalizations and deaths.

...South Africa said this month it was suspending the rollout of AstraZeneca’s vaccine after researchers found that it provided “minimal protection” against mild-to-moderate coronavirus infections there after the variant became prevalent. Whether it protects against severe disease remains unknown, according to the researchers. Sarah Gilbert, a professor of vaccinology at the University of Oxford who conducted the initial research on the AstraZeneca vaccine, said in a statement that “efforts are underway to develop a new generation of vaccines that will allow protection to be redirected to emerging variants as booster jabs, if it turns out that it is necessary to do so.”

Novavax, another company that has received U.S. government support to develop a vaccine, is conducting a late-stage clinical trial in the United States of its original vaccine candidate, while also developing a version against the South African variant. It said in January that its original vaccine showed diminished effect against the variant in lab dishes but was still protective...

https://www.washingtonpost.com/health/2021/02/19/vaccine-updates-coronavirus-var...

Half the previously infected whose blood South Africa tested against its new variant had lost all neutralizing activity...

National Institute for Communicable Diseases (South Africa)
18 January 2021

Can you be re-infected with the new variant if you have already had COVID-19 from one of the older variants?

People who have recovered from SARS-CoV-2 infection are usually protected from being infected a second time (called re-infection). This is because they develop neutralizing antibodies that remain in their blood for at least 5-6 months, maybe longer. These antibodies bind to specific parts of the spike protein that have mutated in the new variant (K417N and E484K). We now know that these mutations have allowed the virus to become resistant to antibody neutralization.

The blood samples from half the people we tested showed that all neutralizing activity was lost. This suggests that they may no longer be protected from re-infection. In the other half, the levels of antibodies were reduced and so the risk of re-infection is not known. It is therefore important that people who have previously had COVID-19 continue to adhere to public health measures. Protecting ourselves through masks, regular washing or sanitising of hands, cleaning of surfaces, and social distancing remain the best defense against all SARS-CoV-2 viruses, including the new lineage.

https://www.nicd.ac.za/can-i-be-re-infected-with-the-new-variant-if-ive-had-covi...

G7 pledges extra $7bn towards Covid vaccines for world's poorest (Guardian)

UN secretary general calls for new global emergency plan to ensure vaccines distributed equitably...

GOOD NEWS for making supplies go further if one's robust rxn to first dose of mRNA vaccine means a 2nd will not be needed. Sounds, too, like those previously affected by original strain, can after one dose mRNA vaccine "neutralize not only B.1.351, but also the coronavirus that caused the SARS epidemic in 2003."

Eric Topol (physician-scientist) @EricTopol | 2:56 PM · Feb 9, 2021:
How many studies are needed before we accept that
people with prior covid-19 have a robust immune Ab response to a single dose of mRNA vaccines,
like the 2nd dose for those with no prior covid?

https://medrxiv.org/content/10.1101/2021.01.30.21250843v2.full.pdf
https://medrxiv.org/content/10.1101/2021.01.29.21250653v1
https://medrxiv.org/content/10.1101/2021.02.05.21251182v1.full.pdf

Image-graphs from 3 preprints above ( https://twitter.com/EricTopol/status/1359229698669113344/photo/1 )

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Eric Topol @EricTopol | 9:45 AM · Feb 20, 2021:
And then there were four

https://medrxiv.org/content/10.1101/2021.02.07.21251311v1
Image--graphs ( https://twitter.com/EricTopol/status/1363137622961319944/photo/1)

https://nytimes.com/2021/02/19/health/covid-vaccine-single-dose.html *
Image-NYT article w/ highlights ( https://twitter.com/EricTopol/status/1363137622961319944/photo/2 )

________________________________________________________

* People Who Have Had Covid Should Get Single Vaccine Dose, Studies Suggest
New studies show that one shot of a vaccine can greatly amplify antibody levels in those who have recovered from the coronavirus.
Apoorva Mandavilli | Feb. 19, 2021

...people who have had Covid-19 should be immunized — but a single dose of the vaccine may be enough.

A person’s immune response to a natural infection is highly variable. Most people make copious amounts of antibodies that persist for many months. But some people who had mild symptoms or no symptoms of Covid-19 produce few antibodies, which quickly fall to undetectable levels...anyone who has recovered from Covid-19 produces enough antibodies to protect against the virus.

...one shot of either the Pfizer-BioNTech or Moderna vaccine significantly changed the picture: It amplified the amount of antibodies in their blood by a thousandfold...Flush with antibodies, samples from all of the participants could neutralize not only B.1.351, but also the coronavirus that caused the SARS epidemic in 2003.

In fact, the antibodies seemed to perform better than those in people who had not had Covid and had received two doses of a vaccine. Multiple studies have suggested that the Pfizer-BioNTech and Moderna vaccines are about five times less effective against the variant.

...The researchers don’t yet know how long the increased amount of antibodies will persist...The researchers also saw increases in immune cells that remember and fight the virus

In another new study...a second dose of the vaccine did not add much benefit at all for people who have had Covid-19 — a phenomenon that has also been observed with vaccines for other viruses.

It’s unclear whether the thousandfold spike in antibody levels recorded in the lab will occur in real-life settings...Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York...showed that people who have had Covid-19 and received one dose of a vaccine experienced more severe side effects from the inoculation and had more antibodies compared with those who had not been infected before.

“If you put all four papers together, that’s providing pretty good information about people who already had an infection only needing one vaccination,” Dr. Krammer said.

The fact that the supercharged antibodies observed in the new study can fight the 2003 SARS virus suggests that a single dose of the vaccine may have prompted the volunteers’ bodies to produce “broadly neutralizing antibodies” — immune molecules capable of attacking a broad range of related viruses, Dr. Burton said.

...The new study may provide clues on how to make a single vaccine that stimulates the production of broadly neutralizing antibodies that can destroy all variants of the coronavirus, (Dennis R. Burton, an immunologist at the Scripps Research Institute in La Jolla, Calif.) said...Without such a vaccine, scientists will need to tweak the vaccines every time the virus changes significantly. “You’re stuck in a kind of Whac-a-Mole approach,” he said. It will probably take many months if not longer to develop and test that sort of vaccine against the coronavirus, but “that’s the longer-term way to approach this virus.”

https://www.nytimes.com/2021/02/19/health/covid-vaccine-single-dose.html

GRAPH: Daily new COVID cases per million people, rolling 7-day average, by continent (Mar 11, 2020 - Feb 19, 2021)
OUR WORLD IN DATA via Eric Topol:

https://twitter.com/EricTopol/status/1363141659349852167/photo/1

Dunno about COVID-19, but sucking on Zn lozenges when I have a sore throat appear to eliminate or greatly reduce course of a cold--and I used to have whoppers! Sounds like Zn was given in one oral dose, and after PCR test, so not early. Methinks the editorial overstated their case against supplements based on the cited study, thus misusing science in their animuz against supplements. IMHO, anyway.

Erin D. Michos and Miguel Cainzos-Achirica. 2021. Supplements for the Treatment of Mild COVID-19—Challenging Health Beliefs With Science From A to Z. JAMA Netw Open. Feb 12, 2021;4(2):e210431. doi:10.1001/jamanetworkopen.2021.0431

“The good thing about science is that it’s true whether or not you believe in it.”
Neil deGrasse Tyson

Coronavirus disease 2019 (COVID-19) is a major cause of death and disability worldwide, totaling 89.4 million cases and 1.9 million deaths globally as of January 9, 2021. As a result of high-quality science, several vaccines efficacious against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed in record time and deployment started, offering hope for an end to the pandemic. However, given the limited availability and uptake of vaccines, the emergence of new, more infectious variant strains of the virus, and the potential for future seasonal outbreaks, the identification of therapies that can effectively improve prognosis in patients infected with SARS-CoV-2 remains a critical area of research.

Commonly available oral supplements, such as zinc and ascorbic acid (ie, vitamin C), have been proposed to reduce the duration and severity of viral infections by boosting immune response. Even former US President Donald Trump was reportedly treated with zinc and vitamin D throughout his COVID-19 treatment in October 2020. Although the evidence supporting supplements as a treatment for viral infections is rather limited, in a context of rapidly increasing COVID-19 deaths and urgent need for effective therapeutic options, whether these molecules could benefit patients with COVID-19 is a research question worth evaluating.

Thomas et al report the results of the COVID A to Z Study, an open-label, 4-group, randomized clinical trial (RCT) that tested the efficacy of high-dose zinc gluconate, ascorbic acid, and their combination for their ability to shorten the duration of COVID-19–related symptoms compared with usual care alone. The authors planned to include 520 adult outpatients with confirmed SARS-CoV-2 infection, and the primary end point was the number of days required to reach a 50% reduction in symptom severity. However, after an interim analysis, the safety monitoring board recommended the study be stopped early for futility after enrollment of only 214 participants because of the low probability of detecting significant differences between the study groups in terms of the primary end point.

Some limitations of the study by Thomas et al are worth discussing. First, enrollment was restricted to outpatients, thus limiting generalizability to hospitalized patients with COVID-19. Second, interventions were not blinded, a placebo was not used in the control group, and outcomes were reported by study participants. This could have exaggerated the potential benefit of the interventions; yet, the study yielded null findings, providing further reassurance that the early trial termination did not conceal detection of a true benefit. Finally, the small size prevented conducting subgroup analyses by relevant clinical characteristics, although those would have to be interpreted cautiously in the context of overall null findings.

The supplement industry is estimated to be worth approximately $300 billion globally.6 More than one-half of US adults report taking at least 1 vitamin or supplement for various health reasons, with little evidence of efficacy to support their widespread use. The best evidence to guide clinical recommendations comes from well-designed RCTs. Given the widespread public use of supplements, such as zinc and ascorbic acid, for the prevention and treatment of viral infections, we applaud the COVID A to Z Study investigators for adding rigorous science by testing their efficacy and challenging popular beliefs. Unfortunately, these 2 supplements failed to live up to their hype.

There is frequently disconnect between mechanistic and/or observational research and the eventual findings from well-conducted RCTs. Specifically, research on the health effects of both supplements and therapies for COVID-19 has been rich in examples of this disconnect. Low vitamin D levels have been associated with multiple adverse health outcomes, including cardiovascular disease, in several observational studies, and the mechanistic rationale for increasing vitamin D levels seemed compelling. However, subsequent RCTs of vitamin D supplementation consistently yielded null results for cardiovascular disease, even among individuals with low baseline levels. The previously reported associations of vitamin D and cardiovascular outcomes were likely driven by confounding from other risk and health factors. The same had been true for multiple other vitamins and mineral supplements, with discordance between observational and trial evidence. It is likely that other health-seeking behaviors characteristic of supplement users confounded the observational studies. Enthusiasm for other COVID-19 treatments has been similarly dampened after completion of RCTs. Hydroxychloroquine, an antimalarial drug widely repurposed as drug candidate for COVID-19 prevention and treatment, also failed to demonstrate efficacy in RCTs.

What are the implications, moving forward, of yet another null COVID-19 trial?5 Given current projections that in coming weeks the pandemic will continue to peak worldwide, together with the potential for future outbreaks, this new disappointment should not discourage further research efforts. Those will be critical to eventually identifying truly efficacious therapeutic options to help reduce the burden of death and other severe complications. The groundbreaking developments in antiviral therapeutics against a foe as challenging as HIV provide strong, evidence-based reasons for hope in science and human discovery.

Despite the urgency, we suggest that some pause may be needed moving forward. Although supplements are generally thought of as benign because of their over-the-counter availability, they are not necessarily free from adverse effects. Indeed, in the COVID A to Z Study, 5 more adverse effects (nausea, diarrhea, and stomach cramps) were reported in the supplement groups than in the usual care group. Safety has also been a concern with other COVID-19 candidate therapies. For instance, in the recently published phase 3 hydroxychloroquine trial (BCN-PEP-CoV2),8 which tested prophylactic use among contacts of patients with confirmed COVID-19, a striking 56% of participants in the hydroxychloroquine group developed adverse effects compared with only 6% in the control group, with 5-fold increases in moderate and severe adverse effects with hydroxychloroquine. Solid phase 1 and 2 data should be generated before drugs with potential to cause harm are administered to large study populations in phase 3 trials. In a context of limited resources for costly experimental research, funding agencies could prioritize candidate interventions on the basis of their safety and favor those with the strongest body of preliminary evidence.

Finally, although studies on the efficacy of pharmacotherapies for COVID-19 are certainly needed and this has been an active area of research since the start of the pandemic, in stark contrast, there has been a lack of experimental research on policy and social interventions. Multiple observational studies have identified adverse socioeconomic circumstances and limited access to care as powerful factors associated with adverse COVID-19 outcomes in the US, with a disproportionate impact on historically marginalized groups. This was echoed by a report from the Centers for Disease Control and Prevention, and yet, large studies evaluating related interventions have remained scarce. For instance, we need to better understand how to increase access to risk-mitigation measures and testing among those most often exposed to SARS-CoV-2 infection, typically essential workers of socioeconomically vulnerable groups. Beyond molecules and drugs, the time may have come for funding agencies to boost research on more upstream interventions, and, if they are proven effective, for the US Congress to invest in their implementation.

In recent years, misinformation has permeated health discussions, including those involving COVID-19 therapies. The Biden-Harris administration has expressed a will to embrace science, and we hope that 2021 will start an era in which high-quality research will inform political and public health decision-making, an era in which scientists, public health officials, and government can be invested together in addressing key research gaps, generating and disseminating highest-quality information, and tackling key unmet social needs of the country—during and beyond the pandemic.

_________________________________________________

Suma Thomas et al. 2021. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. February 12, 2021;4(2):e210369. doi:10.1001/jamanetworkopen.2021.0369 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305?

Key Points
Question Do high-dose zinc, high-dose ascorbic acid, and/or a combination of the 2 reduce the duration of symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

Findings In this randomized clinical trial of 214 patients with confirmed SARS-CoV-2 infection receiving outpatient care, there was no significant difference in the duration of symptoms among the 4 groups.

Meaning These findings suggest that treatment with zinc, ascorbic acid, or both does not affect SARS-CoV-2 symptoms.

Abstract
Importance There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression.

Objective To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection.

Design, Setting, and Participants This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020.

Intervention Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care.

Outcomes The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements.

Results A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups.

Conclusions and Relevance In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care.

Covid-19: Which countries in Africa are administering vaccines? (BBC)

Africa has now recorded more than 100,000 deaths from coronavirus, and there's been concern over the delay in rolling out Covid-19 vaccinations there. We've looked at what's been happening with vaccinations on the continent...

"It is deeply unjust that the most vulnerable Africans are forced to wait for vaccines while lower-risk groups in rich countries are made safe"...

>27 margd: Spanish preprint "Calcifediol Treatment and COVID-19-Related Outcomes" has been removed, and Lancet is conducting an investigation. The public probably won't hear more, unless another version emerges somewhere? I've seen preprints suffer untimely demise before, but usually because mossbacks found some obvious limits in study design or conclusions drawn.

According to Wikipedia, the first authors' institute sounds like a solid one: "UAB (Autonomous University of Barcelona) is the second best university in Spain, after the University of Barcelona, located in the same city, according to the 2020 QS World University Rankings, which ranked the university 176th overall in the world."

Dear Preprints with the Lancet Readers,

We have removed this preprint due to concerns about the description of the research in this paper. This has led us to initiate an investigation into this study.

The comments that have been posted on this preprint will remain available on this page. Please note that this comment thread is now closed to further posts.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3771318

Kai Wu et al. 2021. Serum Neutralizing Activity Elicited by (Moderna) mRNA-1273 Vaccine — Preliminary Report (Letter). NEJM February 17, 2021. DOI: 10.1056/NEJMc2102179 https://www.nejm.org/doi/full/10.1056/NEJMc2102179

...We assayed the serum neutralizing activity against recombinant vesicular stomatitis virus (rVSV)–based SARS-CoV-2 (a pseudovirus-based model) ...bearing the spike protein from
the original Wuhan-Hu-1 isolate,
the D614G variant,
the B.1.1.7 (UK) and
B.1.351 (S Africa) variants, and
other variants (20E EU1, 20A.EU2, N439K-D614G, and the mink cluster 5 variant that was first identified in Denmark).

...no significant effect on neutralization by serum obtained from participants who had received the mRNA-1273 vaccine in the phase 1 trial (Wuhan and related vatiant?)

...In contrast, we observed a decrease in titers of neutralizing antibodies against the B.1.351 variant and a subset of its mutations affecting the RBD--reductions by a factor of 2.7 in titers of neutralizing antibodies against the partial panel of mutations and by a factor of 6.4 against the full panel of mutations...

However,...the geometric mean neutralizing titer against B.1.351 was 1:290, and all the serum samples neutralized the rVSV pseudovirus, albeit at relatively low dilutions... ( Protection against the B.1.351 variant conferred by the mRNA-1273 vaccine remains to be determined. )

...We observed levels of neutralization against these (against the full-length spike protein of the dominant strain in 2020 (D614G), as well as against 20E (EU1), 20A.EU2, N439K-D614G, and mink cluster 5 variants ) that were similar to those against the Wuhan-Hu-1 (D614) isolate...

S Africa cases down to pre-B.1.351 levels!

