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

B117 (variant of concern 202012/1) compared to previously circulating variants, UK:
"In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases."
Risk grew after 12 days.
(Happily, B117 is susceptible to vaccines, masks, social distancing, etc. )

Robert Challen et al. 2021. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study (Research).
BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n579 (Published 10 March 2021) Cite this as: BMJ 2021;372:n579 https://www.bmj.com/content/372/bmj.n579

Abstract
...
Design Matched cohort study.

Main outcome measure Death within 28 days of the first positive SARS-CoV-2 test result.

Results The mortality hazard ratio associated with infection with VOC-202012/1 compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community. In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases.

Conclusions The probability that the risk of mortality is increased by infection with VOC-202012/01 is high. If this finding is generalisable to other populations, infection with VOC-202012/1 has the potential to cause substantial additional mortality compared with previously circulating variants. Healthcare capacity planning and national and international control policies are all impacted by this finding, with increased mortality lending weight to the argument that further coordinated and stringent measures are justified to reduce deaths from SARS-CoV-2.

Above my pay grade, but good to see latter (deadly) stage of COVID-19 better understood: "Comparing (hospitalized and mild COVID) profiles to archived samples from patients with fatal influenza, IL-6* was equally elevated in both conditions whereas GM-CSF** was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

* Interleukin 6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. (Wikipedia)

** Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim. (Wikipedia)

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Ryan S Thwaites et al. 2021. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Science Immunology 10 Mar 2021: Vol. 6, Issue 57, eabg9873. DOI: 10.1126/sciimmunol.abg9873

Abstract
While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

Why comparing Covid-19 vaccine efficacy numbers can be misleading
The best Covid-19 vaccine for you is most likely still the first one you can get.
Umair Irfan | Mar 5, 2021

https://www.vox.com/22311625/covid-19-vaccine-efficacy-johnson-moderna-pfizer

Individuals with pre-existing immunity to SARS-CoV-2 respond strongly to the first dose of mRNA vaccine,
equal or better than naive individuals to the second dose...
- Florian Krammer @florian_krammer | 7:23 PM · Mar 10, 2021

Florian Krammer et al. 2021. Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine (Correspondence). The New England Journal of Medicine (March 10, 2021) DOI: 10.1056/NEJMc2101667 https://www.nejm.org/doi/full/10.1056/NEJMc2101667

...Most common were localized injection-site symptoms (pain, swelling, and erythema (redness of the skin)), which occurred with equal frequency independently of the serostatus at the time of vaccination and resolved spontaneously within days after vaccination. Vaccine recipients with preexisting immunity had systemic side effects at higher frequencies than those without preexisting immunity (fatigue, headache, chills, muscle pain, fever, and joint pain, in order of decreasing frequency) (Figure 1B).

...We found that a single dose of mRNA vaccine elicited rapid immune responses in seropositive participants, with postvaccination antibody titers that were similar to or exceeded titers found in seronegative participants who received two vaccinations. Whether a single dose of mRNA vaccine provides effective protection in seropositive persons requires investigation...

Eric Topol @EricTopol | 12:12 PM · Mar 11, 2021:

New data from 5 billion medical records highlights the risk of dying from covid largely driven by age, but risk of hospitalization by comorbidities (as seen well in this graph among young) TheEconomist

https://economist.com/graphic-detail/2021/03/13/our-covid-19-model-estimates-odd...
Image ( https://twitter.com/EricTopol/status/1370060163550355456/photo/1 )

Eric Topol (physician scientist) @EricTopol | 1:54 PM · Mar 11, 2021:
A new @Mayoclinic study adds to many recent reports on the ~80% suppression of the carrier state, asymptomatic transmission, with 1 and 2 doses of mRNA vaccines

Image-graph cumulative positives v no. days after 1st and 2nd doses
( https://twitter.com/EricTopol/status/1370085788352868352/photo/1 )

Aaron J Tande et al. 2021. Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening. Clinical Infectious Diseases, ciab229 (Accepted manuscript, 10 March 2021), https://doi.org/10.1093/cid/ciab229 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab229/6167855

Abstract
Background
Methods

Results
Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on (mRNA) vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44...). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those more than 10 days after 1st dose (RR=0.21...) and more than 0 days after 2nd dose (RR=0.20...) in the adjusted analysis.

Conclusions
COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients....

Covid: Does Tanzania have a hidden epidemic? (BBC)

Despite growing evidence to the contrary, Tanzania's government continues to downplay the impact of coronavirus on the country. There is also speculation that President Magufuli is himself suffering from Covid and receiving hospital treatment, although that has not been confirmed. There are no publicly available records for recent deaths in Tanzania, and no information has been released on the impact of coronavirus since May last year, when 500 cases and 20 deaths were reported up to that point. The authorities have insisted there is little to worry about, and have taken tough action against those they accuse of spreading "false information"...

European Countries Suspend Use of AstraZeneca Shots Over Worries About Blood Clots
Rebecca Robbins and Thomas Erdbrink | March 11, 2021

Health authorities in three European countries on Thursday suspended use of AstraZeneca’s vaccine because of concerns that it might increase the risk of blood clots, but emphasized that they were taking action as a precaution and that there is no evidence of any causal link.

Denmark acted after a 60-year-old woman who received a shot died after developing a blood clot. Several other European countries had recently stopped using doses from the same batch of the vaccine after some reports of severe blood clots, and European drug regulators are investigating.

In the flurry of suspensions on Thursday, Norway and Iceland followed Denmark’s lead. Italy and Romania also paused shots, but only from a different batch of the vaccine than the one that had raised concerns elsewhere.

Public health experts expect medical conditions to turn up by chance in some people after they get any vaccine, just by chance. In the vast majority of cases such illnesses have nothing to do with the shots. Most other countries where the vaccine has been given to many millions of people have not reported similar red flags...

https://www.nytimes.com/2021/03/11/business/astrazeneca-vaccine-denmark-blood-cl...

The U.S. Is Sitting on Tens of Millions of Vaccine Doses the World Needs
Noah Weiland and Rebecca Robbins | March 11, 2021

Those tens of millions of doses from AstraZeneca are waiting for trial results, while countries that authorized the vaccine beg to have them.

...“If we have a surplus, we’re going to share it with the rest of the world,” Mr. Biden told reporters on Wednesday, speaking generally about the U.S. vaccine supply. “We’re going to start off making sure Americans are taken care of first.”...

https://www.nytimes.com/2021/03/11/us/politics/coronavirus-astrazeneca-united-st...
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Ashish K. Jha, MD, MPH (Dean Howard SPH) @ashishkjha | 8:23 AM · Mar 12, 2021
Thousands of people dying from COVID every day around the world
Large outbreaks elsewhere breeding ground for new variants
And we are sitting on tens of millions of AZ vaccines that at this point, I'm pretty sure we'll never use
Time to give them away

Novavax Confirms High Levels of Efficacy Against Original and Variant COVID-19 Strains in United Kingdom and South Africa Trials
Novavax News Release | Mar 11, 2021

100% protection against severe disease
Final analysis in U.K. trial confirms 96% efficacy against original strain of COVID-19
Efficacy against variants confirmed in U.K. and South Africa

"...efficacy of 55.4% among the HIV- negative trial participants in (South Africa) where the vast majority of strains are B1.351 escape variants...100% protection against severe disease, including all hospitalization and death..."

In the UK "efficacy was 96.4% ... against the original virus strain and 86.3% ... against the B.1.1.7/501Y.V1 variant"...

...NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax’ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is adjuvanted with Novavax’ patented saponin-based Matrix-M™ to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19. ...

NVX-CoV2373 is stored and stable at 2°- 8°C, allowing the use of existing vaccine supply chain channels for its distribution. It is packaged in a ready-to-use liquid formulation in 10-dose vials.

https://ir.novavax.com/news-releases/news-release-details/novavax-confirms-high-...

Eric Topol @EricTopol | 11:39 AM · Mar 12, 2021
The vaccines and the variants: new @CellCellPress today, assessment of mRNA vaccines vs multiple strains and mutations
B.1.1.7 (UK) not an issue;
2 doses greater than 1;
B.1.351 (S Africa) the major concern but many non-RBD nAbs can kick in...

Image ( https://twitter.com/EricTopol/status/1370414275328573441/photo/1 )
Image ( https://twitter.com/EricTopol/status/1370414275328573441/photo/2 )
Ragon Institute

Wilfredo F. Garcia-Beltran et al. 2021. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell (March 12, 2021) DOI:https://doi.org/10.1016/j.cell.2021.03.013 https://www.cell.com/cell/fulltext/S0092-8674(21)00298-1

Highlights
● Numerous variants of SARS-CoV-2 harboring mutations in spike have arisen globally
● mRNA vaccines elicit potent neutralizing activity against homologous pseudovirus
● Cross-neutralization of strains with receptor binding domain (RBD) mutations is poor
● Both RBD and non-RBD mutations mediate escape from vaccine-induced humoral immunity

Summary
Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

In Peru, the sun helps vaccines keep their cool (1:44 -- English subtitles)
Unicef Perú•Mar 8, 2021

Solar-powered freezers, procured through UNICEF, will help COVID-19 and other routine vaccines reach Peru’s remote communities.

https://www.youtube.com/watch?v=TIn-xxN6o-s

Testimony (13 p) from witness
Dr. Linsey Marr, Ph.D., Professor of Civil and Environmental Engineering
Virginia Polytechnic Institute and State University, Blacksburg , VA

Protection Against Transmission of COVID-19
(1) how COVID-19 is transmitted mainly by breathing in aerosol particles carrying the virus,
(2) how best to protect workers and the public through the use of appropriate face coverings and other controls, and
(3) what updates are needed to CDC’s guidance.
I will conclude by stating what needs to be done to protect workers and the public from becoming infected.
https://edlabor.house.gov/imo/media/doc/MarrLinseyTestimony03112021.pdf

at

Workforce Protections Subcommittee Hearing
Clearing the Air: Science-Based Strategies to Protect Workers from COVID-19 Infections (2:18:00)
Thursday, March 11, 2021
https://edlabor.house.gov/hearings/clearing-the-air-science-based-strategies-to-...

U.S., India, Japan and Australia counter China with billion-dose vaccine pact
David Brunnstrom, Michael Martina, Jeff Mason | March 12, 2021

WASHINGTON (Reuters) - The United States and three of its closest Indo-Pacific partners (Australia, India and Japan) committed to supplying up to a billion coronavirus vaccine doses across Asia by the end of 2022 at a summit on Friday carefully choreographed to counter China’s growing influence.

President Joe Biden and the leaders of Australia, India and Japan - countries together known as the Quad - pledged at their first summit to work to ensure a free and open Indo-Pacific and to cooperate on maritime, cyber and economic security, issues vital to the four democracies in the face of challenges from Beijing.

In a joint statement, Biden, Japanese Prime Minister Yoshihide Suga, Indian Prime Minister Narendra Modi, and Australian Prime Minister Scott Morrison, pledged to work closely on COVID-19 vaccine distribution, climate and security.

...The leaders agreed to set up an experts’ group to help distribute vaccines, as well as working groups on climate change, technology standards, and joint development of emerging technologies. An in-person summit would be held later this year, they said.

...India’s Foreign Secretary Harsh Vardhan Shringla said the summit had agreed U.S. vaccines would be manufactured in India, something New Delhi has called for to counter Beijing’s widening vaccine diplomacy.

A Quad fact sheet said the United States, through its International Development Finance Corp, would work to finance Indian drugmaker Biological E Ltd to produce at least 1 billion COVID-19 vaccine doses by the end of 2022.

It also said Japan was in discussions to provide concessional yen loans for India to expand manufacturing of COVID-19 vaccines for export.

https://www.reuters.com/article/us-usa-asia/u-s-india-japan-and-australia-agree-...

_________________________________________________

ETA...vaccine wars...

China asks visa applicants to get inoculated with Chinese-made vaccines.
Keith Bradsher | March 13, 2021

China raised the stakes in the international vaccine competition on Saturday, saying that foreigners wishing to enter the Chinese mainland from Hong Kong will face fewer paperwork requirements if they are inoculated with Chinese-made coronavirus vaccines.

The policy announcement, which covers foreigners applying for visas in the Chinese territory, comes a day after the United States, India, Japan and Australia announced plans to provide vaccines more widely to other countries. ...

https://www.nytimes.com/2021/03/12/world/china-vaccines-hong-kong.html

Eric Topol @EricTopol | 9:06 PM · Mar 14, 2021:
6 (changed to) 3 feet "rule" for schools?
A new study getting considerable interest CNN, @nytimes
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab230/6167856?sea... *
and
https://wsj.com/articles/how-to-make-spring-the-last-lost-semester-11615755948?m... **

Image--graph of staff and student cases at 6 and 3 ft ( https://twitter.com/EricTopol/status/1371266606727237635/photo/1 )
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* Polly van den Berg et al. 2021. Effectiveness of three versus six feet of physical distancing for controlling spread of COVID-19 among primary and secondary students and staff: A retrospective, state-wide cohort study. Clinical Infectious Diseases ( Accepted manuscript, 10 March 2021 ), ciab230, https://doi.org/10.1093/cid/ciab230 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab230/6167856

Abstract
Background
National and international guidelines differ about the optimal physical distancing between students for prevention of SARS-CoV-2 transmission; studies directly comparing the impact of ...3 versus...6 feet of physical distancing policies in school settings are lacking. Thus, our objective was to compare incident cases of SARS-CoV-2 in students and staff in Massachusetts public schools among districts with different physical distancing requirements. State guidance mandates masking for all school staff and for students in grades 2 and higher; the majority of districts required universal masking.

Methods
Community incidence rates of SARS-CoV-2, SARS-CoV-2 cases among students in grades K-12 and staff participating in-person learning, and district infection control plans were linked. Incidence rate ratios (IRR) for students and staff members in districts with ...3 versus ...6 feet of physical distancing were estimated using log-binomial regression; models adjusted for community incidence are also reported.

Results
Among 251 eligible school districts, 537,336 students and 99,390 staff attended in-person instruction during the 16-week study period, representing 6,400,175 student learning weeks and 1,342,574 staff learning weeks. Student case rates were similar in the 242 districts with ...feet versus ...6 feet of physical distancing between students (IRR, 0.891...); results were similar after adjusting for community incidence (adjusted IRR, 0.904...). Cases among school staff in districts with ...3 feet versus feet of physical distancing were also similar (IRR, 1.015...).

Conclusions
Lower physical distancing policies can be adopted in school settings with masking mandates without negatively impacting student or staff safety.

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** How to Make Spring the Last Lost Semester ( PAYWALL )
With Covid precautions and eventual vaccines for children, classrooms can reopen in time for the fall.
Scott Gottlieb and Caitlin Rivers | March 14, 2021
https://wsj.com/articles/how-to-make-spring-the-last-lost-semester-11615755948?m...