Eric Topol (physician scientist) @EricTopol | 1:11 PM · Feb 21, 2021:
The good news is that South Africa is back to its pre-B.1.351 baseline in covid cases.
There's no proof this variant is more infectious.
Its immune evasion is enough to explain how it took off. And the descent occurred without vaccines.
Image-S African cases Mar 2020-Feb 2021 ( https://twitter.com/EricTopol/status/1363551912021221377/photo/1 )

Nate Silver @NateSilver538 | 1:21 PM · Feb 21, 2021:
We know that B.1.351 causes some immune escape...
but in your view does the rapid decline in cases in South Africa mean
we should revise priors on just how much it has?

Eric Topol @EricTopol | 1:30 PM · Feb 21, 2021:
Great question, w/ data so mixed:
The failure of the Astra Zeneca vaccine to prevent mild-moderate infections
The preserved, albeit reduced efficacy (cf ancestral) of Novavax (96->60 margd:) and J&J (72->57 margd:)
The reinfections are concerning
But perhaps not as bad as we've been thinking

Zoë McLaren, PhD @ZoeMcLaren | 1:31 PM · Feb 21, 2021:
Transmissibility is always relative to set of policies/behaviors in place.
This data means that we can control the spread of this variant with the tools we have.
Even if it is more infectious in certain contexts.
Let’s take our concerns about variants down a notch.

Simulation of herd immunity via vaccination rates and previously infected.
Very simple model, but looks like masks, etc., might help and will be warranted for a while yet?

How Herd Immunity Works — And What Stands In Its Way
Thomas Wilburn Richard Harris | February 18, 2021

What will it take to finally halt the spread of the coronavirus in the U.S.? To answer that question we've created a simulation of a mock disease we're calling SIMVID-19.

When you click "Run Simulation"...you are witnessing how a disease can spread through a population and how increased levels of vaccination can stop it in its tracks...

1) A more infectious variant takes over...
2) A population is already heavily exposed...
3) A population has low levels of initial immunity...

Takeaways for COVID-19
In our SIMVID-19 scenarios, 75% vaccination rates were able to kick the imaginary disease in all but one scenario, the more infectious variant. For the U.S. to tame its coronavirus outbreak through herd immunity, scientists expect that somewhere between 70% and 85% of the population must be immune.

...One thing that's evident from this simulation (and real life) is that the faster the population is protected by vaccination the better.

https://www.npr.org/sections/health-shots/2021/02/18/967462483/how-herd-immunity...

Share of people who have received at least one dose vaccines, Feb 21, 2021. By country. (Bar graph):
https://twitter.com/DrEricDing/status/1363801146872193025/photo/1

Canada, not on bar graph:
The cumulative percent of the population who have received at least one dose of a COVID-19 vaccine in Canada was 2.56%, as of February 13, 2021. ( https://health-infobase.canada.ca/covid-19/vaccination-coverage/ )

Dr. Richard Corsi (engineering dean U TX) @CorsIAQ | 1:15 AM · Feb 22, 2021
https://twitter.com/CorsIAQ/status/1363734149182332937
#1 of 8 tweets: One of my slides. Cost of good portable HEPA filter system in a 600 to 800 square ft classroom with 25 students (equivalent ACH increase of 2.7 to 3.5/h). Cost is broken down by classroom and student.
Image ( https://twitter.com/CorsIAQ/status/1363734149182332937/photo/1 )
...

or

https://threadreaderapp.com/thread/1363734149182332937.html

ETA: the end of the holiday effect?

Dr. Tom Frieden (FRMR CDC director) @DrTomFrieden | https://twitter.com/DrTomFrieden/status/1363862952902856708
Yes, immunity likely playing a role in rapidity of case decrease.
But more than twice as many people have immunity from infection as from vaccination and most people still susceptible.
Masks, movement and reductions in shared indoor air drive the decrease.

Image-spent time w others graph, Oct 2020 to mid Feb 2021
( https://twitter.com/DrTomFrieden/status/1363862952902856708 )

Blog: Covid Epidemiology
Dr. Tom Frieden | 2-20-21

(1) Safer Doesn’t Mean Safe (Yet)

(2) Variants Are the Wild Card

(3) Death and Vaxes
Although vaccination has not yet had a major effect on Covid cases overall, it IS driving down nursing home deaths: the share of deaths associated with long-term care facilities has been cut in HALF since early January, from more than 30% as a proportion of all deaths from Covid to less than 20%.

With most nursing home residents and many other people over age 65 having been vaccinated, I will make a prediction: the infection fatality ratio will likely drop from the current 1 in 200 infections resulting in death to less than 1 in 600 by some time in March...

https://www.tomfriedenpublichealth.net/tom-frieden-blog#safer-doesnt-mean-safe-y...

https://bit.ly/37zWDcE

COVID-19 vaccine could cause mammogram result confusion, doctors say
Elaina Athans | February 23, 2021 2:10AM

Doctors are seeing several women coming in for mammograms with the same issue and it's causing concern. The patients have swollen lymph nodes, which is a rare sign of breast cancer.

"When we see that, we perk up and get worried," said Dr. Lars Grimm of Duke Health.

...Lymph nodes will be swollen on the side of the body the person received the (mRNA COVID) shot.

The side effect, though, is that those lumps will show up a mammogram and give a false reading for breast cancer.

Grimm says women just need to do some planning. Either get the mammogram screening done before the first COVID-19 vaccine dose, or four to six weeks after the second shot.

Grimm says the recommended timetable is the same whether you're getting the Moderna or Pzifer vaccine...

https://abc13.com/covid-vaccine-mammogram-breast-cancer-immune-response/10362072...

Does the Vaccine Stop Transmission?
How to understand the difference between vaccination to prevent Covid-19 and shots to halt infection.
Angela L. Rasmussen* | Feb. 23, 2021

...Will being vaccinated stop the spread of Covid-19 so they can socialize outside their bubbles and dine indoors with abandon?
Eventually, yes.

...When scientists develop a vaccine against a novel virus, it’s difficult to predict whether vaccination will completely prevent infection — what’s called sterilizing immunity. If the Covid-19 vaccines do not provide sterilizing immunity, it means a vaccinated person can still inhale enough of the SARS-CoV-2 virus to develop an infection, and it will be swiftly cleared from the body before becoming Covid-19, but that person could still pass the infection to another person.

There are many vaccines that do not provide fully sterilizing immunity but nonetheless have huge public health benefits. Every year, the flu vaccine saves lives and keeps people out of the hospital despite the fact that it doesn’t prevent infection altogether. ( Historical evidence shows that vaccines that do not prevent virus infection can still stop epidemics in their tracks. The polio vaccine developed by Dr. Jonas Salk, which does not provide sterilizing immunity, resulted in the rapid elimination of polio in the United States beginning in the 1950s. )

From everything we know so far, it’s highly unlikely that vaccines that are 95 percent effective at preventing symptomatic disease would have no impact whatsoever on infection.

*Dr. Rasmussen is a virologist at the Center for Global Health Science and Security at Georgetown University Medical Center. She studies the host response to infection with emerging viruses, including the coronavirus.

https://www.nytimes.com/2021/02/23/opinion/covid-vaccines-transmission.html

...The researchers discovered a correlation between a surge in (Google) searches relating to activities outside the home — activities that could put people at risk of SARS-CoV-2 infection — and a rise in COVID-19 cases 10–14 days afterward. Infections fell when there was an increase in searches relating to stay-at-home activities...
https://www.medicalnewstoday.com/articles/how-google-search-data-can-predict-cov...

Anasse Bari et al. 2021. COVID-19 early-alert signals using human behavior alternative data. Social Network Analysis and Mining volume 11, Article number: 18 (04 February 2021) https://link.springer.com/article/10.1007/s13278-021-00723-5

Abstract
Google searches create a window into population-wide thoughts and plans not just of individuals, but populations at large. Since the outbreak of COVID-19 and the non-pharmaceutical interventions introduced to contain it, searches for socially distanced activities have trended. We hypothesize that trends in the volume of search queries related to activities associated with COVID-19 transmission correlate with subsequent COVID-19 caseloads. We present a preliminary analytics framework that examines the relationship between Google search queries and the number of newly confirmed COVID-19 cases in the United States. We designed an experimental tool with search volume indices to track interest in queries related to two themes: isolation and mobility. Our goal was to capture the underlying social dynamics of an unprecedented pandemic using alternative data sources that are new to epidemiology. Our results indicate that the net movement index we defined correlates with COVID-19 weekly new case growth rate with a lag of between 10 and 14 days for the United States at-large, as well as at the state level for 42 out of 50 states with the exception of 8 states (DE, IA, KS, NE, ND, SD, WV, WY) from March to June 2020. In addition, an increasing caseload was seen over the summer in some southern US states. A sharp rise in mobility indices was followed by a sharp increase, respectively, in the case growth data, as seen in our case study of Arizona, California, Florida, and Texas. A sharp decline in mobility indices is often followed by a sharp decline, respectively, in the case growth data, as seen in our case study of Arizona, California, Florida, Texas, and New York. The digital epidemiology framework presented here aims to discover predictors of the pandemic’s curve, which could supplement traditional predictive models and inform early warning systems and public health policies.

Videos in online publication:

Keiko Ishii et al. 2021. Relationship between human exhalation diffusion and posture in face-to-face scenario with utterance featured. Physics of Fluids 33, 027101 (2021); https://doi.org/10.1063/5.0038380

ABSTRACT
Because of the COVID-19, the world has been affected significantly. Not only health and medical problems but also the decline in life quality and economic activity due to the suspension of social activities cannot be disregarded. It is assumed that the virus is transmitted through coughing and sneezing; however, the possibility of airborne infection by aerosols containing viruses scattered in the air has become a popular topic recently. In airborne infections, the risk of infection increases when the mucous membrane is exposed to exhaled aerosols for a significant amount of time. Therefore, in this study, we visualize human breath using the smoke of electronic cigarettes as tracer particles. Exhalation when speaking was visualized for four human posture patterns. The result shows that the exhaled breath is affected by the body wall temperature; it rises when it remains in the boundary layer by wearing a mask. On the other hand, without a mask, it initially flows downward due to the structure of the nose and mouth, so it flows downward due to inertia and diffuses randomly. This finding is effective in reducing the risk of infection during face-to-face customer service.

IV. CONCLUSION
We visualized the actual human breath to obtain guidelines for social activities such as customer service while suppressing the risk of infection. The following conclusions were obtained:
• When not wearing a mask, the shape of the nose and mouth structure made exhaled air move downward due to inertia.
• By wearing a mask, when standing or sitting, the exhaled breath tends to reattach to the human body, and the aerosols flowed up along the body.
• When facing downward, the aerosols tended to separate from the temperature boundary layer of the human body. The exhaled air that has passed through the mask tends to move downward under the influence of the initial expiratory jet generated by the nose and mouth. Hence, it is effective to wear a face shield when liaising with a person below.
• When facing upward, the aerosols leaking from the upper part of the mask interfered with the exhaled air transmitted from the mask surface; furthermore, the aerosols were agitated and flowed in a complicated manner even when the mask was worn. Because the exhaled air flowed to the back, care must be established when contacting from behind.
• By wearing a non-woven mask, the injection of aerosols to the front was effectively suppressed.
Hence, in this study, we focused on the expiratory characteristics affected by the human body temperature and posture; additionally, we measured the flow field based on those characteristics.

The U.S. Is Making It Harder for the Rest of the World to Get COVID Vaccines
Jane C. Hu | Feb 22, 2021
https://slate.com/technology/2021/02/us-covid-vaccines-covax-global-south.html

______________________________________________

Not discussed:

1. the US has the most cases per capita and highly uneven non-pharmaceutical programs (masks), so for this disease at least, it is the most likely SOURCE of future dangerous variants for the world (however, if US was focused on suppressing cases rather than mortality, it would be assigning vaccines to 20-40 age group and not over-65s?);

2. Americans just ditched a leader who was failing them in COVID management. Canada's minority government is likewise under attack for failure thus far to provide purchased vaccines (Pfizer, Belgium). Democracy...

"...the risk of Covid-19 was about 2-3 times less in spectacles wearing population than the population not wearing those..."

Coronavirus: Glasses wearers less likely to get COVID, study says
ABC | February 23, 2021

...A new study out of India found people who wear glasses are three times less likely to get the virus.

Researchers suggest that's because they're less likely to touch their eyes-- which can be a significant route of infection.

A previous study conducted in China found just 5% of those hospitalized with COVID wore glasses, while about 30% of the population wears glasses...

https://abc7ny.com/covid-vaccine-glasses-wearing-during-and/10365580/

____________________________________________________

Amit Kumar Saxena Senior. 2021. Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India. MedRxiv (Feb 13, 2021). doi: https://doi.org/10.1101/2021.02.12.21249710
This article is a preprint and has not been peer-reviewed

Abstract
Introduction Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to compare the risk of COVID-19 in long term spectacles wearers with the risk in persons not using spectacles.

Objectives To know the association between infection with SARSCoV-2 and wearing of spectacles.

Materials and methods In this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour was assessed through a questionnaire. Spectacles wearing behaviour of general population was obtained from older studies (for comparison). Risk of COVID-19 was calculated in long term spectacles wearers as well as in persons not using spectacles. Chi-Square test was used for statistical analysis.

Results In this study, total 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. The risk of COVID-19 was found 0.48 in spectacles wearing population as compared to 1.35 in population not using spectacles. The calculated risk ratio was 0.36. The protective effectiveness of the spectacles was found statistically significant (p-value .00113).

Conclusion The present study showed that the risk of Covid-19 was about 2-3 times less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.

Thought-provoking read:

The scientist who’s been right about Covid-19 vaccines predicts what’s next
Hilda Bastian on the most important pandemic vaccine in the pipeline and why we’re on track for annual booster shots.
Julia Belluz@juliaoftoronto | Feb 24, 2021

Covid-19 arrogance
Vaccine hype
“The story of the pandemic”
How does this end?

https://www.vox.com/22285256/covid-19-vaccine-predictions

>60 margd: Re Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine . Krammer F et al. medRxiv. 2021 Feb 1. https://www.medrxiv.org/content/10.1101/2021.01.29.21250653v1.full.pdf

Is One Vaccine Dose Enough After COVID-19 Infection?
Dr. Francis Collins (NIH director) | February 23rd, 2021

...A small, NIH-supported study, published as a pre-print on medRxiv, offers some early data on this important question... The findings show that immune response to the first vaccine dose in a person who’s already had COVID-19 is equal to, or in some cases better, than the response to the second dose in a person who hasn’t had COVID-19. While much more research is needed—and I am definitely not suggesting a change in the current recommendations right now—the results raise the possibility that one dose might be enough for someone who’s been infected with SARS-CoV-2 and already generated antibodies against the virus.

...If other studies support these results, the U.S. Food and Drug Administration (FDA) might decide to consider whether one dose is enough for people who’ve had a prior COVID-19 infection. Such a policy is already under consideration in France and, if implemented, would help to extend vaccine supply and get more people vaccinated sooner. But any serious consideration of this option will require more data. It will also be up to the expert advisors at FDA and Centers for Disease Control and Prevention (CDC) to decide...

https://directorsblog.nih.gov/2021/02/23/is-one-dose-of-covid-19-vaccine-enough-...

FDA review confirms safety and efficacy of single-shot Johnson & Johnson coronavirus vaccine, especially against severe cases
Carolyn Y. Johnson and Laurie McGinley | Feb. 24, 2021

A Food and Drug Administration review released Wednesday of the single-shot coronavirus vaccine made by pharmaceutical giant Johnson & Johnson found it was safe and effective and completely prevented hospitalizations and deaths in a large clinical trial.

The review sets the stage for a third coronavirus vaccine to be authorized as soon as this weekend

...more than 85 percent effective at preventing severe illness, including in a region dominated by a concerning variant, but only 66 percent protective overall when moderate cases were included...vaccine efficacy against severe covid-19 “was similarly high across the United States, South Africa, and Brazil...less effective in a subgroup of adults older than 60 who also had risk factors for severe illness, but regulators noted there were no deaths or cases requiring medical intervention a month after those older adults received vaccines. Overall, there were seven deaths in the trial, all in the group that received a placebo.

The vaccine can be stored in a refrigerator for several months, which should ease the challenges of distributing frozen products, and it doesn’t require a follow-up visit for a booster shot.

https://www.washingtonpost.com/health/2021/02/24/johnson-and-johnson-vaccine/

Preliminary: NYC may have as many as two new variants, one of which has the E484K mutation that may partially evade vaccines (and antibodies from previous infection). The other has a mutation called S477N, which may affect how tightly the virus binds to human cells. 27% of viral sequences deposited into the NYC database have one or the other mutation, grouped together at the moment as B.1.526 variant. 12% have the E484K mutation. Data has not yet been released, much less peer-reviewed--two pre-preprints...

A New Coronavirus Variant Is Spreading in New York, Researchers Report
The variant contains a mutation thought to help the virus dodge the immune system, scientists said.
Apoorva Mandavilli | Feb. 24, 2021
https://www.nytimes.com/2021/02/24/health/coronavirus-variant-nyc.html

Again, based on a pre-preprint. Very preliminary info. New California strain B.1.427/B.1.429 may be more than three times more infectious than the original strain of SARS-CoV-2. By the end of March, B.1.427/B.1.429 will probably account for 90% of California's COVID cases.

"Dr. Anthony Fauci, the nation’s top infectious disease expert,...stop the spread of either (CA or UK) variant by getting vaccinated, wearing masks and limiting exposure to others."