Exclusive: Regular booster vaccines are the future in battle with COVID-19 virus, top genome expert says
Guy Faulconbridge | March 15, 20214:36 AMUpdated 44 minutes ago

CAMBRIDGE, England (Reuters) - Regular booster vaccines against the novel coronavirus will be needed because of mutations that make it more transmissible and better able to evade human immunity, the head of Britain’s effort to sequence the virus’s genomes told Reuters.

The novel coronavirus, which has killed 2.65 million people globally since it emerged in China in late 2019, mutates around once every two weeks, slower than influenza or HIV, but enough to require tweaks to vaccines.

Sharon Peacock, who heads COVID-19 Genomics UK (COG-UK) which has sequenced nearly half of all the novel coronavirus genomes so far mapped globally, said international cooperation was needed in the “cat and mouse” battle with the virus....

https://www.reuters.com/article/us-health-coronavirus-britain-peacock-ex/exclusi...

#115 in thread 16, contd. :(

"Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness."

Davies, N.G., Jarvis, C.I., CMMID COVID-19 Working Group. et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature (2021). https://doi.org/10.1038/s41586-021-03426-1 https://www.nature.com/articles/s41586-021-03426-1

Unedited manuscript that has been accepted for publication

Abstract
SARS-CoV-2 lineage B.1.1.7, a variant first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39–72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8–1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42–82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness.

Kai Kupferschmidt (Science Magazine)
@kakape 12:50 PM · Mar 15, 2021
https://threadreaderapp.com/thread/1371504153277644800.html
“More countries have suspended the use of AstraZeneca vaccines as a precautionary measure, after reports of blood clots in people who had received the vaccine from two batches produced in Europe”, says @DrTedros (Director General WHO) at WHO presser on #covid19.

"This does not necessarily mean these events are linked to vaccination”, says (Tedros). "WHO’s Advisory Committee on Vaccine Safety has been reviewing the available data, is in close contact with the (EU Medicines Agency) and will meet tomorrow."

"What we can say so far: It doesn't look like there are more cases than would be expected for the period in the general population”, says
@mariangelasimao (Assistant DG WHO). From data so far, "there is not an increasing number of cases of thromboembolic events."
“While we need to continue to be very closely monitoring this, we do not want people to panic”, says @doctorsoumya (Chief Scientist). “We would, for the time being recommend that countries continue vaccinating with AstraZeneca.”

Also pointed out by @mariangelasimao that safety concerns that have been raised are for AZ vaccine batches produced in Europe while AZ vaccine for COVAX is being produced in South Korea and in India...

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ETA

Eric Feigl-Ding @DrEricDing | 6:33 AM · Mar 16, 2021:
The AstraZeneca vaccine—okay, I think it’s too speculative to say if any real clotting yet.
The temporary suspensions might scare some—
but the fact that it was suspended out of **over abundance of caution** should be a good sign.
Good video @BBCRosAtkins

6:46 ( https://twitter.com/DrEricDing/status/1371771708336713731 )
From Ros Atkins (BBC Outside Source)

Hope long COVID patients' anecdotal reports of relief after vaccination are not due to placebo effect. Study (preprint below) would have been stronger if controls had received shot of some kind, and neither group knew which they had received(?)

David T Arnold et al. 2021. Are vaccines safe in patients with Long COVID? A prospective observational study. MedRxiv ()
doi: https://doi.org/10.1101/2021.03.11.21253225 https://www.medrxiv.org/content/10.1101/2021.03.11.21253225v2

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

Abstract
"those who had receive(d) a (Pfizer-BioNTech or Oxford-AstraZeneca) vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated)"

Eric Topol @EricTopol | 9:38 AM · Mar 16, 2021
Good graph showing the association of vaccination and case spread by country, per capita
The notable exceptions are Chile (high vaccination rate) and Spain (low)

Image ( https://twitter.com/EricTopol/status/1371818066183483392/photo/1 )

Europe’s Vaccine Mess
New coronavirus cases are declining in countries with high vaccination rates. Then there is Europe.
David Leonhardt | March 16, 2021, 6:21 a.m. ET
https://nytimes.com/2021/03/16/briefing/blood-clots-oscar-nominees-opioid-purdue...

France and Finland discovered variants that escape detection by standard PCR tests...

Eric Feigl-Ding
18 tweets
https://twitter.com/DrEricDing/status/1371868437803372551
https://threadreaderapp.com/thread/1371855414611034122.html

Variant “bypasses” PCR tests—French govt is warning of a new #SARSCoV2 variant that escapes detection by standard PCR tests. Because is it harder to detect, WHO has placed it in category of “variant under investigation” due to its bypassing PCR tests

2) Good thing is that so far, the “initial analyses of this new variant doesn’t suggest either increased severity or increased transmissibility”.

3) However, the French authorities are not fooling around — they have released an URGENT bulletin warning about this new variant that was discovered in Brittany (of France).
...
13) Is France the only country to notice such a new variant that evades PCR tests? No, Finland 🇫🇮 also just discovered a new variant that escapes classic PCR lab tests too
...
15) THINK OF IT THIS WAY—its remarkable that the virus may have actually somehow selectively evolved a mutation that allows it to surreptitiously transmit farther by evolving a mutation that goes less detected! Just when we think we figured it out, it mutates a new hat trick.

16) But wanna know what works against such a variant? It’s easy...
Masks. Ventilation. Vaccination.
They still work—even without testing. This is why mitigation measures have to stay in place for a while even after vaccination...

__________________________________________________
ETA

French health ministry warns of new coronavirus variant that may be able to evade PCR tests
THE WEEK | March 16, 2021

...The variant was reportedly first detected in a cluster of eight cases at a hospital in Lannion. Despite the patients displaying conventional COVID-19 symptoms, PCR tests were reportedly not able to pick up the presence of the virus. Reports The Local, Brittany has maintained one of France's lower infection rates, but the recent discovery has raised concerns that some cases were missed. Of course, it's certainly possible the errors could have been related to the tests themselves, rather than any genetic modifications to the virus...

https://theweek.com/speedreads/972363/french-health-ministry-warns-new-coronavir...

__________________________________________________
ETA

New French coronavirus variant appears to bypass standard tests
The strain is in the WHO’s ‘variant under investigation’ category.
Elisa Braun | March 16, 2021
https://www.politico.eu/article/new-french-coronavirus-variant-might-bypass-pcr-...

#107 in thread 19 "Republicans are least likely to want the coronavirus vaccine"

On the vaccine, Trump tells his hesitant supporters: ‘I would recommend it.’
Bryan Pietsch | March 16, 2021

...Mr. Trump and his wife, Melania, were vaccinated in secret in January. Vaccine proponents have been calling on him to speak more forcefully in favor of the shots to his legions of supporters, many of whom remain reluctant, polls show.

Speaking to Maria Bartiromo on “Fox News Primetime” on Tuesday evening, Mr. Trump said, “I would recommend it, and I would recommend it to a lot of people that don’t want to get it, and a lot of those people voted for me frankly.”

He added: “It is a safe vaccine, and it is something that works.”...

...Still, Mr. Trump — whose tenure during the pandemic was often marked by railing against recommendations from medical experts — said on Tuesday that “we have our freedoms and we have to live by that, and I agree with that also.”...

https://www.nytimes.com/2021/03/16/world/covid-vaccine-trump.html
______________________________________________
ETA

Faith leaders get COVID-19 shot to curb vaccine reluctance
MANUEL BALCE CENETA | 03/17/2021

WASHINGTON (AP) — More than two dozen clergy members from the capital region rolled up their sleeves inside the Washington National Cathedral and got vaccinated against the coronavirus Tuesday in a camera-friendly event designed to encourage others to get their own COVID-19 shots.

The interfaith “vaccine confidence” event targeted in particular Black, Latino and other communities of color, with the aim of overcoming reluctance among populations disproportionately hit by a pandemic that has killed more than a half-million people in the country...

https://apnews.com/article/pandemics-race-and-ethnicity-health-disparities-coron...

"vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection"

Israeli study: Babies born to vaccinated moms have COVID-fighting antibodies
Nathan Jeffay | 16 March 2021

...A team at Hadassah Medical Center in Jerusalem checked blood from the umbilical cords of 40 newborns, which is the same as the baby’s blood, and found that all had a strong supply of antibodies — just like their mothers who had been vaccinated with the Pfizer-BioNTech shots.

Believed to be the largest study of its kind, the researchers believe that the find vindicates health officials’ call to pregnant women to get vaccinated against the coronavirus. And with the world constantly looking to Israel for new data on the impact of vaccines, the finding is likely to have strong international resonance.

“This is an important finding that is reassuring, suggesting that vaccinated mothers pass COVID-19 protection to their babies before they are born,” Prof. Dana Wolf, head of Hadassah’s virology department...“It underscores the importance of vaccinating pregnant women, and the benefits of doing so.”

...Wolf noted that initially, health authorities did not recommend pregnant women receive the vaccine, but recently the Center for Disease Control and Prevention, the World Health Organization, Israel’s Ministry of Health and others supported immunizing pregnant women. She said her study offers further vindication of this decision.

Partial results from the research — covering half of the babies examined — have been posted online in an early version of the study, that is not yet peer-reviewed.* The findings come on the heels of another Israeli study that suggests that vaccinated mothers pass antibodies to their newborns through breast milk.

“In our study, we found immunoglobulin G antibodies that are active against the spike protein of SARS-CoV-2, which basically block the entry of the virus to cells. This follows research which suggests that great milk has another type of antibodies, Immunoglobulin A,” said Wolf.

She said that the research has not established with certainty that the antibodies deliver protection against infection, but she strongly believes they will. There is, she noted, no information on how long the babies will retain their antibodies, or any protection they may provide.

Wolf conducted her research with colleagues from Hadassah’s obstetrics and gynecology department, including Amihai Rottenstreich and Shay Potrat...

https://www.timesofisrael.com/israeli-study-babies-born-to-vaccinated-moms-have-...

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* Amihai Rottenstreich et al. 2021. Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination. MedRxiv (March 12, 2021) doi: https://doi.org/10.1101/2021.03.11.21253352 https://www.medrxiv.org/content/10.1101/2021.03.11.21253352v1

This article is a preprint and has not been peer-reviewed.

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy and early infancy can result in severe disease. Evaluating the serologic response after maternal vaccination during pregnancy and subsequent transplacental antibody transfer has important implications for maternal care and vaccination strategies.

Objective
To assess maternal and neonatal SARS-CoV-2 antibody levels after antenatal mRNA vaccination.

Design, Setting, and Participants
This study took place at Hadassah Medical Center in Jerusalem, Israel in February 2021. Maternal and cord blood sera were collected for antibody measurement from mother/newborn dyads following antenatal vaccination.

Exposure
SARS-CoV-2 BNT162b2 mRNA vaccination.

Main outcome and measures
Spike protein (S) and receptor binding domain (RBD) - specific, IgG levels were evaluated in maternal and cord blood sera.

Results
The study cohort consisted of 20 parturients, with a median maternal age of 32 years and a median gestational age of 393/7 weeks at the time of delivery. The median time lapsed from the first and second doses of vaccine administration until delivery was 33 ... and 11... days, respectively. Of the 20 dyads, all women and infants were positive for anti S- and anti-RBD-specific IgG. Anti-S and anti-RBD-specific IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood (ρs= 0.72...). Anti-S and anti-RBD-specific IgG titers in cord blood were directly correlated with time lapsed since the administration of the first vaccine dose (ρs= 0.71... and ρs= 0.63..., respectively).

Conclusion and Relevance
In this study, SARS-CoV-2 mRNA vaccine administered during pregnancy induced adequate maternal serologic response with subsequent efficient transplacental transfer. Our findings highlight that vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection.

Interesting read:

The AstraZeneca COVID-19 Vaccine And Risk of Blood Clots: What You Need to Know
GIDEON MEYEROWITZ-KATZ | 17 MARCH 2021
https://www.sciencealert.com/a-scientist-explains-why-you-don-t-need-to-panic-ab...

COVID-19: mRNA vaccines reduce symptom-free cases by 80%
James Kingsland | March 16, 2021

People with SARS-CoV-2, which is the virus that causes COVID-19, who show no symptoms may account for more than half of all transmission cases of the disease.

A new study helps alleviate concerns that people who have been vaccinated may still be vulnerable to symptom-free, or “asymptomatic,” COVID-19 and will, therefore, spread the virus to others.

The study suggests that people who have had two doses of a messenger RNA (mRNA) vaccine are 80% less likely to develop asymptomatic COVID-19 than people who have not been vaccinated....

https://www.medicalnewstoday.com/articles/covid-19-mrna-vaccines-reduce-symptom-...

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Aaron J Tande et al. 2021. Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening. Clinical Infectious Diseases, ciab229, (10 March 2021) https://doi.org/10.1093/cid/ciab229 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab229/6167855

Accepted manuscript.

Abstract
Background
Several vaccines are now clinically available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. The impact of vaccines on asymptomatic SARS-CoV-2 infection is largely unknown.

Methods
We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39,156) within a large United States healthcare system who underwent 48,333 pre-procedural SARS-CoV-2 molecular screening tests between December 17, 2020 and February 8, 2021. The primary exposure of interest was vaccination with at least one dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received at least one dose of vaccine, as compared to persons who had not received vaccine during the same time period. Relative risk was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs. non-local), healthcare system regions, and repeated screenings among patients using mixed effects log-binomial regression.

Results
Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44 ...). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those more than 10 days after 1 st dose (RR=0.21...) and more than 0 days after 2nd dose (RR=0.20...) in the adjusted analysis.

Conclusions
COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

Any virus is one micron. Human eyes are 52,000 microns across, multiplied by the height. Humans have eustachian tubes to their lungs. Little masks do not stop sheetrock dust from the mouth, which is often a thousand times bigger than a virus. No one is using a scanning electron microscope in autopsy to verify this one particular virus is present in the dead. Further, the mere presence is not automatically an indicator that the virus was the proximate cause of death. It is upside down. One does not diagnose a death by submitting that any of ten symptoms indicates a death. That is like saying milk is a gateway drug. It is not proper diagnostic epidemiology. Were the National Guardsmen at the Capitol event in January wearing TeleTubby suits? No?

Masks don't have to block all virus particles to slow down the spread of covid-19 since it takes a certain minimum number of virii for a person to become infected. It's also true that many of the virii are embedded in droplets that are effectively caught by cloth masks.

Do you really believe that nearly the entire medical establishment has made a simple mistake?

>27 jjwilson61: reminds me of a cartoon I saw recently of a guy at his computer and the caption: “Honey come look! I’ve discovered some information all the world’s scientists and doctors missed.”

Monoclonal antibodies could be Plan B for COVID-19 (after vaccines), but, given speed of development, the approach could be Plan A in future pandemics.

COVID antibody treatments show promise for preventing severe disease
But uptake by patients and physicians has been low in the United States, where some therapies have been authorized for months
Heidi Ledford (Nature News) | 12 March 2021

Two clinical trials suggest that specific antibody treatments can prevent deaths and hospitalizations among people with mild or moderate COVID-19 — particularly those who are at high risk of developing severe disease.