The ‘nightmare scenario’ for California’s coronavirus strain: Here is what we know
Melissa Healy | Feb. 24, 2021
https://www.latimes.com/science/story/2021-02-24/the-nightmare-scenario-for-cali...

Great if vaccine somehow benefits long COVID patients, not just placebo effect. Let's hope!

Mara Gay* @MaraGay | 11:14 AM · Feb 24, 2021
This is both anecdotal and early,
but many long covid survivors are feeling significantly better after receiving their first vaccine dose.
Including me. Fascinating.

* Mara Gay @MaraGay: New York Times editorial board, covering politics and all things New York. MSNBC analyst. Subway rider and beachgoer. Go Blue.

_______________________________________________________

NEW: Dr. Fauci announces $1.15 billion in funding to study and improve care for people with lingering COVID symptoms (PASC).
Important news for so many who are struggling.
- Andy Slavitt (WH COVID Advisor) @aslavitt46 | 11:25 AM · Feb 24, 2021

Israel Gives Vaccine to Far-Off Allies, as Palestinians Wait
Patrick Kingsley | Feb. 23, 2021

The donations will go to nations like the Czech Republic and Honduras that pledged to move diplomats to Jerusalem. Critics say Israel has an obligation to inoculate Palestinians under its occupation...

...the governments of the Czech Republic and Honduras confirmed that Israel had promised them each 5,000 vaccine doses manufactured by Moderna. The Israeli news media reported that Hungary and Guatemala would be sent a similar number, but the Hungarian and Israeli governments declined to comment, while the Guatemalan government did not respond to a request for comment.

The donations are the latest example of a new expression of soft power: vaccine diplomacy, in which countries rich in vaccines seek to reward or sway those that have little access to them.

Jockeying for influence in Asia, China and India have donated thousands of vaccine doses to their neighbors. The United Arab Emirates has done the same for allies like Egypt. And last week, Israel even promised to buy tens of thousands of doses on behalf of the Syrian government, a longtime foe, in exchange for the return of an Israeli civilian detained in Syria...

https://www.nytimes.com/2021/02/23/world/middleeast/israel-palestinians-vaccine-...

Linsey Marr (Engineer prof VT) @linseymarr | 5:05 PM · Feb 24, 2021
https://twitter.com/linseymarr/status/1364697915357339649
I have no doubt that infection can happen via eyes and that large droplets can land there,
but aerosols are unlikely to deposit there.
If I assume 1 cm jet directed at eye, it must be 6000 mph for a 1 μm particle, 300 mph for 5 μm, 73 mph for 10 μm. /1

Quote Tweet
Eric Topol @EricTopol · Feb 23
Protecting the eyes from covid-19 described as "missing key" since, according to the authors, it's an under-appreciated route of #SARSCoV2 transmission; an interesting 1919 study w/ masks & atomized bacteria in solution, + other evidence
https://thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00040-9/fulltext
@LancetMicrobe
Image-article, highlighted ( https://twitter.com/EricTopol/status/1364369903545839619/photo/1 )
Image-article, highlighted ( https://twitter.com/EricTopol/status/1364369903545839619/photo/2 )

Aerosol scientists know that it's pretty hard to collect small aerosols by impaction;
need very high velocities and tight geometry. This was for Stokes number=1. Someone should check my calcs. /2

I still recommend eye protection for close contact situations to avoid large droplet spray. And stop rubbing your eyes! /3

Face shields also help divert aerosols in face-to-face conversations. /4

Nursing Homes, Once Hotspots, Far Outpace U.S. in Covid Declines
Matthew Conlen, Sarah Mervosh and Danielle IvoryFeb. 25, 2021

...The turnaround is an encouraging sign for vaccine effectiveness and offers an early glimpse at what may be in store for the rest of the country, as more and more people get vaccinated.

From late December to early February, new cases among nursing home residents fell by more than 80 percent, nearly double the rate of improvement in the general population. The trendline for deaths was even more striking: Even as fatalities spiked over all this winter, deaths inside the facilities have fallen, decreasing by more than 65 percent...

https://www.nytimes.com/interactive/2021/02/25/us/nursing-home-covid-vaccine.htm...
_________________________________________________________________

Remember how Dr. Fauci cautions the vacxxed not to lose their masks for a while yet?

Drop in Israel's COVID Infection Rates Comes to a Halt, Raising Concerns of Renewed Outbreak
Ido Efrati | Feb. 24, 2021

Israel's decline in coronavirus infection rates in recent weeks is slowing as concerns mount ahead of the Purim holiday and two and a half weeks after the country exited its third lockdown.

...R number – the average number of people each coronavirus carrier infects – (increased) from 0.83 to 0.9 in the past two days.

If this slight uptick in the spread of infection continues at the same pace, within days the R factor will rise above 1 which would mean that the infection rate is increasing rather than slowing down.

...it appears that the source of the rise in infections is not the school system. The data points to a decline in the infection rate among those 18 and under, through children in this age group are still a significant factor in the spread of the virus.

Due to the high immunization rate among the adult population, the composition of those infected and critically ill has changed in recent weeks. Children and adolescents aged 0 to 19 constitute more than 43 percent of all new patients, and those aged 20 to 39 constitute 35 percent of them.

One of the current goals of the ongoing vaccination campaign is to inoculate more young people....

Arab communities have also contributed to the rise in the infection rate, as their rate of inoculation is significantly lower than that of the entire country as a whole. The R factor in Arab communities has already hit the 1 mark, and the number of infected is about 20 percent of the non-Arab and non-Haredi population. In the Haredi (Orthodox Jewish sect) community the rate of inoculation among those 50 and over is 68 percent.

...Health Ministry officials worry about seeing significant violations of coronavirus regulations, particularly among the haredim, whose (Purim) parties may turn into large events involving mass alcohol-consumption.

https://www.haaretz.com/israel-news/drop-in-israel-s-covid-infection-rates-halts...

Moderna Announces it has Shipped Variant-Specific Vaccine Candidate, mRNA-1273.351, to NIH for Clinical Study
February 24, 2021 at 4:17 PM EST

Company also provides update on strategy for addressing SARS-CoV-2 variants of concern

Moderna, Inc....has completed manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant known as B.1.351 first identified in the Republic of South Africa, and has shipped doses to the National Institutes of Health (NIH) for a Phase 1 clinical trial that will be led and funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The Company also is providing an update on its strategy for addressing SARS-CoV-2 variants of concern.

While initial data confirms that the Moderna COVID-19 Vaccine (mRNA-1273) provides neutralizing activity against variants of concern, out of an abundance of caution, Moderna is pursuing two strategies against these variants, subject to U.S. Food and Drug Administration (FDA) review. First, the Company is evaluating booster doses of vaccine to increase neutralizing immunity against the variants of concern. Moderna plans to evaluate three approaches to boosting, including:

A variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in the Republic of South Africa, at the 50 µg dose level and lower.

A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower.

A third dose of mRNA-1273, the Moderna COVID-19 Vaccine, as a booster at the 50 µg dose level. The Company has already begun dosing this cohort with the booster.

Second, the Company plans to evaluate mRNA-1273.351 and mRNA-1273.211 as a primary vaccination series for those who are seronegative. These candidates will be evaluated in a two-dose series at the 100 µg dose level and lower.

Consistent with the recently updated FDA Guidance for Industry, the Company plans to evaluate immunogenicity and safety in participants who have not received a COVID-19 vaccine as well as participants in clinical studies who previously received the mRNA-1273 vaccine.

NIAID, part of the National Institutes of Health (NIH), will conduct a Phase 1 clinical trial to determine if mRNA-1273.351 can boost immunity against the variants of concern. Moderna will provide doses of mRNA-1273.351 to the NIH. NIAID will initiate this study after receiving safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins, and details will also be available on clinicaltrials.gov. In parallel, the Company will be conducting its own clinical studies to support regulatory filings for any booster vaccine or updated primary vaccine.

“We look forward to beginning the clinical study of our variant booster and are grateful for the NIH’s continued collaboration to combat this pandemic,” said Stéphane Bancel, Chief Executive Officer of Moderna. “As we seek to defeat COVID-19, we must be vigilant and proactive as new variants of SARS-CoV-2 emerge. Leveraging the flexibility of our mRNA platform, we are moving quickly to test updates to the vaccines that address emerging variants of the virus in the clinic. Moderna is committed to making as many updates to our vaccine as necessary until the pandemic is under control. We hope to demonstrate that booster doses, if necessary, can be done at lower dose levels, which will allow us to provide many more doses to the global community in late 2021 and 2022 if necessary.”

These studies will inform the Company’s regulatory strategy with the U.S. FDA and regulatory agencies outside of the U.S. The current Moderna COVID-19 Vaccine protocol calls for two 100 µg doses.

A letter to the editor in the New England Journal of Medicine published February 17, 2021, showed vaccination with the Moderna COVID-19 Vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7 and B.1.351, first identified in the UK and Republic of South Africa, respectively. The study showed no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. A six-fold reduction in neutralizing titers was observed with the B.1.351 variant relative to prior variants...

https://investors.modernatx.com/news-releases/news-release-details/moderna-annou...

Blood test for cell-Free DNA reveals cells, tissues, and organs injured related to COVID-19 severity: "We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19."


Alexandre Pellan Cheng et al. 2021. Cell-Free DNA Tissues of Origin by Methylation Profiling Reveals Significant Cell, Tissue, and Organ-Specific Injury Related to COVID-19 Severity. Med (January 16, 2021) DOI:https://doi.org/10.1016/j.medj.2021.01.001
https://www.cell.com/med/fulltext/S2666-6340(21)00031-3

Highlights

Blood test reported to quantify cell-, tissue-, and organ-specific injury due to COVID-19
Utility of test to identify subjects with severe disease assessed in two patient cohorts
Evidence reported of lung and liver injury and involvement of erythroblasts
Concentration of cell-free DNA was found to increase with disease progression

Context and Significance
COVID-19 is a systemic disease with multi-organ involvement. Here, the authors report a blood test to quantify cell-, tissue-, and organ-specific injury due to COVID-19. This is accomplished by profiling methylation marks within circulating cell-free DNA (cfDNA) to trace their tissues of origin and to quantify tissue-specific injury due to COVID-19. The authors assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients and report evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. These results support the utility of cfDNA profiling as a prognostic tool for the early detection and monitoring of cell and tissue injury due to COVID-19.

Summary
Background
Coronavirus disease 2019 (COVID-19) primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell-, tissue-, and organ-specific injury due to COVID-19.

Methods
Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls.

Findings
We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cell-free DNA correlated with the World Health Organization (WHO) ordinal scale for disease progression and was significantly increased in patients requiring intubation.

Conclusions
This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.

>86 margd: Moderna vaccine development plans. Here's Pfizer's:

A third Pfizer dose? The Covid-19 vaccine maker is studying booster shots.
Erika Edwards | Feb. 25, 2021

...The new study will monitor the safety and efficacy of a third dose in two age groups: those 18 to 55 and those 65 to 85. The participants come from a group of people who were among the first to receive the Pfizer-BioNTech vaccine: people who volunteered for Pfizer's initial Phase 1/2 clinical trial, which began in May.

During that trial, participants received two doses of the vaccine three weeks apart. The same dose interval is what's currently recommended.

The third shot will be exactly the same as what participants got a year ago.

( "Every year, you need to go to get your flu vaccine," (Pfizer CEO Albert Bourla ) said. "It's going to be the same with Covid. In a year, you will have to go and get your annual shot for Covid to be protected." )

...Pfizer also plans to begin testing whether a modified version of the vaccine works well against the variant from South Africa.

...So far, evidence suggests that the existing Pfizer-BioNTech vaccine remains effective against variants first identified in the U.K., Brazil and South Africa...

https://www.nbcnews.com/health/health-news/third-pfizer-dose-covid-19-vaccine-ma...

Single dose of Pfizer vaccine offers robust protection for those who have had Covid-19, studies find.
Benjamin Mueller | Feb. 26, 2021

For people who have had Covid-19, a single dose of the Pfizer vaccine is enough to provide robust protection from the coronavirus, according to two new studies from Britain that were published late Thursday in The Lancet, a prominent medical journal.

The studies, among the first fully vetted papers to weigh in on how to vaccinate people who have had Covid-19, added strong evidence to the case for giving just one dose of the Pfizer vaccine to people who already have antibodies against the virus...

https://www.nytimes.com/2021/02/26/world/pfizer-vaccine-protection.html
------------------------------------------------------------------------

Maria Prendecki et al. 2021. Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine. The Lancet. Published Online February 25, 2021. https://doi.org/10.1016/ S0140-6736(21)00502-X https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900502-X

Charlotte Manisty et al. Feb 25, 2021. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals. The Lancet. Published Online February 25, 2021. https://doi.org/10.1016/ S0140-6736(21)00501-8 https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900501-8
________________________________________________________

Below, Krammer pushes back (gently) on "among the first fully vetted papers" Scientists... :/
Still, great news for making vaccine supplies go further, quickly.

Florian Krammer (virologist) @florian_krammer| 6:54 AM · Feb 26, 2021:
Oh, really?

Florian Krammer et al. Feb 1, 2021. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. MedRxiv doi: https://doi.org/10.1101/2021.01.29.21250653 https://medrxiv.org/content/10.1101/2021.01.30.21250843v5

Amber R. Cornelius​ et al. February 9, 2021. Poor antigen-specific responses to the secondBNT162b2 mRNA vaccine dose inSARS-CoV-2-experienced individuals. MedRxiv doi: https://medrxiv.org/content/10.1101/2021.02.07.21251311v1.full.pdf https://doi.org/10.1101/2021.02.07.21251311

Riccardo Levi et al. Feb 6, 2021. A cautionary note on recall vaccination in ex-COVID-19 subjects. MedRxiv doi: https://doi.org/10.1101/2021.02.01.21250923 https://medrxiv.org/content/10.1101/2021.02.01.21250923v2

Kamal Abu Jabal etal. Feb 11, 2021. Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021. Eurosurveillance Volume 26, Issue 6, 11/Feb/2021 https://eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.6.2100096

Julie Czartoski et al. February 8, 2021. Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1.MedRxiv. doi: https://doi.org/10.1101/2021.02.05.21251182 https://medrxiv.org/content/10.1101/2021.02.05.21251182v1.full.pdf

Why Does the Pandemic Seem to Be Hitting Some Countries Harder Than Others?
While the virus has ravaged rich nations, reported death rates in poorer ones remain relatively low. What probing this epidemiological mystery can tell us about global health.

Siddhartha Mukherjee | February 22, 2021

...an epidemiological mystery. The usual trend of death from infectious diseases—malaria, typhoid, diphtheria, H.I.V.—follows a dismal pattern. Lower-income countries are hardest hit, with high-income countries the least affected. But if you look at the pattern of COVID-19 deaths reported per capita—deaths, not infections—Belgium, Italy, Spain, the United States, and the United Kingdom are among the worst off. The reported death rate in India, which has 1.3 billion people and a rickety, ad-hoc public-health infrastructure, is roughly a tenth of what it is in the United States. In Nigeria, with a population of some two hundred million, the reported death rate is less than a hundredth of the U.S. rate. Rich countries, with sophisticated health-care systems, seem to have suffered the worst ravages of the infection. Death rates in poorer countries—particularly in South Asia and large swaths of sub-Saharan Africa—appear curiously low. (South Africa, which accounts for most of sub-Saharan Africa’s reported COVID-19 deaths, is an important exception.)

...Bangladesh (a hundred and sixty-three million people; eighty-three hundred reported COVID-19 deaths, or 3.5 per cent of America’s, on a per-capita basis), studies populations and health.

...With respect to the raw numbers, underreporting is an enormous problem; differences in age distribution, too, make a very deep cut, and perhaps the models must further calibrate their weightings here. Plainly, certain countries have benefitted from the strength of their public-health systems, fortified by a vigorous government response.

... When it comes to a crisis that combines social and biological forces, we’ll do well to acknowledge the causal patchwork. What’s needed isn’t Ockham’s razor but Ockham’s quilt.

Above all, what’s needed is humility in the face of an intricately evolving body of evidence. The pandemic could well drift or shift into something that defies our best efforts to model and characterize it. As Patrick Walker, of Imperial College London, stressed, “New strains will change the numbers and infectiousness even further.” That quilt itself may change its shape...

https://www.newyorker.com/magazine/2021/03/01/why-does-the-pandemic-seem-to-be-h...

>82 margd: Interesting Twitter thread re anecdotal evidence that vaccine may provide relief to maybe 40% of long COVID convalescents!

Mara Gay (NYT Bd) @MaraGay | 11:14 AM · Feb 24, 2021:
This is both anecdotal and early, but many long covid survivors are feeling significantly better after receiving their first vaccine dose. Including me. Fascinating.

Apoorva Mandavilli (NYT) @apoorva_nyc | 11:31 AM · Feb 24, 2021:
So interesting! Are others seeing this happen as well?

Daniel Griffin MD PhD @DanielGriffinMD | 1:01 PM · Feb 24, 2021
https://twitter.com/DanielGriffinMD/status/1364636521123487744
Seeing this myself and hearing this from many of my colleagues. Would love to see data but my estimate is about 40% of our Long COVID patients feel improved after first and now second vaccination. Maybe Shane Crotty or Akiko have ideas on why?

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 4:29 PM · Feb 25, 2021
This is very promising! I am happy to see this coming up more and more. Perhaps Ab and T cells induced by the vaccines eliminate a reservoir of virus that is leading to long COVID symptoms (for example CNS). Fascinating!

Boeing 737 study tracks particles released by coughing from a passenger seated in different seats:

Angela C. Davis et al. 2021. Computational Fluid Dynamics Modeling of Cough Transport in an Aircraft Cabin. BioRxiv (Feb 17, 2021) doi: https://doi.org/10.1101/2021.02.15.431324
This article is a preprint and has not been certified by peer review.

Abstract

To characterize the transport of respiratory pathogens during commercial air travel, Computational Fluid Dynamics simulations were performed to track particles released by coughing from a passenger seated in different seats on a Boeing 737 aircraft. Simulation data were post-processed to calculate the amounts of particles inhaled by nearby passengers. Different airflow rates were used, as well as different initial conditions to account for random fluctuations of the flow field. Overall, 80% of the particles were removed from the cabin in 1.3 to 2.6 minutes, depending on conditions, and 95% of the particles were removed in 2.3 to 4.5 minutes. Reducing airflow increased particle dispersion throughout the cabin but did not increase the highest exposure of susceptible passengers. The highest exposure was 0.3% of the total nonvolatile mass emitted by the cough, with average exposure of 0.05%, in line with recent experimental testing reported in literature.

Why Opening Windows Is a Key to Reopening Schools (Interactive
Nick Bartzokas, Mika Gröndahl, Karthik Patanjali, Miles Peyton, Bedel Saget and Umi SyamFeb. 26, 2021

The C.D.C. is urging communities to reopen schools as quickly as possible, but parents and teachers have raised questions about the quality of ventilation available in public school classrooms to protect against the coronavirus.

We worked with a leading engineering firm and experts specializing in buildings systems to better understand the simple steps schools can take to reduce exposure in the classroom.

Here’s a typical classroom...

https://www.nytimes.com/interactive/2021/02/26/science/reopen-schools-safety-ven...

>93 margd: ventilation in schools, per CDC

Ventilation in Schools and Child Care Programs
How to use CDC building recommendations in your setting
Updated Feb. 26, 2021

...
Bring in as much outdoor air as possible.
If safe to do so, open windows and doors. Even just cracking open a window or door helps increase outdoor airflow, which helps reduce the potential concentration of virus particles in the air. If it gets too cold or hot, adjust the thermostat. Do not open windows or doors if doing so poses a safety or health risk (such as falling, exposure to extreme temperatures, or triggering asthma symptoms).
Use child-safe fans to increase the effectiveness of open windows. Safely secure fans in a window to blow potentially contaminated air out and pull new air in through other open windows and doors.
Consider having activities, classes, or lunches outdoors when circumstances allow.

Ensure Heating, Ventilation, and Air Conditioning (HVAC) settings are maximizing ventilation.
Make sure your ventilation systems are serviced and meeting code requirements. They should provide acceptable indoor air quality, as defined by ASHRAE Standard 62.1external icon, for the current occupancy level for each space.* Home-based child care programs should meet requirements established by their state and local regulatory authorities.
Set HVAC systems to bring in as much outdoor air as your system will safely allow. Reduce or eliminate HVAC air recirculation, when practical and with expert HVAC consultation.*
Increase the HVAC system’s total airflow supply to occupied spaces when you can. More air flow encourages air mixing and ensures any recirculated air passes through the filter more frequently.
Disable demand-controlled ventilation (DCV) controls that reduce air supply based on occupancy or temperature. This way the air supply will remain constant throughout the day.
For simple HVAC systems controlled by a thermostat, setting the fan control switch from “Auto” to “On” will ensure the HVAC system provides continuous air filtration and distribution.
Consider running the HVAC system at maximum outside airflow for 2 hours before and after the building is occupied to refresh air before arrival and remove remaining particles at the end of the day.

Good Cafe Ventilation
Good ventilation is important, especially in areas where students may not be able to wear masks. Eating meals outside is best. If you need to have students eat in a cafeteria, use methods such as opening windows, maximizing filtration as much as the system will allow and using portable HEPA air cleaners.

Filter and/or clean the air in your school or child care program.
Improve the level of air filtration as much as possible without significantly reducing airflow.
Make sure the filters are sized, installed, and replaced according to manufacturer’s instructions.
Consider portable air cleaners that use high-efficiency particulate air (HEPA) filters to enhance air cleaning wherever possible, especially in higher-risk areas such as a nurse’s office or sick/isolation room.
Consider using ultraviolet germicidal irradiation (UVGI) in schools and non-home-based child care programs as a supplemental treatment to inactivate the virus that causes COVID-19, especially if options for increasing ventilation and filtration are limited. Consult a qualified professional to help design and install any UVGI system.

School bus with children
Opening vehicle windows even a little bit can improve ventilation.

Use exhaust fans in restrooms and kitchens.
Inspect and maintain exhaust ventilation systems in restrooms and kitchens.
Ensure restroom and kitchen exhaust fans are on and operating at full capacity while the school or child care program is occupied and for 2 hours afterward.

Open windows in transportation vehicles.
Ventilation is important on buses and vans servicing schools and child care programs, along with other strategies such as mask use for people over 2 years old and physical distancing.
Keep vehicle windows open when it does not create a safety or health hazard. Having more windows open is more helpful, but even just cracking a few windows open is better than keeping all windows closed.

https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/ventilatio...

Summary of the 5 Phase 3 vaccine trials.
One theme: 100% protection from death and hospitalizations
That is impressive!
Image ( https://twitter.com/EricTopol/status/1364703838100316162/photo/1 )

One footnote on the J&J trial data today.
The analysis for deaths and hospitalizations (H) was post-hoc (not pre-planned) and
the prevention was 100% ≥28 days post-vaccine.
Prior to that there were some H events as shown in the Table.
No deaths in the vaccine arm (7 in placebo)
Image ( https://twitter.com/EricTopol/status/1364738123062632448/photo/1 )

- Eric Topol @EricTopol | 5:28 PM · Feb 24, 2021

Philippines receives COVID-19 vaccine after delays
JIM GOMEZ | Feb 28, 2021

...Aside from the donated vaccine (600,000 doses) from Sinovac Biotech, the government has separately ordered 25 million doses from the China-based company. An initial 525,600 doses of COVID-19 vaccine from AstraZeneca were also scheduled to arrive Monday...

The initial deliveries are a small fraction of at least 148 million doses the government has been negotiating to secure from Western and Asian companies to vaccinate about 70 million Filipinos for free in a massive campaign largely funded with foreign and domestic loans. The bulk of the vaccine shipments are expected to arrive later this year.

...Duterte’s administration has come under criticism for lagging behind most other Southeast Asian countries in securing the vaccines, including much smaller and poorer ones like Cambodia, Myanmar and Laos.

The tough-talking Duterte has said wealthy Western countries, especially where the vaccine originated, have cornered massive doses for their citizens, leaving poorer nations scrambling to get the rest. In a sign of desperation, the president said last December that he would proceed to abrogate a key security pact with the United States that allows large numbers of American troops to conduct war exercises in the Philippines if Washington could not provide at least 20 million doses of COVID-19 vaccine for his country.

...The Chinese vaccine delivery was delayed due to the absence of an emergency-use authorization from Manila’s Food and Drug Administration. Sinovac got the authorization last Monday. Western pharmaceutical companies also wanted the Philippine government to guarantee that it would take responsibility for lawsuits and demands for indemnity arising from possible adverse side effects from the vaccine...Duterte signed a law last week giving pharmaceutical companies immunity from such liabilities for the emergency use by the public of their vaccine.

https://apnews.com/article/cabinets-philippines-coronavirus-pandemic-asia-east-a...

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Thailand Kicks Off Covid-19 Vaccine Program With Sinovac Shots
Anuchit Nguyen | February 27, 2021

...Thailand started rolling out its Covid-19 inoculation program with Sinovac Biotech Ltd.’s vaccine as the Southeast Asian nation tries to revive its pandemic-hit tourism industry.

...Southeast Asia’s second-biggest economy aims to inoculate 50% of its population by the end of this year as the government tries to reopen its borders, which have been closed for almost a year to curb the outbreak. The government has also approved AstraZeneca Plc’s vaccine and has ordered 61 million doses.

...AstraZeneca’s vaccine arrived in Thailand on Feb. 24 but the company still needs to complete the quality-assurance process...

https://www.bloomberg.com/news/articles/2021-02-28/thailand-kicks-off-covid-19-v...

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(US) FDA Grants Emergency Use Authorization For Third Covid-19 Vaccine in U.S.
NBC Nightly News • Feb 27, 2021

The FDA has issued emergency use authorization for Johnson & Johnson’s Covid-19 vaccine. Roughly 4 million doses could be shipped as early as Monday.

https://www.youtube.com/watch?v=xB9MD-XYYb4

In Hunt for Covid-19 Origin, Patient Zero Points to Second Wuhan Market
The man with the first confirmed infection of the new coronavirus told the WHO team that his parents had shopped there
Jeremy Page, Drew Hinshaw, Betsy McKay | Feb. 26, 2021

World Health Organization investigators are seeking information about a second food market in the Chinese city of Wuhan after the first officially confirmed Covid-19 case, dubbed patient zero, told them his parents had shopped there.

Chinese authorities have said since early last year that the first confirmed victim was a Wuhan resident surnamed Chen who fell sick on Dec. 8, 2019, and had no connection to the Huanan seafood market, which was tied to many of the early infections.

That case, and more recent evidence, led a WHO team probing the pandemic’s origins to conclude that the virus might have first jumped from an animal to a human earlier, and elsewhere, and been spreading throughout Wuhan by the time an outbreak at the Huanan market occurred.

The putative patient zero met the WHO investigators during their recent four-week visit to Wuhan, and told them that his parents had visited another local community food market, according to three team members...

https://www.wsj.com/articles/in-hunt-for-covid-19-origin-patient-zero-points-to-...

1. Lilly monoclonal antibody "bamlanivimab may not provide efficacy against SARS-CoV-2 variants harboring the E484K substitution." (e.g., S African, Brazil, and--not studied here, NY--variants of concern) Confirmation of the SARS-CoV-2 variant, including screening for E484K, may be needed before initiating mAb treatment with bamlanivimab to ensure both efficacious and efficient use of the antibody product. Hence, variant-specific mAb agents may be required to treat emerging VOC." (Widera et al. 2021)

2. Sounds like Lilly and Pfizer, at least, may need to rejigger their products to counter any emergence of E484K mutation: "entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab (Regeneron antibody "cocktail")) or fully (Bamlanivimab (lilly monoclonal antibody)) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 (Pfizer BioNTech) vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic." (Hoffman et al. 2021)

*******************************************************************

Marek Widera et al. 2021. Bamlanivimab does not neutralize two SARS-CoV-2 variants carrying E484K in vitro. MedRxiv (Feb 26, 2021) doi: https://doi.org/10.1101/2021.02.24.21252372 https://www.medrxiv.org/content/10.1101/2021.02.24.21252372v1

This article is a preprint and has not been certified by peer review.

Abstract
The IgG1 monoclonal antibody (mAb) bamlanivimab (LY-CoV555) prevents viral attachment and entry into human cells by blocking attachment to the ACE2 receptor. However, whether bamlanivimab is equally effective against SARS-CoV-2 emerging variants of concern (VOC) is not fully known. Hence, the aim of this study was to determine whether bamlanivimab is equally effective against SARS-CoV-2 emerging VOC. The ability of bamlanivimab to neutralize five SARS-CoV-2 variants including B.1.1.7 (mutations include N501Y and del69/70), B.1.351 (mutations include E484K and N501Y) and P.2 (mutations include E484K in the absence of a N501Y mutation) was analyzed in infectious cell culture using CaCo2 cells. Additionally, we analyzed vaccine-elicited sera after immunization with BNT162b2, and convalescent sera for its ability to neutralize SARS-CoV-2 variants. We found that the variant B.1.1.7, as well as two isolates from early 2020 (FFM1 and FFM7) could be efficiently neutralized by bamlanivimab (titer 1/1280, respectively), however, no neutralization effect could be detected against either B.1.135 or P.2, both harboring the E484K substitution. Vaccine-elicited sera showed slightly decreased neutralizing activity against B1.1.7, B.1.135 and P.2 Our in vitro findings indicate that, in contrast to vaccine-elicited sera, bamlanivimab may not provide efficacy against SARS-CoV-2 variants harboring the E484K substitution. Confirmation of the SARS-CoV-2 variant, including screening for E484K, may be needed before initiating mAb treatment with bamlanivimab to ensure both efficacious and efficient use of the antibody product. Hence, variant-specific mAb agents may be required to treat emerging VOC.

Image-table ( https://twitter.com/ncholiA/status/1366174007280680966/photo/1 )

-------------------------------------------------------------

Markus Hoffmann et al. 2021. SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination. BioRxiv (Feb 11, 2021) doi: https://doi.org/10.1101/2021.02.11.430787 https://www.biorxiv.org/content/10.1101/2021.02.11.430787v1

SUMMARY
The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic.

Image-graphs of bamlanivimab v wild, S Africa, UK, Brazil strains ( https://twitter.com/r_gross_/status/1366284056384724995/photo/1 )

Rastaphrog,

Retail stores: "the rate of direct transmission under full compliance with one-way movement is less than one-third the rate under two-way movement...not effective if wake exposure dominates...two other interventions—reducing the speed variance of customers and throughput control—can be effective whether direct or wake transmission is dominant... the optimal throughput rate drops rapidly as the population prevalence rises."

Robert A. Shumsky et al. 2021. Retail store customer flow and COVID-19 transmission. PNAS March 16, 2021 118 (11) e2019225118; https://doi.org/10.1073/pnas.2019225118 https://www.pnas.org/content/118/11/e2019225118

Significance

To reduce the transmission of COVID-19, many retail stores use one-way aisles, while local governments enforce occupancy limits or require “safe shopping” times for vulnerable groups. To assess the value of these interventions, we formulate and analyze a mathematical model of customer flow and COVID-19 transmission. We find that the value of specific operational changes depends on how the virus is transmitted, through close contact or suspended aerosols. If transmission is primarily due to close contact, then restricting customers to one-way movement can dramatically reduce transmission. Other interventions, such as reductions in customer density, are effective at a distance but confront store operators with trade-offs between infection rates and customer flow.

Abstract
We examine how operational changes in customer flows in retail stores affect the rate of COVID-19 transmission. We combine a model of customer movement with two models of disease transmission: direct exposure when two customers are in close proximity and wake exposure when one customer is in the airflow behind another customer. We find that the effectiveness of some operational interventions is sensitive to the primary mode of transmission. Restricting customer flow to one-way movement is highly effective if direct exposure is the dominant mode of transmission. In particular, the rate of direct transmission under full compliance with one-way movement is less than one-third the rate under two-way movement. Directing customers to follow one-way flow, however, is not effective if wake exposure dominates. We find that two other interventions—reducing the speed variance of customers and throughput control—can be effective whether direct or wake transmission is dominant. We also examine the trade-off between customer throughput and the risk of infection to customers, and we show how the optimal throughput rate drops rapidly as the population prevalence rises.

5 Pandemic Mistakes We Keep Repeating
We can learn from our failures.
Zeynep Tufekci | February 26, 2021

Risk Compensation
Even if safety improvements cause a few people to behave recklessly, the benefits overwhelm the ill effects.

Rules in Place of Mechanisms and Intuitions
Our public guidelines should have been more like Japan’s, which emphasize avoiding the three C’s—closed spaces, crowded places, and close contact—that are driving the pandemic.

Scolding and Shaming
While visible but low-risk activities attract the scolds, other actual risks—in workplaces and crowded households, exacerbated by the lack of testing or paid sick leave—are not as easily accessible to photographers.

Harm Reduction
Harm reduction is the recognition that if there is an unmet and yet crucial human need (e.g. socializing), we cannot simply wish it away; we need to advise people on how to do what they seek to do more safely. Risk can never be completely eliminated; life requires more than futile attempts to bring risk down to zero.

The Balance Between Knowledge And Action
In academia, publishing is the coin of the realm, and it is often done through rejecting the null hypothesis—meaning that many papers do not seek to prove something conclusively, but instead, to reject the possibility that a variable has no relationship with the effect they are measuring (beyond chance)...At crucial points during the pandemic, though, this resulted in mistranslations and fueled misunderstandings, which were further muddled by differing stances toward prior scientific knowledge and theory...seasonality, the key role of overdispersion, and aerosol transmission...presymptomatic transmission...(good news) vaccines...restaurants...inequality...

...We should encourage people to dream about the end of this pandemic by talking about it more, and more concretely: the numbers, hows, and whys. Offering clear guidance on how this will end can help strengthen people’s resolve to endure whatever is necessary for the moment—even if they are still unvaccinated—by building warranted and realistic anticipation of the pandemic’s end.

Hope will get us through this. And one day soon, you’ll be able to hop off the subway on your way to a concert, pick up a newspaper, and find the triumphant headline: “COVID Routed!”

https://www.theatlantic.com/ideas/archive/2021/02/how-public-health-messaging-ba...

>80 margd: contd.