One study found that an antibody against the coronavirus developed by Vir Biotechnology in San Francisco, California, and GSK, headquartered in London, reduced the chances of hospitalization or death among participants by 85%. In another trial, a cocktail of two antibodies — bamlanivimab and etesevimab, both made by Eli Lilly of Indianapolis, Indiana — cut the risk of hospitalization and death by 87%.

The study results, both announced on 10 March, come from randomized, placebo-controlled, double-blind clinical trials, but have not yet been published.

...Vir and GSK’s antibody, called VIR-7831, was first isolated in 2003 from someone recovering from severe acute respiratory syndrome (SARS), which is caused by a similar coronavirus. The antibody was later found to bind to the SARS-CoV-2 ‘spike’ protein, too...in laboratory studies1, VIR-7831 bound to SARS-CoV-2 variants — including the fast-spreading 501Y.V2 variant (also called B.1.351) first identified in South Africa. They attributed the resilience of the antibody to its target: a particular region of the spike protein that does not tend to accumulate mutations.

...relatively little uptake by US physicians and their patients...results have been press released and submitted to the US Food and Drug Administration, companies have yet to publish data from key clinical trials in peer-reviewed journals...expensive and must be administered by infusion in a specialized facility, such as a hospital or outpatient-treatment centre...mixed messaging (i.e.,) expected to work best early in disease (but early tests later in disease process showed no benefit)

...studies in mild infections...too small to allow researchers to draw definitive conclusions...Only a small fraction of people with mild COVID-19 will progress to severe disease

...monoclonal antibodies could provide an important bridge between vaccines and the treatments that have been found for people who are hospitalized

The speed with which these monoclonal antibodies were developed holds a lesson for future pandemics...

doi: https://doi.org/10.1038/d41586-021-00650-7
https://www.nature.com/articles/d41586-021-00650-7

Older people especially vulnerable to coronavirus reinfection without vaccine, study says
Erin Cunningham | March 18, 2021

...The study by Danish researchers has highlighted the importance of vaccinating elderly populations, as well as previously infected individuals, as the pandemic wears on, according to the authors. Researchers found that natural infection reduced the chances of getting the virus again by about 80 percent, but offered just 47 percent protection against repeat infection among those over 65.

Two British immunologists commenting on the results also in the Lancet called the protective immunity from natural infection “poor” relative to the immune response elicited by current coronavirus vaccines. “The hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” they said in an article linked to the study...

https://www.washingtonpost.com/nation/2021/03/18/
deep down in "coronavirus-covid-live-updates-us/"

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Christian Holm Hansen et al. 2021. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. The Lancet (Articles|Online First.Published:March 17, 2021) DOI:https://doi.org/10.1016/S0140-6736(21)00575-4 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00575-4/fullt...

Summary
Background...

Methods
In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR.

Findings
During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% ...) tested positive again during the second surge compared with 16 819 (3·27% ...) of 514 271 who tested negative during the first surge (adjusted RR 0·195 ...). Protection against repeat infection was 80·5% (95% ...). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 ..., estimated protection 78·8% ...). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% .... We found no difference in estimated protection against repeat infection by sex (male 78·4% ... vs female 79·1% ...) or evidence of waning protection over time (3–6 months of follow-up 79·3% ... vs 7 months or more of follow-up 77·7%...).

Interpretation
Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

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Rosemary J Boyton and Daniel M Altmann. 2021. Risk of SARS-CoV-2 reinfection after natural infection. The Lancet (Comment|Online First. March 17, 2021 DOI:https://doi.org/10.1016/S0140-6736(21)00662-0 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00662-0/fullt...

Since the start of the COVID-19 pandemic, the question of potential reinfection has been ever present. Although there has been much debate about potential reliance on herd immunity through natural infection, human coronaviruses are well adapted to subvert immunity...and reinfection occurs for seasonal coronaviruses (229E, OC43, NL63, and HKU1) that cause the common cold due to ephemeral immunity that is poorly protective between infections...

Furthermore, detailed mapping of immune parameters in cohorts such as health-care workers emphasises the heterogeneity of immune responsiveness to SARS-CoV-2, from those with high neutralising antibody titres and broad T-cell repertoires, to the minority with barely detectable immunity...

These very low levels of immunity after infection would be hard to equate with protection from reinfection. Furthermore, among the longitudinal studies that have investigated waning antibody levels against SARS-CoV-2, responses have been found to last for 6 months or longer; although, depending on which components of the antibody repertoire are assayed, a substantial minority serorevert to negativity...

Pick up the pace! Slow walkers four times more likely to die from COVID-19, study finds
University of Leicester | March 16, 2021

Slow walkers are almost four times more likely to die from COVID-19, and have over twice the risk of contracting a severe version of the virus, according to a team of researchers from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre...

...The analysis found slow walkers of a normal weight to be almost 2.5 times more likely to develop severe COVID-19 and 3.75 times more likely to die from the virus than normal weight fast walkers.

...A further key finding from this research was that normal weight slow walkers are more at risk for both severe COVID-19 and COVID-19 mortality than fast walkers with obesity. Furthermore, risk was uniformly high in normal weight slow walkers and slow walkers with obesity...

www.sciencedaily.com/releases/2021/03/210316083755.htm

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Thomas Yateset al. 2021. Obesity, walking pace and risk of severe COVID-19 and mortality: analysis of UK Biobank. International Journal of Obesity, Feb 26, 2021; DOI: 10.1038/s41366-021-00771-z https://www.nature.com/articles/s41366-021-00771-z

Abstract

Obesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, may also be important risk markers. This analysis includes 412,596 UK Biobank participants with linked COVID-19 data (median age at linkage = 68 years, obese = 24%, median number of comorbidities = 1). As of August 24th 2020, there were 1001 cases of severe (in-hospital) disease and 336 COVID-19 deaths. Compared to normal weight individuals, the adjusted odds ratio (OR) of severe COVID-19 in overweight and obese individuals was 1.26 ... and 1.49 ..., respectively. For COVID-19 mortality, the ORs were 1.19 ... and 1.82 ..., respectively. Compared to those with a brisk walking pace, the OR of severe COVID-19 for steady/average and slow walkers was 1.13 ... and 1.88 ..., respectively. For COVID-19 mortality, the ORs were 1.44 ... and 1.83 ..., respectively. Slow walkers had the highest risk regardless of obesity status. For example, compared to normal weight brisk walkers, the OR of severe disease and COVID-19 mortality in normal weight slow walkers was 2.42 ... and 3.75 ..., respectively. Self-reported slow walkers appear to be a high-risk group for severe COVID-19 outcomes independent of obesity.

Links between COVID-19 and skin rashes
Tim Newman | March 18, 2021

More than 1 in 5 people with a SARS-CoV-2 infection reported skin changes as the only symptom of infection.

...Of the 2,021 app users who tested positive for SARS-CoV-2, 8.8% reported skin-related changes, 6.8% reported body rashes, and 3.1% reported rashes on the hands or feet, which are called acral rashes.

The authors note that only 1.1% of this group experienced both body and acral rashes, suggesting that the two occur for different reasons, the researchers believe.

The body rashes, they theorize, might be caused by “immunological reactions to the virus,” whereas acral rashes could result from blood clots or damaged blood vessel walls.

In the group of untested symptomatic users who reported at least one of the main symptoms of COVID-19, the results were similar, with 8.2% reporting skin changes.

From the independent survey of 11,544 participants, the researchers analyzed the timing of skin changes.

According to the analysis of survey respondents who had tested positive for SARS-CoV-2 and experienced skin changes, 47% of these changes appeared at the same time as other COVID-19 symptoms. For 35% of the respondents, skin changes developed after other symptoms had started.