Variant B.1.526 expands reach in NY (25%) and northeast US (735 cases): patients on average older and more frequently hospitalized
E484K mutation (also in S Africa & Brazil strains) evades (Lilly, prior infection) antibodies, reduces somewhat at least vaccine efficacy.
Important to quickly vaccinate and maintain defenses (masks, social distancing) in next couple months at least.
_________________________________________________________________

Eric Topol @EricTopol | 9:49 PM · Mar 1, 2021:
The New York variant, B.1.526, w/ 2 preprints supporting its immune evasion property, first reported on by @apoorva_nyc, is the subject of more concern

NY COVID-19 Variant Expands Reach in US with 735 Cases
Emma Court, Josh Wingrove and Jordan Fabian | March 1, 2021
Image-from Bloomberg article (https://twitter.com/EricTopol/status/1366581304800669700/photo/1)
https://bloomberg.com/news/articles/2021-03-01/new-york-covid-19-variant-drawing...

https://nytimes.com/2021/02/24/health/coronavirus-variant-nyc.html (>80 margd:)

https://biorxiv.org/content/10.1101/2021.02.14.431043v2.article-info *

https://medrxiv.org/content/10.1101/2021.02.23.21252259v1.full.pdf **

Immune evasion ≠ vaccine resistance
The E484K (eek) mutation that may be driving its Δ response to monoclonal antibodies in vitro is also found in P.1 (Brazil) and B.351 (South Africa) to which vaccines (J&J, Novavax) have shown preserved (w/ some reduction) of efficacy

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* Anthony P. West Jr. et al. 2021. SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape. Bio Rxiv (23 Feb 2021) doi: https://doi.org/10.1101/2021.02.14.431043 https://biorxiv.org/content/10.1101/2021.02.14.431043v2.article-info

This article is a preprint and has not been certified by peer review.

Abstract
Wide-scale SARS-CoV-2 genome sequencing is critical to monitoring and understanding viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We have developed a software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using this tool, we detected an emerging lineage of viral isolates in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage appeared in late November 2020, and isolates from this lineage account for ~25% of coronavirus genomes sequenced and deposited from New York during February 2021.

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** Hiroshi Mohri et al. 2021. A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York. MedRxiv ( February 25, 2021) https://doi.org/10.1101/2021.02.23.21252259 https://www.medrxiv.org/content/10.1101/2021.02.23.21252259v1.full.pdf

Preprint

Abstract
Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7 (UK), B1.351 (S Africa), and P.1 (Brazil) have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

Heart damage found in half of COVID-19 patients discharged after hospitalisation
Maxine Myers | 01 March 2021

...Dr Graham Cole lead author of the study from the National Heart and Lung Institute at Imperial College London and Consultant Cardiologist at Imperial College Healthcare NHS Trust, said: "These findings have confirmed further complications and outcomes for hospitalised patients with severe COVID-19. Many of these patients have underlying health conditions and may experience further problems after recovering from COVID-19. The study shows that MRI scans of the heart are useful in patients with COVID-19 whose troponin was raised.”

Troponin is released into the bloodstream after a heart attack. Raised levels can occur when an artery becomes blocked or there is inflammation of the heart. Many patients who are hospitalised with COVID-19 have raised troponin levels during the critical illness phase, when the body mounts an exaggerated immune response to the infection.

...Patients who had abnormal troponin levels were offered an MRI scan of the heart a month or two after discharge to see if there was any damage to the heart. The results were compared with those from a control group of patients who had not had COVID-19 but were matched for age and other comorbidities such as hypertension and diabetes, as well as from 40 healthy volunteers.

Heart damage
The researchers found evidence of heart muscle injury that could be seen on the scans a month or two after discharge. The function of the heart’s left ventricle, the chamber that is responsible for pumping oxygenated blood to all parts of the body, was normal in 131 of the 148 patients but scarring, injury to the heart muscle or problems with the heart’s blood supply was present in 80 patients. The pattern of tissue scarring, or injury originated from inflammation in 39 patients, from ischaemic heart disease, which includes infarction or ischaemia, in 32 patients, and from both in nine patients. Twelve patients appeared to have ongoing heart inflammation.

Although some of the heart damage may have been pre-existing, the researchers suggest that some of the damage was new and likely caused by COVID-19. In the most severe cases, there are concerns that this injury may increase the risks of heart failure in the future, but more work is needed to investigate this further.

Further work
The researchers also suggest that the findings from the study could be used to identify patients at higher or lower risk and suggest potential strategies that may improve outcomes.

The findings from the study only included patients who survived a coronavirus infection that required hospital stays. The team believe that more work needs to be done to explore the impact of COVID-19 on patients who had COVID-19 but were not hospitalised and those who are hospitalised but without elevated troponin to see if COVID-19 has an impact on long-term heart health.

https://www.imperial.ac.uk/news/216033/heart-damage-found-half-covid-19-patients...

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Tushar Kotecha et al. 2021. Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance. European Heart Journal (18 February 2021), ehab075, https://doi.org/10.1093/eurheartj/ehab075 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab075...

Abstract
Background...

Methods and results
One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection {all requiring hospital admission, 48 (32%) requiring ventilatory support} and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions
During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Juan Camilo Castillo et al. 2021. Market design to accelerate COVID-19 vaccine supply. Science 25 Feb 2021: eabg0889
DOI: 10.1126/science.abg0889 https://science.sciencemag.org/content/early/2021/02/24/science.abg0889

Abstract
Build more capacity, and stretch what we already have

Each month, COVID-19 kills hundreds of thousands of people, reduces global gross domestic product (GDP) by hundreds of billions of dollars, and generates large, accumulating losses to human capital by harming education and health (1–4). Achieving widespread immunization 1 month faster would thus save many lives and mitigate short- and long-run economic harm. Although the value of vaccines may seem obvious, government action and investment in vaccines have not been commensurate with the enormous scale of benefits, with many countries not likely to achieve widespread immunization until the end of 2022.

We estimate below that installed capacity for 3 billion annual vaccine courses has a global benefit of $17.4 trillion, over $5800 per course. Investing now in expanding capacity for an additional annual 1 billion courses could accelerate completion of widespread immunization by over 4 months, providing additional global benefits of $576 to $989 per course. This dwarfs prices of $6 to $40 per course seen in deals with vaccine producers, indicating the wide gap between social and commercial incentives. We urge governments and international organizations to contract with vaccine producers to further expand capacity and encourage measures described below to “stretch” existing capacity (such as lower-dose regimens) and efficiently allocate courses (such as a cross-country vaccine exchange).

VALUE OF CAPACITY IN PLACE

VALUE OF ADDITIONAL CAPACITY

MARKET-DESIGN PRINCIPLES
Contract on capacity versus output
Relax supply-chain constraints
Solicit bids

USING CAPACITY EFFICIENTLY
Dosing regimens
Vaccine trials
Utilizing lower-efficacy vaccines
Cross-country vaccine exchange

UNPRECEDENTED CAPACITY
Even though unprecedented vaccine capacity has been put in place for COVID-19, expanding capacity yet further would generate substantial global benefits. Standing manufacturing capacity that can be repurposed quickly to produce vaccines and complementary inputs has a very high social value, in the current pandemic and in expectation of outbreaks to come. Capacity can even be an antidote to conflicts over distribution—which countries get scarce vaccines first and which people—by speeding up widespread vaccination. But markets will not deliver this capacity on their own.

https://science.sciencemag.org/content/early/2021/02/24/science.abg0889

Eric Feigl-Ding 14 tweets
https://threadreaderapp.com/thread/1366619383997607941.html
UNDERRATED BENEFITS of J&J vaccine on severe illness— lost in efficacy comparisons is how the J&J vaccine efficacy actually may **get better over time** for severe #COVID19–as high as 90-95% at 56 days—trend is very strong. And makes J&J on par w/ Pfizer-BioNTech & NIH-Moderna

from Twitter thread https://twitter.com/DrEricDing/status/1366619383997607941

ETA:
Jason Furman (Harvard Prof of Practice) @jasonfurman | 10:30 PM · Mar 1, 2021:
https://twitter.com/jasonfurman/status/1366591736332623873

If I had a choice btwn J&J & Moderna/Pfizer, I would take Moderna/Pfizer.
If I had a choice btwn J&J now and Moderna/Pfizer thirty minutes from now I would wait 30 minutes to take Moderna/Pfizer.
If the choice was J&J now vs. Moderna/Pfizer a year from now I would take J&J now.

Increased Risk of COVID-19 Transmission in Indoor Ice Rinks
Yale School of Public Health | Accessed March 2, 2021

Air flow and thermal inversion
COVID-19 circulation
Heating, ventilation and air conditioning
Risk models

Conclusions
1. Poor air quality and movement and mixing of the air can lead to elevated levels of airborne contaminants at the breathing height of skaters on the ice pad;
2. Temperature and humidity conditions inside ice arenas are within the range of conditions that may increase the survival of SARS-CoV-2 in aerosol;
3. Co-exposure to elevated levels of air pollutants, such as fine particulates and nitrogen dioxide, may worsen the severity of COVID infection;
4. Highly aerobic activity like skating will enhance respiration rate, increasing the release of potentially infectious aerosol if COVID-19 infected individuals are on the ice; and,
5. Highly aerobic activity will also enhance the risk of transmitting SARS-CoV-2 through increased breathing in of airborne contaminants.

It’s reasonable to suspect that the use of indoor ice arenas will increase the exposure of skaters to SARS-CoV-2 aerosols. Athletic activities inside ice arenas may pose an increased risk of COVID-19 transmission compared to athletic activities in other indoor and outdoor environments.

https://publichealth.yale.edu/research_practice/interdepartmental/covid/schools/...

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(Krystal Pollitt?). Feb 2, 2020. Return to Play? Increased Risk of COVID-19 Transmission in Indoor Ice Rinks. Yale School of Public Health (White Paper) 4 p. https://publichealth.yale.edu/research_practice/interdepartmental/covid/schools/...

Deen Freelon @dfreelon | 9:22 AM · Mar 1, 2021:
Black vax hesitancy makes headlines,
but the most reluctant group by far is white Republicans--a much larger group.

Republicans are least likely to want the coronavirus vaccine
Caitlin Owens | Feb 25, 2021
https://axios.com/republicans-coronavirus-vaccine-hesitancy-023bf32f-3d68-4206-b...

Image-Dec-Feb graph of vaccine-hesitant wh Rs, Blacks, Hispanics, wh Ds
( https://twitter.com/dfreelon/status/1366393501563441153/photo/1 )

Under a White House-brokered deal, Merck will help boost supplies of its rival Johnson & Johnson’s vaccine.
NYT | March 2, 2021

The pharmaceutical giant Merck & Co will help manufacture the new Johnson & Johnson coronavirus vaccine under a highly unusual deal, brokered by the White House. The move could substantially increase the supply of the new vaccine and ramp up the pace of vaccination just as worrisome new variants of the virus are taking hold in the United States.

...Merck is an experienced vaccine manufacturer whose own attempt at making a coronavirus vaccine was unsuccessful. Officials described the partnership between the two competitors as “historic,” and said it harkens back to Mr. Biden’s vision of a wartime effort to fight the coronavirus, similar to the manufacturing campaigns waged during World War II.

According to one official involved, the administration has been scouring the manufacturing landscape for weeks, ever since it became evident that Johnson & Johnson’s was running behind on its manufacturing. But just how quickly Merck will be able to ramp up is unclear. It will take months for the company to be able to convert its facilities to manufacture and package a vaccine that it did not invent.

...The president is invoking the Defense Production Act to help Merck retrofit its facilities to be able to manufacture the Johnson & Johnson vaccine, one of the officials said. The company will be able to start the fill-finish process in about two months, this official said, and it will take longer than that to ramp up actual production of the vaccine itself.

https://www.nytimes.com/live/2021/03/02/world/covid-19-coronavirus#under-a-white...

Sex Differences in Immune Responses to Viral Infection
Catherine Offord | Mar 1, 2021

Stronger interferon production, greater T cell activation, and increased susceptibility to autoimmunity are just some of the ways that females seem to differ from males...

https://www.the-scientist.com/features/sex-differences-in-immune-responses-to-vi...

To Beat COVID, We May Need a Good Shot in the Nose
Daniel P. Oran, Eric Topol on March 1, 2021

Intranasal vaccines might stop the spread of the coronavirus more effectively than needles in arms

...Although injected vaccines do reduce symptomatic COVID cases, and prevent a lot of severe illness, they may still allow for asymptomatic infection. A person might feel fine, but actually harbor the virus and be able to pass it on to others. The reason is that the coronavirus can temporarily take up residence in the mucosa—the moist, mucus-secreting surfaces of the nose and throat that serve as our first line of defense against inhaled viruses. Research with laboratory animals suggests that a coronavirus infection can linger in the nose even after it has been vanquished in the lungs. That means it might be possible to spread the coronavirus after vaccination.

...In a study using laboratory animals, an experimental intranasal vaccine created by scientists at the Washington University School of Medicine induced a powerful immune response in both the mucosa and the rest of the body, almost entirely preventing infection.

...Intranasal vaccines have some practical advantages, too. Unlike an injection, a nasal spray is painless. The absence of a needle might allay the concerns of those who are now hesitant about vaccination. An intranasal vaccine can also be self-administered at home, with minimal instruction. And some of the intranasal vaccines now being tested require no refrigeration, making them easy to transport and store, especially in low-resource countries...

https://www.scientificamerican.com/article/to-beat-covid-we-may-need-a-good-shot...

Much of the world is seeing coronavirus cases fall. But Brazil’s outbreak is worse than ever.
Terrence McCoy | March 1, 2021

...While much of the world is using restrictions and vaccines to try to tame the coronavirus, Brazil’s outbreak is worse than it has ever been. Deaths have hit a new high, averaging 1,208 per day over the past week. Public hospital occupancy is peaking. Health systems in more than half the country’s 26 states are at or near capacity. And a highly transmissive and potentially more dangerous variant is spreading nationwide.

From the earliest days, the severity of Brazil’s outbreak has set the country apart from its peers. Under the chaotic leadership of President Jair Bolsonaro, the country has been consumed by internal divisions, set upon by medical quacks, unable to pull itself out from the abyss. More than a quarter million Brazilians are now dead, a toll surpassed only by the United States. The country’s vaccination campaign is bogging down in shortages and delays.

...Lígia Bahia, a public health professor at the Federal University of Rio de Janeiro, said the tragedy of Brazil has been the triumph of doubt over reason, politics over science...But she said there was time for the government and the people to act. Brazil once had one of the strongest vaccination programs in the developing world. It has the capacity to vaccinate millions of people every day. A population largely willing to receive it. And the vaccine is here.

Bahia worries, however, about what the coming weeks will bring. “It will get worse, certainly...There will be no letup.”

https://www.washingtonpost.com/world/the_americas/coronavirus-brazil-vaccine-var...

What Happens When People Get Infected With 2 Strains of COVID at Once?
MAITREYI SHIVKUMAR | 4 MARCH 2021

Scientists in Brazil recently reported that two people were simultaneously infected with two different variants of SARS-CoV-2, the virus that causes COVID-19...seemed to have no effect on the severity of patients' illness, and both recovered without needing to be hospitalized...study is yet to be published in a scientific journal

Viruses...constantly mutat(e) and creat(e) new variants with every cycle of replication. Selective pressures in the host, such as our immune response, also drive these adaptations. Most...won't have a significant effect on the virus. But ones that give an advantage to the virus – for example, by increasing its ability to replicate or evade the immune system – are cause for concern and need to be closely monitored.

...RNA viruses, such as influenza and hepatitis C, generate a relatively large number of errors each time they replicate. This creates a "quasi-species" of the virus population, rather like a swarm of viruses, each with related but non-identical sequences. Interactions with the host cells and immune system determine the relative frequencies of the individual variants, and these coexisting variants may affect how the disease progresses or how well treatments work.

Compared with other RNA viruses, coronaviruses have lower mutation rates. This is because they are equipped with a proofreading mechanism that can correct some of the errors that occur during replication.

...multiple variants in a person could be the result of co-infection by the different variants, or the generation of mutations within the patient after the initial infection. One way to discriminate these two scenarios is by comparing the sequences of the variants circulating in the population with those in the patient.

In the Brazilian study mentioned above, the variants identified corresponded to different lineages that had been previously detected in the population, implying co-infection by the two variants.

...co-infection has opened concerns of SARS-CoV-2 acquiring new mutations even more rapidly...because coronaviruses can also undergo large changes in their genetic sequence by a process called recombination. When two viruses infect the same cell, they can swap large parts of their genomes with each other and create completely new sequences.

...Evidence of recombination has been found both in the laboratory and in a patient infected with SARS-CoV-2, suggesting that this could drive the generation of new variants. In fact, the ability of SARS-CoV-2 to infect human cells is proposed to have developed via recombination of the spike protein between closely related animal coronaviruses.

...this requires the two viruses to infect the same cell...

https://www.sciencealert.com/people-are-getting-infected-with-different-covid-va...

NACI (Cdn National Advisory Committee on Immunization): second doses of COVID-19 vaccines can be given up to 4 months after first
Rachel Aiello | March 3, 2021
https://www.ctvnews.ca/health/coronavirus/second-doses-of-covid-19-vaccines-can-...

___________________________________________________

David Fisman @DFisman | 8:26 AM · Mar 3, 2021
(epidemiologist, U of Toronto, prov task force, elementary school teacher advisor--google him)

On the issue of increasing the dosing interval for mRNA vaccines (limiting this to mRNA vaccines), we:
a. Have good observational evidence now that there is at least short term protection after first dose.
That’s also there in the RCT (randomized controlled trial) though of course that effect gets stepped on by 2nd dose in rct.

b. The seroresponse to mRNA vaccines is impressive. That’s not 1:1 with protection but we use it because it’s a good surrogate

c. We know that even passive administration of antibody such as hep A immune globulin, protects for 2 months. And that’s a passive protection without the immune activation generated by immunization. So even passive vax would be good for a couple of months.

d. The dramatic increase in herd protection engendered by suddenly doubling (and using) our mRNA vaccine supplies is going to be a major force multiplier for Canada.

e. Empirically, we see that provinces that have pushed ahead with first dose to as many as possible (bc, Qc) have marked declines in mortality. They don’t seem to have lost anything and may have gained.

f. Proceeding based on best available understanding in a timely manner is what the precautionary principle is all about. Am I certain that this is the correct course of action absent RCT? No.

Do I think it’s reasonable, prudent, and readily justifiable, based on the best available data, as of right now, and based on my best judgement as someone studying infectious diseases for the past 25 years?

Yes, I really do

Do I have a high level of confidence in NACI to weigh the pros and cons on this issue before making their decision public?

Yes, I really do.

Hope that’s helpful.

Move over, Asian Americans? BE KIND!

Most coronavirus deaths have occurred in countries where majority of adults are overweight
Erin Cunningham and Jennifer Hassan | March 4, 2021

...The report, by the World Obesity Federation, found that 88 percent of deaths due to covid-19 in the first year of the pandemic were in countries where more than half of the population is classified as overweight, which it defines as having a body mass index (BMI) above 25. Obesity, generally defined as BMI above 30, is associated with particularly severe outcomes.

Among the nations with overweight populations above the 50 percent threshold were also those with some of the largest proportions of coronavirus deaths — including countries such as Britain, Italy and the United States. Some 2.5 million people have died around the world of covid-19, more than 517,000 of which were in the United States...

https://www.washingtonpost.com/world/2021/03/04/coronavirus-overweight-global-re...

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WORLD OBESITY
COVID-19 and Obesity: The 2021 Atlas
The cost of not addressing the global obesity crisis
March 2021
227 p
https://www.worldobesityday.org/assets/downloads/COVID-19-and-Obesity-The-2021-A...

FOREWORD
Welcome to our review of the links between COVID-19 and bodyweight, and the steps we need to take to avert future crises.

As we show in this report, increased bodyweight is the second greatest predictor of hospitalisation and a high risk of death for people suffering from COVID-19. Only old age rates as a higher risk factor. The unprecedented economic costs of COVID-19 are largely due to the measures taken to avoid the excess hospitalisation and need for treatment of the disease. Reducing one major risk factor, overweight, would have resulted in far less stress on health services and reduced the need to protect those services from being overwhelmed.

We show that in those countries where overweight affects only a minority of the adult population, the rates of death from COVID-19 are typically less than one tenth the levels found in countries where overweight affects the majority of adults.

We also show that the drivers of overweight – especially high levels of consumption of processed foods – are associated with mortality from COVID-19.

Lastly, we show that COVID-19 is not a special case: a number of other respiratory viruses lead to more severe consequences in people living with excess bodyweight, giving good reasons to expect the next pandemic to have similar effects.

For these reasons we need to recognise overweight as a major risk factor for infectious diseases including respiratory viruses. To prevent pandemic health crises in future requires action now: we call on all readers to support the World Obesity Federation’s call for stronger, more resilient economies that prioritise investment in people’s health.

CONTENTS
Executive summary
Roots: A Call for Action.
Obesity and the response to COVID-19

COVID-19 and the Obesity: The Evidence
1. Is overweight associated with the severity of COVID-19 and the need for health services?
2. Is this link between COVID-19 and overweight found across the globe?
3. Is this correlation between population overweight and COVID-19 mortality due to a higher proportion of older people being found in countries where overweight is more common?
4. Is this correlation between population overweight and COVID-19 mortality due to wealthier countries having both a higher level of COVID-19 deaths and also a higher prevalence of overweight?
5. Is the correlation between population overweight and COVID-19 mortality due to better reporting of deaths in countries with higher levels of overweight?
6. Is there a threshold proportion of the population being overweight that predicts a high COVID-19 mortality rate?207.
7. Are the drivers of overweight also linked to COVID-19?
8. What are the costs of COVID-19?239.
9. ... and how much of these costs could be due to overweight?
10. If the COVID-19 vaccine is successful, can we relax?

Global Maps
1. COVID-19 mortality
2. Prevalence of overweight in adults
3. Percentage of adults aged over 65 years
4. Gross Domestic Product per capita
5. Healthy adult life expectancy
6. Percentage adults with insufficient physical activity
7. Consumption of pulses
8. Consumption of starchy root vegetables
9. Consumption of animal fats
10. Consumption of vegetable oils
11. Consumption of sugars
12. Consumption of sugar-sweetened beverages

Country Reports

Appendix
Data sources
References

Eric Topol @EricTopol | 11:18 AM · Mar 4, 2021
Covid and the eyes
52 of 91 hospitalized patients (57%) with covid were PCR positive by conjunctival swabs

Image-abstract ( https://twitter.com/EricTopol/status/1367509663785259010/photo/1 )
Image-photos, sampling inside eyelid ( https://twitter.com/EricTopol/status/1367509663785259010/photo/2 )

Claudio Azzolini et al. 2021. SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy. JAMA Ophthalmol. Published online March 4, 2021. doi:10.1001/jamaophthalmol.2020.5464 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2777178

Key Points
Question
What is the qualitative and quantitative presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the ocular surface in patients with coronavirus disease 2019 (COVID-19) hospitalized in intensive care units at a university hospital in Lombardy, Italy?

Findings
Using reverse transcription–polymerase chain reaction assay, this study found that SARS-CoV-2 was present on the ocular surface in 52 of 91 patients with COVID-19 (57.1%). The virus may also be detected on ocular surfaces in patients with COVID-19 when the nasopharyngeal swab is negative.

Meaning
These results suggest that SARS-CoV-2 may diffuse from ocular surfaces to the body.

Abstract
...Conclusions and Relevance
In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

Eric Topol @EricTopol | 11:27 AM · Mar 4, 2021:
The impact of vaccines and comparison with respect to efficacy TheEconomist

Image-Pfizer ( https://twitter.com/EricTopol/status/1367511995746897921/photo/1 )
Image-Pfizer, Moderna, J&J, Astrazeneca ( https://twitter.com/EricTopol/status/1367511995746897921/photo/2 )

https://economist.com/graphic-detail/2021/03/06/new-data-show-that-leading-covid...

Amazing. While Texas and Mississippi are opening and dispensing with masks, a region of Ontario, already in the green zone with very few cases (but a few variants of concern such as B.117 cropping up--they screen), has taken week long action to discourage U students especially from celebrating St Patrick's Day with their usual vigour, e.g., street parties, pub crawls.

Class Order: https://www.kflaph.ca/Modules/News/index.aspx?feedId=f2a4adbc-2838-4b5d-a47c-bd9...

Explanatory Video: https://www.youtube.com/watch?v=ewLrntrIpGQ&feature=youtu.be

Medical News Today: "A new study suggests that among people hospitalized for COVID-19, blood levels of five proteins are higher in those who will go on to require critical care...If replicated, the findings could lead to new tests and treatments for severe COVID-19.

---------------------------------------------------------------
Matthew L. Meizlish et al. 2021. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Adv (2021) 5 (5): 1164–1177. https://doi.org/10.1182/bloodadvances.2020003568 https://ashpublications.org/bloodadvances/article/5/5/1164/475293/A-neutrophil-a...

Key Points
Markers of neutrophil activation (RETN, LCN2, HGF, IL-8, G-CSF) are among the most potent discriminators of critical illness in COVID-19.

Evidence of neutrophil activation precedes the onset of critical illness and predicts mortality in COVID-19.

Visual Abstract...

Abstract
Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.

COVID-19 vaccines touchdown in Sudan and Rwanda (UN News)

In a boost for equitable distribution in Africa, 800,000 doses of the AstraZeneca shots touched down in Khartoum... to receive the vaccine... Meanwhile, Rwanda also received 240,000 doses from the same manufacturer and anticipates 102,000 more shots from Pfizer-BioNTech mRNA, which is set to arrive on Wednesday...

The ins and outs of Kenya’s COVID-19 vaccine rollout plan
Catherine Kyobutungi | March 3, 2021

With the arrival* of vaccines in the country, Kenya is set to begin its COVID-19 vaccination roll-out. Catherine Kyobutungi, Executive Director of the African Population and Health Research Center, provides some insights into the country’s COVID-19 vaccine strategy and the inclusion of private companies in vaccination programmes.

A. What’s the rollout plan?
Regulatory preparedness
Planning and coordination
Funding

Target populations and vaccination strategies:
vaccine rollout will be done in three phases. The first involves 1.25 million people and runs between now and June 2021. Phase two will run between July 2021 and June 2022, targeting the most vulnerable, including the elderly and those above 18 years with comorbidities. It targets 9.76 million people. Phase three focuses on other vulnerable groups of people of 18 years and above in congregations, hospitality and the tourism industry. The phase will run between July 2022 and June 2023. It targets 4.9 million people.

All the phases are based on vaccine availability, storage requirements and administration sites that can reach prioritised populations. In phase one, as much as possible will be done through hospitals.

Supply chain management
Human resources management and training
Monitoring and evaluation system

B. What vaccines have been procured?

At the time of developing the plan, only three vaccines had been authorised for use by the WHO. These are the Pfizer BioNTech, Moderna, and the Oxford/AstraZeneca. Since then other vaccines have been authorised by stringent regulatory authorities elsewhere. This means that their approval for use in Kenya will eventually be expedited.

Kenya’s first rollout, of about one million doses, will be of the AstraZeneca-Oxford vaccine.

C. What’s the role of private companies?
What are the advantages of allowing this?
What are the drawbacks and challenges?

https://theconversation.com/the-ins-and-outs-of-kenyas-covid-19-vaccine-rollout-...

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Kenya to begin Covid-19 vaccination drive Friday
Christine Muchira | March 4, 2021

Kenya will start the vaccination drive against Covid-19 Friday at Kenyatta National Hospital following the flagging off of the vaccines at the central vaccine storage site in Kitengela.

According to Health Cabinet Secretary Mutahi Kagwe, the process is being rolled out in all the 47 counties, starting with frontline workers, teachers, security personnel and those over 58 years.

The country received the first batch of 1.02 million doses under the Vaccines Global Access (COVAX) program on Tuesday evening aboard a Qatar Airways flight QR1341.

The consignment was received by top government officials led by Health Cabinet Secretary Mutahi Kagwe, Transport CS James Macharia and CS Margaret Kobia.

Kenya is among the first countries on the continent to receive and commence a COVID-19 vaccination program.

Since the arrival on Tuesday night, the vaccine consignment has been kept at the main central storage facility in Kitengela, Kajiado county.

https://www.kbc.co.ke/covid-19-vaccination-process-begins-friday/

>120 margd:

Thanks - for some reason I hadn't seen that news locally. I've already contacted a couple of doctors to find out how, when and if an over-58 year old can get vaccinated.

>121 John5918: I was surprised at "over 58". Kenya sure sets a low bar for geezers! :D

Ontario pilot program starts next week with over-80s. Michigan started with over-75s ~ January when few vaccines. Chaotic, it seemed to me. When more vaccines and over-65s were welcomed, friends in neighboring county walked in, but with three large hospitals (= lots of healthcare workers) in our city, some very elderly, compromised people had to wait. Now Michigan has offered the vaccine to over-50s with conditions, but it wasn't clear to me how people are supposed to prove their 'conditions'.

Do plan a couple of light days after your vaccination(s). I could still function after my Pfizer shot Tuesday, but was fatigued and achy, especially the first 24 hrs. (= small price for peace of mind!)
_______________________________________________________

Sounds like the kids might be facing a bit more disease--at least in Montreal... https://montrealgazette.com/news/local-news/rare-post-covid-19-syndrome-in-child...

Laura A. Vella et al. 2021. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19 Science Immunology. 02 Mar 2021: Vol. 6, Issue 57, eabf7570 DOI: 10.1126/sciimmunol.abf7570 https://immunology.sciencemag.org/content/6/57/eabf7570

Abstract

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells* that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells* in the clinical presentation and trajectory of MIS-C...

Abstract with Eric Topol's highlights: https://twitter.com/EricTopol/status/1367308664785149957/photo/2

* Cytotoxic T cells
CD8+ (cytotoxic) T cells, like CD4+ Helper T cells, are generated in the thymus and express the T-cell receptor. ... CD8+ T cells (often called cytotoxic T lymphocytes, or CTLs) are very important for immune defence against intracellular pathogens, including viruses and bacteria, and for tumour surveillance. https://www.immunology.org/public-information/bitesized-immunology/cells/cd8-t-c...

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In earlier study (I'll link tomorrow), mother's antibodies (IgG) could reach the fetus, but because no IgM in womb, researchers thought the virus could not. Below, it appears a fetus was exposed at ~31 weeks gestation. Newborns are especially vulnerable for their first two months, according to earlier article:

Article with Eric Topol's highlights: https://twitter.com/EricTopol/status/1367308664785149957/photo/1

Mahesh Kappanayil et al. 2021. Multisystem inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: a case report. The Lancet (March 03, 2021) DOI:https://doi.org/10.1016/S2352-4642(21)00055-9
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00055-9/fullt...

>122 margd: I was surprised at "over 58". Kenya sure sets a low bar for geezers!

In a country where the average life expectancy is only about 66 (compared to 78 in the USA and 81 in the EU), I suppose 58 seems reasonable. When they were setting restrictions on public gatherings last year 58 was also the age at which we were advised not to attend church services.

Australia asks E.U. to stop blocking Covid vaccines after Italy bans AstraZeneca exports
Italy banned a shipment of more than a quarter-million doses of AstraZeneca's Covid-19 shots from leaving the 27-nation bloc for Australia.
AP | March 5, 2021

...(Australian) Health Minister Greg Hunt has asked the European Union's executive arm, the European Commission, to review the Italian decision.

The shipment ban was the latest development in the dispute between the E.U. and AstraZeneca over delays in deliveries.

Faced with shortages of doses during the early stages of the vaccine campaign that started in late December in the bloc, the E.U. issued an export control system for Covid-19 vaccines in late January, forcing companies to respect their contractual obligations to the bloc before commercial exports can be approved.

The E.U. has been specifically angry with AstraZeneca because it is delivering far fewer doses to the bloc than it had promised. Of the initial order for 80 million doses to the E.U. in the first quarter, the company will be struggling to deliver half that quantity.

The E.U. thought it had made excellent preparations for the rollout of vaccines. With its 450 million people, the E.U. has signed deals for six different vaccines. In total, it has ordered up to 400 million doses of the AstraZeneca vaccine and sealed agreements with other companies for more than 2 billion shots.

But only 33 million doses have been given so far, and only 11 million Europeans have been fully vaccinated. Despite the current difficulties, the E.U.'s goal remains to vaccinate 70% of the adult population in the bloc by the end of summer.

https://www.nbcnews.com/news/world/australia-asks-e-u-stop-blocking-covid-vaccin...

B117 in kids:

Eric Feigl-Ding (epidemiologist economist) @DrEricDing | 2:51 AM · Mar 5, 2021
For images and links, go to https://twitter.com/DrEricDing/status/1367744596504158208

HIGHEST IN KIDS—newest French data this week shows #B117 is the most dominant & has the highest prevalence in kids ages 0-9. This matches data from United Kingdom (where B117 nearly completely dominant) showing highest #COVID19 incidence in kids. This also matches kids surge in Italy & Israel

2) Here is the newest UK data from England showing the highest positivity of #COVID19 in kids for the first time (this wasn’t true in the past). This again matches warnings we see elsewhere in the world. Leaders of each country have to acknowledge this.

KIDS ages 5-12 now the *highest positive prevalence age group* for #COVID19 in England in February (not previously in Jan), despite lockdown.
Higher odds of COVID for workers in: healthcare, transport, & education, school, nursery or childcare.
https://spiral.imperial.ac.uk/handle/10044/1/86343

3) and my god, #B117 has now pretty much dominated half of France

4) We know #B117 is more contagious by 40-60%. Do we see it throughout France? YES!! Areas with higher B117 #SARSCoV2 proportion, higher the incidence of #COVID19.

5) there is definitely something going on with the #B117 variant (where it is fully dominant in United Kingdom) and kids. This new weird pediatric trend has been now seen in Italy, Israel, Denmark, and now France too. Italy’s leadership sounded the alarms recently about B117 & kids.

KIDS EPIDEMIC in Italy · Mar 2
—#B117 variant among Italy's infected schoolchildren and is helping to fuel a “robust” uptick in the curve of #COVID19–with higher transmission rates "among the youngest age group” of the population.
https://finance.yahoo.com/news/virus-variant-races-italy-especially-210020179.ht...

6) New studies indeed confirm that “kids are the drivers of transmission”. Asymptomatic kids carry just as much viral load as adults...