For 17% of the participants in this group, a rash appeared before other symptoms. And, interestingly, in 21% of participants, a rash was the only symptom.

Using the photos of the participants’ rashes, the scientists identified the most common types, which were:

papular rashes (41.2%) — small, raised bumps
urticaria (30%) — red, itchy welts
acral rashes (23.1%) — lesions on the hands or feet

Acral lesions and papular rashes lasted for an average of 13 or 14 days, respectively, and urticaria for just 5 days...

https://www.medicalnewstoday.com/articles/links-between-covid-19-and-skin-rashes

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A. Visconti et al. 2021. Diagnostic value of cutaneous manifestation of SARS‐CoV‐2 infection. British Journal of Dermatology. First published: 14 January 2021. https://doi.org/10.1111/bjd.19807 https://onlinelibrary.wiley.com/doi/10.1111/bjd.19807

Summary
Background...
Objectives...

Methods
We used data from 336 847 UK users of the COVID Symptom Study app to assess the diagnostic value of body rash or an acral rash in SARS‐CoV‐2 infection, and data from an independent online survey of 11 544 respondents to investigate skin‐specific symptoms and collect their photographs.

Results
Using data from the app, we show significant association between skin rashes and a positive swab test result (odds ratio 1·67 ...). Strikingly, among the respondents of the independent online survey, we found that 17% of SARS‐CoV‐2‐positive cases reported skin rashes as the first presentation, and 21% as the only clinical sign of COVID‐19. Together with the British Association of Dermatologists, we have compiled a catalogue of images of the most common skin manifestations of COVID‐19 from 400 individuals (https://covidskinsigns.com), which we have made publicly available to assist clinicians in recognition of this early clinical feature of COVID‐19.*

Conclusions
Skin rashes cluster with other COVID‐19 symptoms, are predictive of a positive swab test, and occur in a significant number of cases, either alone or before other classical symptoms. Recognizing rashes is important in identifying new and earlier cases of COVID‐19.

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* British Association of Dermatologists
COVID-19 Skin Patterns
https://covidskinsigns.com/

>29 margd: One of the great shortcomings of the Covid response has been the failure to better utilizate monoclonals. Many lives would be saved. The former US President is a case in point.

U.S. to Send Millions of Vaccine Doses to Mexico and Canada
Natalie Kitroeff, Maria Abi-Habib, Zolan Kanno-Youngs and Jim Tankersley | March 18, 2021

The United States plans to send millions of doses of the AstraZeneca vaccine to Mexico and Canada, the White House said Thursday, a notable step into vaccine diplomacy just as the Biden administration is quietly pressing Mexico to curb the stream of migrants coming to the border.

Jen Psaki, the White House press secretary, said the United States was planning to share 2.5 million doses of the vaccine with Mexico and 1.5 million with Canada, adding that it was “not finalized yet, but that is our aim.”

Tens of millions of doses of the vaccine have been sitting in American manufacturing sites. While their use has already been approved in dozens of countries, including Mexico and Canada, the vaccine has not yet been authorized by American regulators. Ms. Psaki said the shipments to Mexico and Canada would essentially be a loan, with the United States receiving doses of AstraZeneca, or other vaccines, in the future...

https://www.nytimes.com/2021/03/18/world/americas/usa-mexico-vaccine-coronavirus...
________________________________________________________________________

Oxford-AstraZeneca vaccine is 'safe', European drug regulator rules
Yuliya Talmazan | March 18, 2021

The Oxford-AstraZeneca Covid-19 vaccine is safe to use, the European Medicines Agency said Thursday after a number of countries, including Germany, France and Italy, suspended it over concerns about blood clots in some recipients.

Executive Director Emer Cooke told a news briefing that her agency's expert committee on the safety of medicines has “come to a clear scientific conclusion...This is a safe and effective vaccine...Its benefits in protecting people from Covid-19, with the associated risks of death and hospitalization, outweigh the possible risks.”

Cooke added that the vaccine was not associated with an increase in the overall risk of blood clots, but during the investigation the committee had seen a small number of "rare and unusual, but very serious clotting disorders," which had triggered a more focused review.

"Based on the evidence available and after days of in-depth analysis of lab results, clinical reports, autopsy reports and further information from the clinical trials, we still cannot rule out definitively a link between these cases and the vaccine" ...

The committee had therefore recommended "to raise awareness of these possible risks, making sure that they are included in the product information....drawing attention to these possible rare conditions and providing information to health care professionals and vaccinated people will help to spot and mitigate any possible side effects."

More investigations will be conducted, she said...

https://www.nbcnews.com/news/world/oxford-astrazeneca-covid-19-vaccine-safe-euro...

Nice overview of SARS-CoV-2. Amazing how much is known after just one year.


Ben Hu et al. 2021. Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology volume 19, pages141–154(2021). Published: 06 October 2020. https://www.nature.com/articles/s41579-020-00459-7

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.

Introduction
Emergence and spread
Genomics, phylogeny and taxonomy
Animal host and spillover
Receptor use and pathogenesis
Clinical and epidemiological features
Diagnosis

Therapeutics:
Inhibition of virus entry
Inhibition of virus replication
Immunomodulatory agents
Immunoglobulin therapy

Vaccines
Future perspectives
References

Catharina Boehme et al. 2021. Promoting diagnostics as a global good. Nature Medicine volume 27, pages367–368(15 March 2021). https://www.nature.com/articles/s41591-020-01215-3

The COVID-19 pandemic has reasserted the central role of effective diagnostics in the response to outbreaks. But a lack of coordination still hampers widespread access to these critical tools. A diagnostics agenda for global health is urgently needed for the promotion of diagnostics as a global good and to ensure their delivery.

Keeping diagnostics on the agenda
1. Create a diagnostics agenda for global health
2. Build diagnostics literacy...media
3. Generate roadmaps for building effective diagnostics systems in countries
4. Diversify manufacturing base for high-quality tests
5. Expand diagnostic testing beyond the health sector..wildlife

Pitfalls of politicization
Pivoting to ‘build back better’

COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets
News 18/03/2021

EMA’s safety committee, PRAC, concluded its preliminary review of a signal of blood clots in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting of 18 March 2021. The Committee confirmed that:

the benefits of the vaccine in combating the still widespread threat of COVID-19 (which itself results in clotting problems and may be fatal) continue to outweigh the risk of side effects;

the vaccine is not associated with an increase in the overall risk of blood clots (thromboembolic events) in those who receive it;

there is no evidence of a problem related to specific batches of the vaccine or to particular manufacturing sites;

however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e. low levels of blood platelets (elements in the blood that help it to clot) with or without bleeding, including rare cases of clots in the vessels draining blood from the brain (CVST).

These are rare cases – around 20 million people in the UK and EEA had received the vaccine as of March 16 and EMA had reviewed only 7 cases of blood clots in multiple blood vessels (disseminated intravascular coagulation, DIC) and 18 cases of CVST. A causal link with the vaccine is not proven, but is possible and deserves further analysis.

The PRAC involved experts in blood disorders in its review, and worked closely with other health authorities including the UK’s MHRA which has experience with administration of this vaccine to around 11 million people. Overall the number of thromboembolic events reported after vaccination, both in studies before licensing and in reports after rollout of vaccination campaigns (469 reports, 191 of them from the EEA), was lower than that expected in the general population. This allows the PRAC to confirm that there is no increase in overall risk of blood clots. However, in younger patients there remain some concerns, related in particular to these rare cases.