”Children may be **drivers of #SARSCoV2 transmission** in the general population at the same level as adults”, says new Spain
study. While viral load was significantly higher in symptomatic than in asymptomatic adults—but in children, they were equal!
https://medrxiv.org/content/10.1101/2021.03.03.21252814v1

7) Kids are more often silent asymptomatic spreaders and much less likely detected too. Thus what we are finding for highest in kids is just tip of the iceberg. (New CDC-study in Mississippi found actual number of kids infected with #COVID19 was much higher than testing reported.)

8) Let’s flip it around... if a family has a lot of kids, are the adults more likely infected??? YES... and more kids in household, the higher the risk. (Danish study)

9) And don’t forget that #B117 is not only more contagious, new data from Denmark CDC shows it is also more severe. Danes have the best B117 data because they sequence everyone. Read this thread and the table below.

>91 margd: contd.

Long COVID patients say they feel better after getting vaccinated
The shots might help people with chronic symptoms
By Nicole Wetsman Mar 2, 2021

...Some patient surveys are trying to get an early read on how widespread improvement is. Director Gez Medinger, who covers long COVID on his YouTube channel, surveyed nearly 500 people in various long-hauler support groups on Facebook. Around a third of people surveyed said that they felt slightly or entirely better when they were at least two weeks out from vaccination.

Dozens of people who responded to a poll in the Facebook group for Survivor Corps said that their symptoms improved slightly or went away almost completely. “We were really concerned that people were going to have bad reaction. It never occurred to us that they would actually improve,” Diana Berrent, founder of the COVID-19 survivors and long-haulers group Survivor Corps.

...The early reports are a good push for people with chronic COVID-19 symptoms to get vaccinated, (Daniel Griffin, an infectious diseases clinician and researcher at Columbia University) says. “It doesn’t look harmful, and it may be therapeutic. I think it’s encouraging for people with long COVID to get signed up as soon as they can.”

https://www.theverge.com/2021/3/2/22308965/covid-vaccine-shots-symptoms-improve-...

A 'me first' approach to vaccination won't defeat Covid (Guardian) by Tedros Adhanom Ghebreyesus

of the 225m vaccine doses that have been administered so far, the vast majority have been in a handful of rich and vaccine-producing countries, while most low- and middle-income countries watch and wait. A me-first approach might serve short-term political interests, but it is self-defeating and will lead to a protracted recovery, with trade and travel continuing to suffer...

Covid-19 vaccine: Senegal, Kenya, Sudan, Rwanda, Gambia get the shot (Logistics Update Africa)

UNICEF has accelerated the delivery of Covid-19 vaccines to Africa with the recent distribution to Senegal, Kenya, Sudan, and Gambia...

FDA News Release
Coronavirus (COVID-19) Update: FDA Authorizes Adaptive Biotechnologies T-Detect COVID Test
March 05, 2021

Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the T-Detect COVID Test developed by Adaptive Biotechnologies. The T-Detect COVID Test is a next generation sequencing based (NGS) test to aid in identifying individuals with an adaptive T cell immune response to SARS-CoV-2, indicating recent or prior infection with SARS-CoV-2.

“Today’s authorization further underscores the FDA’s commitment to innovation in test development,” said Jeff Shuren, M.D., J.D., director of FDA’s Center for Devices and Radiological Health. “The T-Detect COVID Test is a novel technology that assesses the T cell immune response to COVID-19. Information and scientific data that deepen our understanding of SARS-CoV-2 remain important keys to get ahead of this global pandemic.”...

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-...

Gery P. Guy Jr. et al. 2021.Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates — United States, March 1–December 31, 2020. CDC Morbidity and Mortality Weekly Report (MMWR) / March 5, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e3.htm

...Mandating masks was associated with a decrease in daily COVID-19 case and death growth rates within 20 days of implementation.

...Allowing on-premises restaurant dining was associated with an increase in daily COVID-19 case growth rates 41–100 days after implementation and an increase in daily death growth rates 61–100 days after implementation...

U.K. Variant Is Spreading Fast in U.S., Even as Overall Cases Level Off
Lauren Leatherby and Scott Reinhard | March 6, 2021

As U.S. coronavirus cases remain at a low not seen since October, a more contagious variant first reported in the United Kingdom has likely grown to account for more than 20 percent of new U.S. cases as of this week, according to an analysis of data from Helix, a lab testing company.

There is not yet enough genomic sequencing — the process required to screen positive coronavirus samples for variants — to be certain of how widely that variant, known as B.1.1.7, is spreading. But data suggests its share of total cases is growing at a trajectory similar to that seen in countries where it has fueled surges...

Graph, incidence of B.1.1.7. v original in US, FL, TX, CA, as captured by
https://twitter.com/EricTopol/status/1368220747521425418/photo/1

https://www.nytimes.com/interactive/2021/03/06/us/coronavirus-variant-sequencing...

>123 John5918: The US lost a full year of life expectancy (from 78.8 to 77.8) in 2020. Blacks and Hispanics bore the worst of it: 2 to 3 years lost... Hopefully, other people will fare better.

The short-term, middle-term, and long-term future of the coronavirus
Andrew Joseph and Helen Branswell | March 4, 2021

...many predict that (the coronavirus) will become a seasonal pathogen that won’t be much more than a nuisance for most of us who have been vaccinated or previously exposed to it...the transition to a mild endemic virus is unlikely to be a straight line. Some infectious disease researchers envision a healthier summer — with low circulation of the virus and more people vaccinated — but a more tenuous fall. Other factors, like how long protection provided by vaccines will last, what percentage of people gets them, and whether variants of the virus sap the strength of vaccines, will determine the outcome...there won’t be a single moment, like jolting awake from a nightmare...people will once again become vulnerable, either because their immunity wanes or the pathogen evolves in ways that allow it to infect even people who have protection against earlier strains. Newborns will also add to the pool of susceptibles. “Susceptible replenishment,” as it’s known, is why some experts expect seasonal waves going forward...Years from now, SARS-CoV-2 could join the ranks of OC43, 229E, NL63, and HKU1— the four endemic, seasonal coronaviruses that cause a chunk of common colds every year. Essentially, our immune systems — primed by vaccines, boosters, and previous encounters with the coronavirus — will be ready to knock back SARS-2 when we see it again, potentially blocking an infection or leading to one that causes no symptoms or maybe just the sniffles...having SARS-2 join the ranks of flu viruses would be a most unwelcome outcome. While most people don’t see the flu as an existential threat, it still kills...

https://www.statnews.com/2021/03/04/the-short-term-middle-term-and-long-term-fut...
_________________________________________________________

Comparing the Covid-19 vaccines developed by Pfizer, Moderna, and Johnson & Johnson
Helen Branswell | Feb. 2, 2021

https://www.statnews.com/2021/02/02/comparing-the-covid-19-vaccines-developed-by...

"...the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses..."

Eric Topol @EricTopol | 11:57 AM · Mar 7, 2021:
What happens when people with prior covid get vaccinated with 1st and 2nd dose compared with those without prior infections?

https://medrxiv.org/content/10.1101/2021.03.03.21252872v1 *
No increase in circulating antibodies or antigen-specific memory B-cells from 2nd dose.
More support for 1-dose for prior covid

Image from the preprint ( https://twitter.com/EricTopol/status/1368606826221039619/photo/1 )
E. John Wherry and 2 others

------------------------------------------------------

Also, "...the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses..."

Rishi R Goel et al. 2021. Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naive and Recovered Individuals Following mRNA Vaccination. medRxiv (March 6, 2021)
doi: https://doi.org/10.1101/2021.03.03.21252872 https://www.medrxiv.org/content/10.1101/2021.03.03.21252872v1

This article is a preprint and has not been certified by peer review

Abstract
Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naive subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naive subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naive and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naive individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naive individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.

Not advisable to open up / terminate mask mandate, Governor Neanderthal, er, Abbott?
(Even if you need a diversion from power fiasco...)

"...genome sequencing program involving 20,453 virus specimens from COVID-19 patients dating from March 2020, we report identification of all important SARS-CoV-2 variants among Houston Methodist Hospital patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency in the population, they are geographically widespread.

S. Wesley Long et al. 2021. Sequence Analysis of 20,453 SARS-CoV-2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern. MedRxiv March 2,2021. doi: https://doi.org/10.1101/2021.02.26.21252227 https://www.medrxiv.org/content/10.1101/2021.02.26.21252227v1

This article is a preprint and has not been peer-reviewed

Abstract
Since the beginning of the SARS-CoV-2 pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several “variants of concern” emerged globally, including the UK variant (B.1.1.7), South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California “variants of interest” (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility capacity. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. Based on our extensive genome sequencing program involving 20,453 virus specimens from COVID-19 patients dating from March 2020, we report identification of all important SARS-CoV-2 variants among Houston Methodist Hospital patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency in the population, they are geographically widespread. Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination. This information is critical for medical and public health efforts to effectively address and mitigate this global crisis.

Excerpt (table) -- https://twitter.com/DrEricDing/status/1368430097267580930/photo/1

Transcript of fluvoxamine story on Sunday night's CBS TV news program "60 Minutes"
(mentioned briefly in Scientific American article, #96 in thread 16):

Finding a possible early treatment for COVID-19 in a 40-year-old antidepressant
Sharyn Alfonsi | March 7, 2021
https://www.cbsnews.com/amp/news/fluvoxamine-antidepressant-drug-covid-treatment...
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Eric J. Lenze et al. 2021. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19A Randomized Clinical Trial. JAMA (Preliminary Communication, November 12, 2020); 324(22):2292-2300. doi:10.1001/jama.2020.22760 https://jamanetwork.com/journals/jama/fullarticle/2773108

...In this randomized trial that included 152 adult outpatients with confirmed COVID-19 and symptom onset within 7 days, clinical deterioration occurred in 0 patients treated with fluvoxamine vs 6 (8.3%) patients treated with placebo over 15 days, a difference that was statistically significant...
------------------------------------------------------------------
With hydroxychloroquine in mind, Editor's Note:

Christopher W. Seymour et al. 2020. COVID-19 Infection—Preventing Clinical Deterioration (Editor's Note). JAMA. November 12, 2020;324(22):2300. doi:10.1001/jama.2020.21720 https://jamanetwork.com/journals/jama/fullarticle/2773107

...This study by Lenze and colleagues3 presents only preliminary information, and requires confirmation in larger trials. But at the same time, it is a double-blind, placebo-controlled, randomized clinical trial, which is generally considered a design that minimizes bias and can support causal inference...

Growing Share of Americans Say They Plan To Get a COVID-19 Vaccine – or Already Have
77% think vaccinations will benefit U.S. economy
Cary Funk and Alec Tyson | March 5, 2021

...a new Pew Research survey finds public intent to get vaccinated is on the rise.

Overall, 19% of adults say they have already received at least one dose of a coronavirus vaccine. Another 50% say they definitely or probably plan to get vaccinated. Taken together, 69% of the public intends to get a vaccine – or already has – up significantly from 60% who said they planned to get vaccinated in November...Black Americans...older adults...

People with lower income levels continue to be less inclined than those with higher incomes to get a vaccine...14% of lower-income adults say they have gotten at least one dose of a vaccine, compared with 20% of middle-income adults and 27% of upper-income adults.

A smaller majority of women (66%) than men (72%) intend to get a vaccine or have already received at least one dose...more likely than men to cite concerns about the rapid pace of vaccine development and a lack of information about how well they work as major reasons why they don’t plan to get a vaccine.

Partisan differences...Democrats are now 27 percentage points more likely than Republicans to say they plan to get, or have already received, a coronavirus vaccine (83% to 56%). This gap is wider than those seen at multiple points in 2020.

...Those who do not currently plan to get a vaccine (30% of the public) list a range of reasons why. Majorities cite concerns about side effects (72%), a sense that vaccines were developed and tested too quickly (67%) and a desire to know more about how well they work (61%) as major reasons why they do not intend to get vaccinated...

https://www.pewresearch.org/science/2021/03/05/growing-share-of-americans-say-th...

Rockefeller Foundation:

Our report lays out a new plan for the urgent amplification of national genomic surveillance efforts and outlines a six-part strategy to enable rapid detection and control of emerging SARS-CoV-2 variants. The threat of new and existing dangerous variants requires urgent action. Together, our report and accompanying implementation framework provide a blueprint for mobilizing an array of resources, stakeholders, and strategies to reduce the spread of these concerning variants in the short-term, and control future pandemics in the long-term...

https://www.rockefellerfoundation.org/report/accelerating-national-genomic-surve...

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Accelerating National Genomic Surveillance
Rockefeller Foundation | March 2021
14 p

...Action Plan to Accelerate Genomic Surveillance in the US

1. Build a viral defense system
Create sentinel sites around the country that detect a new virus or new variant as soon as it appears. Set basic proto-cols for specimen and data collection, sequencing, and structural genotypic and functional phenotypic analysis. Address barriers that prevent the diverse set of players from effectively cooperating. Connect this system to a global system that shares data and analytic outcomes so threats can be detected anywhere in the world.

2. Be diverse and deeply human
Black, Hispanic, and Native American. The old, those with chronic conditions, and the immunocompromised. Covid-19 has hit such groups particularly hard, and tracing its uneven effects is vital to an equitable recovery. Ensuring genomic surveillance benefits all Americans by analyzing samples representative of all Americans. Also, ensuring sequencing of highly atypical clinical cases.

3. Connect the dots
The Tower of Babel that characterizes the nation’s electronic medical records cannot be allowed to curse this effort. Critical epidemiological and clinical data is often impossible to access and usually not connected to viral genomic data. A national standard for the col-lection, aggregation, and sharing of risk-related medical information that safeguards privacy and adheres to the law must be created. A network that links these disparate datasets is needed.

4. Provide more to do more
Expanding genomic sequencing will require more people, sequencing equipment, computers, reagents, sample storage, and a host of other supplies. This cannot be done on the usual public health shoestring. Although the Biden administration’s $200 million down payment is a good start, much more support is required to establish, expand, and sustain a system designed to stay in front of a rapidly mutating and spreading virus.

5. Build new analytic tools and make them visual
New software tools for analyzing genomic data that are easy-to-use and scalable are urgently needed. Visualization tools must be built and distributed to help state and local officials and eventually national officials around the world to understand and explain viral spread and threats.

6. Rapidly assess the threat posed by new variants
When significant mutations occur, there is a need to understand their biology at the molecular level and determine if these changes in the virus make it more transmissible, more virulent, or impact the effectiveness of vaccines and therapeutics. This research requires storage of more samples and improved access to viral isolates...

https://www.rockefellerfoundation.org/wp-content/uploads/2021/03/The-Rockefeller...

Statin users 50% less likely to die in hospital from severe COVID-19
Mary Cooke | March 6, 2021

A new study suggests that taking statins may help reduce the risk of dying from severe COVID-19.

In the study, people who regularly took statins before they developed COVID-19 were roughly 50% less likely to die in the hospital than people who did not.

Statin usage also seemed to reduce patient levels of C-reactive protein, a marker of inflammation.

If further studies support these findings, this could provide a cost-effective, widely-available, low-risk treatment option for COVID-19...

https://www.medicalnewstoday.com/articles/statin-users-50-less-likely-to-die-in-...
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Aakriti Gupta et al. 2021. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nature Communications volume 12, Article number: 1325 (26 Feb 2021) https://www.nature.com/articles/s41467-021-21553-1

The 1st prospective study (preprint) to determine risk of developing #LongCovid (at least that I've seen)
https://medrxiv.org/content/10.1101/2021.03.08.21253124v1 *
Notable risk factors among 146 patients were
female sex (lower 95% CI .96),
WHO severity, and
(lower) peak IgG antibody titer to spike protein

Image ( https://twitter.com/EricTopol/status/1368998965174169604/photo/1 )

- Eric Topol @EricTopol | 1:56 PM · Mar 8, 2021

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Javier Garcia-Abellan et al. 2021. Long-term clinical, virological and immunological outcomes in patients hospitalized for COVID-19: antibody response predicts long COVID. MedRxiv (March 08, 2021) doi: https://doi.org/10.1101/2021.03.08.21253124 https://www.medrxiv.org/content/10.1101/2021.03.08.21253124v1

This article is a preprint and has not been certified by peer review

Abstract
Objective: Long-term data following SARS-CoV-2 infection are limited. We aimed to characterize the medium and long-term clinical, virological, and immunological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.

Methods: Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2 and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID19-symptom-questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.

Results: Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2-months and 6-months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct=38) and 3% (median Ct=36) patients at 2-months and 6-months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR 95%CI) were lower peak S-IgG (0.80 0.66-0.94) and higher WHO-severity-score (2.57 1.20-5.86); 6-month predictors were lower peak S-IgG (0.89 0.79-0.99) and female sex (2.41 1.20-4.82); no association was found with prolonged viral shedding.

Conclusions: Late clinical events and persistent symptoms in the medium and long term occurred in a significant proportion of patients hospitalized for COVID-19. Gender, severity of illness and weaker antibody responses, but not viral shedding, were associated with long-COVID.

"...pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Lockdown halved infection rates under similar pollen concentrations. As we cannot completely avoid pollen exposure, we suggest wide dissemination of pollen−virus coexposure information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations..."