The Committee’s experts looked in extreme detail at records of DIC and CVST reported from Member States, 9 of which resulted in death. Most of these occurred in people under 55 and the majority were women. Because these events are rare, and COVID-19 itself often causes blood clotting disorders in patients, it is difficult to estimate a background rate for these events in people who have not had the vaccine. However, based on pre-COVID figures it was calculated that less than 1 reported case of DIC might have been expected by 16 March among people under 50 within 14 days of receiving the vaccine, whereas 5 cases had been reported. Similarly, on average 1.35 cases of CVST might have been expected among this age group whereas by the same cut-off date there had been 12. A similar imbalance was not visible in the older population given the vaccine.

The Committee was of the opinion that the vaccine’s proven efficacy in preventing hospitalisation and death from COVID-19 outweighs the extremely small likelihood of developing DIC or CVST. However, in the light of its findings, patients should be aware of the remote possibility of such syndromes, and if symptoms suggestive of clotting problems occur patients should seek immediate medical attention and inform healthcare professionals of their recent vaccination. Steps are already being taken to update the product information for the vaccine to include more information on these risks.

The PRAC will undertake additional review of these risks, including looking at the risks with other types of COVID-19 vaccines (although no signal has been identified from monitoring so far). Close safety monitoring of reports of blood clotting disorders will continue, and further studies are being instituted to provide more laboratory data as well as real-world evidence. EMA will communicate further as appropriate.

Information for patients
COVID-19 Vaccine AstraZeneca is not associated with an increased overall risk of blood clotting disorders.

There have been very rare cases of unusual blood clots accompanied by low levels of blood platelets (components that help blood to clot) after vaccination. The reported cases were almost all in women under 55.

Because COVID-19 can be so serious and is so widespread, the benefits of the vaccine in preventing it outweigh the risks of side effects.

However, if you get any of the following after receiving the COVID-19 Vaccine AstraZeneca:
breathlessness,
pain in the chest or stomach,
swelling or coldness in an arm or leg,
severe or worsening headache or blurred vision after vaccination,
persistent bleeding,
multiple small bruises, reddish or purplish spots, or blood blisters under the skin,

please seek prompt medical assistance and mention your recent vaccination.

Information for healthcare professionals
Cases of thrombosis and thrombocytopenia, some presenting as mesenteric vein or cerebral vein/cerebral venous sinus thrombosis, have been reported in persons who had recently received COVID-19 Vaccine AstraZeneca, mostly occurring within 14 days after vaccination. The majority of reports involved women under 55, although some of this may reflect greater exposure of such individuals due to targeting of particular populations for vaccine campaigns in different Member States.

The number of reported events exceeds those expected, and causality although not confirmed, cannot therefore be excluded. However, given the rarity of the events, and the difficulty of establishing baseline incidence since COVID-19 itself is resulting in hospitalisations with thromboembolic complications, the strength of any association is uncertain.

EMA considers that the benefit-risk balance of the medicine remains positive, and there is no association with thromboembolic disorders overall. However, steps will be taken to update the SmPC and package leaflet with information on cases of DIC and CVST that have occurred.

Healthcare professionals are urged to be alert for possible cases of thromboembolism, DIC or CVST occurring in vaccinated individuals.

Recipients should be warned to seek immediate medical attention for symptoms of thromboembolism, and especially signs of thrombocytopenia and cerebral blood clots such as easy bruising or bleeding, and persistent or severe headache, particularly beyond 3 days after vaccination.

A direct healthcare professional communication (DHPC) will be sent to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website...

https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-ou...

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EU Medicines Agency @EMA_News | 3:00 PM · Mar 18, 2021
Did you miss our press briefing on the conclusion of the review of #COVID19Vaccine AstraZeneca and blood clots? You can watch it on EMA’s YouTube channel:

EMA press conference (46:47)
European Medicines Agency | 3/18/2021
https://www.youtube.com/watch?v=qYmP02SIQNI
______________________________________________

Europe's clearing of the #AstraZeneca #vaccine is good news for the world. But what's still needed is the data behind the initial concerns. "The transparency problem is a big one, says Dr @EricTopol. Meanwhile, the issue could impact vaccine hesitancy, already a problem globally.

5:37 ( https://twitter.com/holmescnn/status/1372766592308637706 )

- Michael Holmes @holmescnn | 12:27 AM · Mar 19, 2021

A Traveler’s Worst Nightmare: When Your Covid-19 Test Comes Back Positive
Karen Schwartz | March 17, 2021

Contracting the coronavirus while far from home is a frightening possibility. And sometimes it happens, with consequences that can be deadly...

https://www.nytimes.com/2021/03/17/travel/covid-test-positive-vacation.html

US House Committee on Foreign Affairs
A Year Out: Addressing International Impacts of the COVID-19 Pandemic
March 18, 2021 2:30 PM

02:56:10 https://youtu.be/sO1C_ZmQseE
(Video commences at 00:09:30)

Witnesses

Ashish Jha, M.D.
Dean, Brown University School of Public Health

Ms. Tjada D’Oyen McKenna
Chief Executive Officer, Mercy Corps

Mr. Tom Bollyky
Senior Fellow, Council on Foreign Relations
Tweet: https://twitter.com/TomBollyky/status/1372849695459049474

Ms. Penny Naas
President, International Public Affairs and Sustainability
United Parcel Service
Documents

Hearing notice

https://foreignaffairs.house.gov/hearings?ID=C5FFC3CB-D689-41AD-A5CD-5641C3DE378...
Permalink: https://foreignaffairs.house.gov/2021/3/a-year-out-addressing-international-impa...

Angela L. Rasmussen and Saskia V. Popescu. 2021. SARS-CoV-2 transmission without symptoms (Perspective). Science 19 Mar 2021: Vol. 371, Issue 6535, pp. 1206-1207 DOI: 10.1126/science.abf9569 https://science.sciencemag.org/content/371/6535/1206

...With many contagious people experiencing no symptoms and in the absence of robust surveillance testing for asymptomatic or presymptomatic infections, it is critical to maximize efforts to reduce transmission risk in the community...infection prevention efforts should focus...on the additive nature of risk reduction and the need for continued vigilance in community-based infection prevention measures, including masks, distancing, avoiding enclosed spaces, ventilation, hand hygiene, and disinfection...

Graph--symptomatic/asymptomatic viral replication & symptom onset ( https://twitter.com/EricTopol/status/1372608901967876096/photo/1 )

Article highlighted by Topol ( https://twitter.com/EricTopol/status/1372608901967876096/photo/2 )

COVID-19 in Brazil: Developments, Warnings and Lessons
March 18, 2021

Main message: Brazil is being hit hard by the COVID-19 pandemic again. After experiencing a large first wave of cases and deaths nine months ago, Brazil is now in the throes of a second wave that is overwhelming its health care system. The epidemic in Brazil has displayed a devastating synergy: weak mitigation measures fueled the emergence and spread of a more transmissible variant of SARS-CoV-2, the virus that causes COVID-19. COVID-19 vaccines are now available, but the rollout in Brazil has been slow. The full range of available mitigation measures, including vaccines and both individual and societal public health and social measures (PHSMs), is necessary to control the epidemic and limit its local and global impact.

The COVID-19 epidemic in Brazil

The COVID-19 epidemic in the State of Amazonas

What fueled the second wave in Amazonas and across Brazil?
1. The emergence of the P.1 variant
2. The failure of mitigation measures to sufficiently suppress transmission of SARS-CoV-2

The synergistic effects of the emergence of the P.1 variant and insufficient mitigation measures

Given the current state of the COVID-19 epidemic in Brazil, what can be done?