Athanasios Damialis et al. 2021. Higher airborne pollen concentrations correlated with increased SARS-CoV-2 infection rates, as evidenced from 31 countries across the globe. PNAS, March 23, 2021 118 (12) e2019034118; https://doi.org/10.1073/pnas.2019034118 https://www.pnas.org/content/118/12/e2019034118

Significance
Coexposure to airborne pollen enhances susceptibility to respiratory viral infections, regardless of the allergy status. We hypothesized this could be also true for SARS-CoV-2 infections. To investigate this, we tested for relationships between SARS-CoV-2 infection rates and pollen concentrations, along with humidity, temperature, population density, and lockdown effects. Our unique dataset derives from 130 sites in 31 countries and across five continents. We found that pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Lockdown halved infection rates under similar pollen concentrations. As we cannot completely avoid pollen exposure, we suggest wide dissemination of pollen−virus coexposure information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations.

Abstract
Pollen exposure weakens the immunity against certain seasonal respiratory viruses by diminishing the antiviral interferon response. Here we investigate whether the same applies to the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is sensitive to antiviral interferons, if infection waves coincide with high airborne pollen concentrations. Our original hypothesis was that more airborne pollen would lead to increases in infection rates. To examine this, we performed a cross-sectional and longitudinal data analysis on SARS-CoV-2 infection, airborne pollen, and meteorological factors. Our dataset is the most comprehensive, largest possible worldwide from 130 stations, across 31 countries and five continents. To explicitly investigate the effects of social contact, we additionally considered population density of each study area, as well as lockdown effects, in all possible combinations: without any lockdown, with mixed lockdown−no lockdown regime, and under complete lockdown. We found that airborne pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Infection rates increased after higher pollen concentrations most frequently during the four previous days. Without lockdown, an increase of pollen abundance by 100 pollen/m3 resulted in a 4% average increase of infection rates. Lockdown halved infection rates under similar pollen concentrations. As there can be no preventive measures against airborne pollen exposure, we suggest wide dissemination of pollen−virus coexposure dire effect information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations.

:)

Discovery that a lysosomal* protein, TMEM106B, is required for #SARCoV2 infection through genome-wide CRISPR screening.
And it's druggable.

- Eric Topol @EricTopol | 12:17 PM · Mar 8, 2021
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Jim Baggen et al. 2021. Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2
Nature Genetics (08 March 2021) https://www.nature.com/articles/s41588-021-00805-2

Abstract
The ongoing COVID-19 pandemic has caused a global economic and health crisis. To identify host factors essential for coronavirus infection, we performed genome-wide functional genetic screens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E. These screens uncovered virus-specific as well as shared host factors, including TMEM41B and PI3K type 3. We discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. TMEM106B overexpression enhanced SARS-CoV-2 infection as well as pseudovirus infection, suggesting a role in viral entry. Furthermore, single-cell RNA-sequencing of airway cells from patients with COVID-19 demonstrated that TMEM106B expression correlates with SARS-CoV-2 infection. The present study uncovered a collection of coronavirus host factors that may be exploited to develop drugs against SARS-CoV-2 infection or future zoonotic coronavirus outbreaks.ses including SARS-CoV-2.
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Britannica: Lysosome, subcellular organelle that is found in nearly all types of eukaryotic cells and that is responsible for the digestion of macromolecules, old cell parts, and microorganisms. Each lysosome is surrounded by a membrane that maintains an acidic environment marked by the presence of hydrolytic enzymes.

Interim Public Health Recommendations for Fully Vaccinated People
CDC | Mar. 8, 2021

...Fully vaccinated people can:
Visit with other fully vaccinated people indoors without wearing masks or physical distancing
Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
Refrain from quarantine and testing following a known exposure if asymptomatic

For now, fully vaccinated people should continue to:
Take precautions in public like wearing a well-fitted mask and physical distancing
Wear masks, practice physical distancing, and adhere to other prevention measures when visiting with unvaccinated people who are at increased risk for severe COVID-19 disease or who have an unvaccinated household member who is at increased risk for severe COVID-19 disease
Wear masks, maintain physical distance, and practice other prevention measures when visiting with unvaccinated people from multiple households
Avoid medium- and large-sized in-person gatherings
Get tested if experiencing COVID-19 symptoms
Follow guidance issued by individual employers
Follow CDC and health department travel requirements and recommendations...

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.htm...

A new @NEJM report of the 3 major variants (B.1.1.7 (UK), B.1.351 (s. Africa), P.1 (Brazil), each engineered in) and
their neutralization assessed with serum from people vaccinated with 2 doses of @Pfizer /@BioNTech_Group
is quite reassuring

Fig 1 bar graph ( https://twitter.com/EricTopol/status/1369045468680884226/photo/1 )

Full text of correspondence and supplementary data, incl Fig 1 (2 p)
https://twitter.com/EricTopol/status/1369045474699702272/photo/1
https://twitter.com/EricTopol/status/1369045474699702272/photo/2

Rita E. Chen et al. (2021) Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nature Medicine 181. (March 8, 2021) https://www.nejm.org/doi/full/10.1056/NEJMc2102017

- Eric Topol @EricTopol |5:00 PM · Mar 8, 2021

Is It Ethical To Travel Internationally Before The World Is Vaccinated?
Here's what you should consider before dusting off your passport and visiting another country.
Caroline Bologna | 03/04/2021

We haven’t ruled out transmission risk.
Virus variants can be a cause for concern.
All health care infrastructure is not created equal.
There’s reason to be cautiously optimistic for the future.

...High vaccination rates and low COVID-19 rates, in both the traveler’s destination and country of origin, may make travel possible again, assuming we learn the current vaccines provide lasting immunity and considerably reduce transmission rates.

“One way to think about this is that you want to be in a fairly normal situation where your own local situation is open, with more or less normal activities albeit with masking and distancing,” (William Miller, senior associate dean for research at the Ohio State University’s College of Public Health) said. “And you want to be going to a place that is also fairly normal. And in both of those situations, you want rates low, despite the openness.”...

The answer may vary based on the destination.

If you do travel, take precautions.
...Keep your distance from others, mask up and wash your hands. Follow public health measures, and make smart decisions as the situation evolves. Make sure your travel companions, and the businesses and lodgings you plan to visit, do the same...Ultimately, it’s important to remember that your personal health isn’t the only thing that matters...

https://www.huffpost.com/entry/ethical-travel-internationally-before-world-vacci...

In Pew poll above, higher incidence of vaccine hesitancy among Latinos than among African-Americans:

Misinformation And Mistrust Among The Obstacles Latinos Face In Getting Vaccinated
Lulu Garcia-Navarro | March 7, 2021

...Oscar Londoño, executive director of WeCount!, a membership-based organization for immigrant workers in Homestead, Fla.:

...under the Trump administration, if you tapped into any services as an undocumented person, it might limit you from legalizing yourself.

...PSAs (should be) not just in Spanish, but also in many of the native Mayan indigenous languages.

...online application(s) create barriers for many low-income communities.

...additional barrier is that for housing insecure populations, what we're seeing is also that there is a requirement that many of them provide some proof that they reside in Florida...many...are living in cramped quarters, many of them are sharing a rental apartment — four, five, six, seven workers together — and the utility bill or the rental agreement might be under only one person's name.

...how many members of yours have been vaccinated? Currently, none.

...how many have been sick? Many.

https://www.npr.org/2021/03/07/974383411/misinformation-and-mistrust-among-the-o...

Stephen Goldstein (Evolutionary virology U Utah) @stgoldst | 6:25 PM · Mar 8, 2021
https://threadreaderapp.com/thread/1369066744145276928.html
12h, 17 tweets, 7 min read

There's a lot of prediction and uncertainty on the future of #SARSCoV2 in the human population.
I'll do a little thread explaining why I *think* it will end up similar to the 4 "common-cold" endemic CoVs,
but the time-scale on which this happens is up to us...

>143 margd: March 8, 2021 update of Chen et al's "NEJM report of...B.1.351 (S. Africa)...neutralization assessed with serum from people vaccinated with 2 doses of @Pfizer /@BioNTech_Group is quite reassuring."

A less optimistic take:

Pfizer, Moderna vaccines may be less effective against B1351 variant
Mary Van Beusekom | Feb 18, 2021

Both the Pfizer/BioNTech and the Moderna COVID-19 vaccines may be less effective against the B1351 variant first identified in South Africa...

In the letter on the Pfizer/BioNTech BNT162b2 coronavirus vaccine,* a team led by scientists from the University of Texas Medical Branch in Galveston made three recombinant viruses with different mutations using a SARS-CoV-2 isolate from January 2020. Using 20 serum samples collected from 15 participants in a 2020 trial of the vaccine 2 to 4 weeks after their second dose, they tested the samples' ability to neutralize the 2020 strain and all variants, including B1351 and B117.

All serum samples were able to neutralize the viruses but were about two-thirds weaker against the B1351 spike protein. However, the authors said that because the vaccines also produce other types of immune responses, such as from T cells, they may be more effective in real life than in the lab.

"Thus, it is unclear what effect a reduction in neutralization by approximately two thirds would have on BNT162b2-elicited protection from Covid-19 caused by the B.1.351 lineage of SARS-CoV-2," they wrote.

Large declines in neutralizing antibodies
The second letter, by scientists from Moderna and the National Institute of Allergy and Infectious Diseases, detailed the ability of sera from participants vaccinated in the phase 1 clinical trial of Moderna's mRNA-1273 vaccine trial to neutralize pseudovirus models.**

...they saw a 2.7-fold decrease in neutralizing antibodies against a partial panel of B1351 mutations and a 6.4-fold drop against the full set.

"Protection against the B.1.351 variant conferred by the mRNA-1273 vaccine remains to be determined," the authors said. "Our findings underscore the importance of continued viral surveillance and evaluation of vaccine efficacy against new viral variants and may help to facilitate the establishment of correlates of protection in both nonhuman primates and humans."

Clinical data have shown in previous studies that the AstraZeneca/Oxford, Novavax, and Johnson & Johnson vaccines are not as effective in preventing symptomatic infections with B1351 as against other strains. Earlier this month, South Africa put its rollout of the AstraZeneca/Oxford vaccine on hold after it was found to offer "minimal protection" against mild to moderate B1351 cases.

https://www.cidrap.umn.edu/news-perspective/2021/02/pfizer-moderna-vaccines-may-...

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* Rita E. Chen et al. 2021. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nature Medicine 181. (A preliminary version of this letter was published on February 17, 2021, and was updated March 8, 2021, at NEJM.org.) DOI: 10.1056/NEJMc2102017 https://www.nejm.org/doi/full/10.1056/NEJMc2102017

...compared with neutralization of USA-WA1/2020 (original Washington strain?), neutralization of B.1.1.7-spike and P.1-spike viruses was roughly equivalent, and neutralization of B.1.351-spike virus was robust but lower. Our data are also consistent with lower neutralization titers against the virus with the full set of B.1.351-spike mutations than against virus with either subset of mutations. Our findings also suggest that mutations that result in amino acid substitutions K417N, E484K, and N501Y in the receptor-binding site have a greater effect on neutralization than the 242–244 deletion affecting the N-terminal domain of the spike protein.

...Neutralizing activity against the B.1.351 lineage virus was robust at a geometric mean titer that was much higher than that obtained after one dose of BNT162b2 (Pfizer BioNTech vaccine), when strong efficacy was already observed in the C4591001 efficacy trial... T-cell immunity may also be involved in protection,... and BNT162b2 immunization elicits CD8+ T-cell responses that recognize multiple variants... Ultimately, conclusions about vaccine-mediated protection that are extrapolated from neutralization or T-cell data must be validated by real-world evidence collected in regions where the SARS-CoV-2 variants are circulating....

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** Kai Wu et al. 2021. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine — Preliminary Report. NEJM February 17, 2021
DOI: 10.1056/NEJMc2102179 https://www.nejm.org/doi/full/10.1056/NEJMc2102179

...we observed a decrease in titers of neutralizing antibodies against the B.1.351 (S African) variant and a subset of its mutations affecting the RBD by serum obtained from participants who had received the mRNA-1273 (Moderna) vaccine in the phase 1 trial

...in serum samples obtained from eight participants in the phase 1 trial, the geometric mean neutralizing titer against B.1.351 was 1:290...

Looking for a COVID-19 vaccine? This website may text you when a vaccine is about to go unused.
Ryan W. Miller |

A new standby list for COVID-19 vaccines is rolling out across the country to connect people with doses that would otherwise go to waste.

More than half a million people have already signed up on Dr. B ( https://hidrb.com/ ), which texts users based on their eligibility status when there are extra doses nearby in jeopardy of going unused.

https://www.usatoday.com/story/news/health/2021/03/09/how-to-get-texts-about-unu...

>132 margd: >146 margd: contd.

What the Coronavirus Variants Mean for the End of the Pandemic
The virus is mutating—but we can still beat it, one vaccination at a time.
Dhruv Khullar | March 7, 2021

...Like all viruses, SARS-CoV-2 will continue to evolve. But (Jason McLellan, a structural biologist at the University of Texas at Austin ) believes that it has a limited number of moves available. “There’s just not a lot of space for the spike to continue to change in ways that allow it to evade antibodies but still bind to its receptor,” he said. “Substitutions that allow the virus to resist antibodies will probably also decrease its affinity for ACE-2”—the receptor that the virus uses to enter cells. Recently, researchers have mapped the universe of useful mutations available to the spike’s receptor-binding area. They’ve found that most of the changes that would weaken the binding ability of our antibodies occur at just a few sites; the E484K substitution seems to be the most important. “The fact that different variants have independently hit on the same mutations suggests we’re already seeing the limits of where the virus can go,” McLellan told me. “It has a finite number of options.”

Over time, SARS-CoV-2 is likely to become less lethal, not more. When people are exposed to a virus, they often develop “cross-reactive” immunity that protects them against future infection, not just for that virus, but also for related strains; with time, the virus also exhausts the mutational possibilities that might allow it to infect cells while eluding the immune system’s memory. “This is what we think happened to viruses that cause the common cold,” McLellan said. “It probably caused a major illness in the past. Then it evolved to a place where it’s less deadly. But, of course, it’s still with us.” It’s possible that a coronavirus that now causes the common cold, OC43, was responsible for the “Russian flu” of 1889, which killed a million people. But OC43, like other coronaviruses, became less dangerous with time. Today, most of us are exposed to OC43 and other endemic coronaviruses as children, and we experience only mild symptoms. For SARS-CoV-2, such a future could be years or decades away...

...In a way, the beginning of the pandemic was simple: the virus was spreading, and we had to stop it. Its ending will be more complicated. While the arrival of the virus changed life swiftly and decisively, our return to normalcy won’t mirror our departure from it. There probably won’t be a day, week, or month when the U.S. rises out of the pandemic, with a “Mission Accomplished” banner unfurled overhead. Instead, as more of the population gains immunity, either through infection or inoculation, daily life will become less risky. We’ll feel more comfortable running errands and seeing friends. More of us will trek to the office, board planes, eat in restaurants. With time, concerts, weddings, and spin classes will return, too. The variants may postpone or complicate this reality, but they won’t foreclose it. A likely future is one in which most Americans are protected by the end of the summer. From there, we will line up for coronavirus booster shots the way we do for flu vaccines. The virus will linger and it will evolve. New variants, constrained by the virus’s molecular limitations, will arise, in a game of evolutionary cat and mouse. But, step by step, our old rhythms will return. We’ll end up finding a new equilibrium, one more favorable to humanity than to the virus—a slight variation on the way we used to live.

https://www.newyorker.com/science/medical-dispatch/what-the-coronavirus-variants...

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ETA: cartoon :D
https://twitter.com/EricTopol/status/1369658228234022915/photo/1

Did you feel that your arm is on "fire" after SARS-CoV-2 mRNA vaccine? We looked at the lymph nodes draining the arm after mRNA vaccination in humans and those nodes DID have raging fires .. good kind of fires. We call them germinal centers.
- Ali Ellebedy @TheBcellArtist | 7:46 PM · Mar 9, 2021

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Ali Ellebedy...Florian Krammer... et al. 2021. SARS-CoV-2 mRNA vaccines induce a robust germinal centre reaction in humans. Research Square. March 2, 2021. DOI: 10.21203/rs.3.rs-310773/v1 https://www.researchsquare.com/article/rs-310773/v1

This preprint is under consideration at a Nature Portfolio Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal.

Abstract
... Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a robust and persistent GC B cell response that engages pre-existing as well as new B cell clones, which enables generation of high-affinity, broad, and durable humoral immunity.

Ashish K. Jha, MD, MPH @ashishkjha | 11:27 PM · Mar 9, 2021

Worried about B.1.1.7 (variant originally found in UK) causing a major spike in the US?
Florida is probably our best early signal
Likely has highest proportion of B.1.1.7 infections in nation
So here's graph so far in 2021. Steady, slow decline
No bump yet
Fingers crossed

Image ( https://twitter.com/ashishkjha/status/1369505146485489665/photo/1 )

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Interesting discussion ensued in response to Dr Jha tweet:
https://twitter.com/ashishkjha/status/1369505146485489665

Long COVID: "...13.3% participants reported symptoms lasting 28 or more days, 4.5% for 8 weeks or more and 2.3% for 12 weeks or more. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53)..."

Carole H. Sudre et al. Attributes and predictors of long COVID. Nature Medicine (10 March 2021) https://www.nature.com/articles/s41591-021-01292-y

Abstract
Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called ‘long COVID’, are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76–4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.