...Multiple coordinated and targeted strategies are needed to curb COVID-19 cases and deaths in Brazil. Rapid rollout of COVID-19 vaccines is necessary to protect the most vulnerable people as quickly as possible and to prevent future epidemic surges. At the subnational level, critical efforts are being made to mitigate the spread and impact of the epidemic. But more stringent, coordinated PHSMs targeted to areas with high levels of transmission may be necessary, at least in the short term. Ideally, financial and social support that allows the population to adhere to mitigation measures should come with those measures. If transmission is not reduced, it is not just Brazilians at risk: a surging epidemic poses a serious threat to both local and global populations. The World Health Organization reports that the P.1 variant has been found in 32 countries to date, and the U.S. CDC has reported at least 17 cases in 10 U.S. locations. According to the Director General of the World Health Organization, “If Brazil is not serious, then it will continue to affect all of the neighborhood there — and beyond…This is not just about Brazil. It’s about the whole Latin America, and even beyond.”

https://preventepidemics.org/covid19/science/weekly-science-review/march-3rd-17t...

Eric Feigl-Ding @DrEricDing | 6:13 AM · Mar 19, 2021
Vaccination alone cannot contain #COVID19 if immediately relaxing all other mitigations, says study.
Only *gradual release* of control measures + high vaccine uptake + high efficacy vaccine can together to minimize future waves.
DO NOT RELAX TOO FAST!
https://thelancet.com/action/showPdf?pii=S1473-3099%2821%2900143-2 *
Image (https://twitter.com/DrEricDing/status/1372853841037770752/photo/1)
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"our predictions highlight the risks associated with early or rapid relaxation of NPIs"

* Sam Moore et al. 2021. Vaccination and non-pharmaceutical interventions for COVID-19: a mathematical modelling study. Lancet Infect Dis 2021(Published Online March 18, 2021) https://doi.org/10.1016/ S1473-3099(21)00143 https://www.thelancet.com/action/showPdf?pii=S1473-3099%2821%2900143-2

Summary...
Findings
We estimate that vaccination alone is insufficient to contain the outbreak. In the absence of NPIs (non-pharmaceutical interventions), even with our most optimistic assumption that the vaccine will prevent 85% of infections, we estimate R to be 1·58 ... once all eligible adults have been offered both doses of the vaccine. Under the default uptake scenario, removal of all NPIs once the vaccination programme is complete is predicted to lead to 21400 deaths ... due to COVID-19 for a vaccine that prevents 85% of infections, although this number increases to 96700 deaths ... if the vaccine only prevents 60% of infections. Although vaccination substantially reduces total deaths, it only provides partial protection for the individual; we estimate that, for the default uptake scenario and 60% protection against infection, 48·3% ... and 16·0% ... of deaths will be in individuals who have received one or two doses of the vaccine, respectively.

Interpretation
For all vaccination scenarios we investigated, our predictions highlight the risks associated with early or rapid relaxation of NPIs. Although novel vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake, both of which need to be carefully monitored.

...Discussion....

GMT — UK faces vaccine shortfall
Medical News Today | 03/19/2021

Due to production and testing issues, the United Kingdom is facing a shortfall in vaccine supplies. This setback will delay shots for people under 50, and these may now be pushed back until May.

Speaking with the BBC, Dr. Martin Marshall, chairman of the Royal College of General Practitioners says, “It was disappointing news when we heard yesterday that the supplies weren’t going to be available during April. It’s a massively successful program overall, and this is a bit of a setback.”

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

‘It’s a very special picture.’ Why vaccine safety experts put the brakes on AstraZeneca’s COVID-19 vaccine
Gretchen Vogel, Kai Kupferschmidt | Mar. 17, 2021

...symptoms seen in at least 13 patients, all between ages 20 and 50 and previously healthy, in at least five countries are more frequent than would be expected by chance. The patients, at least seven of whom have died, suffer from widespread blood clots, low platelet counts, and internal bleeding—not typical strokes or blood clots. “It’s a very special picture” of symptoms, says Steinar Madsen, medical director of the Norwegian Medicines Agency. “Our leading hematologist said he had never seen anything quite like it.”

...The United Kingdom, which has administered the AstraZeneca vaccine to more than 10 million people, has so far not reported similar clusters of unusual clotting or bleeding disorders.

...(Steinar Madsen, medical director of the Norwegian Medicines Agency) believes the unusual symptoms may be the result of “a very strong immunological reaction.” ...It’s possible, (Clemens Wendtner, a hematology and infectious disease specialist at the Munich Clinic, Schwabing) says, that the unusual cases had a COVID-19 infection before they got vaccinated; many were health care workers and teachers who may have been exposed at work. Coming on top of the infection, the vaccine might somehow have triggered an overreaction by the immune system, sparking the clotting syndrome. (Arnold Ganser, a hematologist at Hannover Medical School) thinks patients suffering from CVT (cerebral venous thrombosis) may be the tip of the iceberg and that more people may suffer similar, but milder, symptoms.

If there really is a link between the vaccine and the blood disorders, (Robert Brodsky, a hematologist at Johns Hopkins University) says a lot of evidence points to a crucial role for the complement system. Dysregulation of that system can lead to diseases that Brodsky terms “complemenopathies.” “What complementopathies have in common is: They all have thrombosis as part of it, they all have thrombocytopenia as part of it, they all have relative resistance to traditional anticoagulants and they all have triggers such as infections, inflammation, pregnancy, cancer, vaccines.”

...(unlikely) that specific batches of the vaccine caused the problem

...Paul Hunter, an infectious disease expert at the University of East Anglia, noted in a statement that even if the risk of CVT is raised by the vaccine to five or more cases per million people vaccinated, the COVID-19 infection fatality rate for men in their mid-40s is 0.1%, or 1000 deaths per million infected.

Given the rarity of the syndrome and the vaccine’s enormous benefits, it might be worth restarting immunizations even if the complications are connected to the vaccine, but with precautions, (Klaus Cichutek, head of Paul Ehrlich Institute (PEI), Germany’s agency in charge of vaccine safety) says, such as informing people about what to do if certain symptoms appear or excluding some groups of people from the vaccinations...

https://www.sciencemag.org/news/2021/03/it-s-very-special-picture-why-vaccine-sa...

Eric Topol @EricTopol | 4:29 PM · Mar 20, 2021
https://twitter.com/EricTopol/status/1373371224940634113
The Astra-Zeneca vaccine and rare clotting events

1. Cause (but German transfusion med prof says rare + they now know how to treat)
https://wsj.com/articles/scientists-say-they-found-cause-of-blood-clotting-linke...
by @bopanc
Image https://twitter.com/EricTopol/status/1373371224940634113/photo/1

2. Ethics
https://nytimes.com/2021/03/19/world/europe/europe-vaccine-astrazeneca-interpret...
by @Max_Fisher
Image https://twitter.com/EricTopol/status/1373371224940634113/photo/2

3. It's not over--more cases in Denmark
https://nytimes.com/live/2021/03/20/world/covid-19-coronavirus?type=styln-live-u...
@LMSTErichsen
Inline image https://twitter.com/EricTopol/status/1373371224940634113/photo/3
Image https://twitter.com/EricTopol/status/1373371224940634113/photo/4

Argument for cheap, easily available, home tests to reduce transmission:
"Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (more than 95%) for identifying infected individuals."

Rebecca L Smith et al. 2021. Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. MedRxiv (March 20, 2021) doi: https://doi.org/10.1101/2021.03.19.21253964 https://www.medrxiv.org/content/10.1101/2021.03.19.21253964v1

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

Abstract
What is already known about this topic? Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period.

What is added by this report? We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency.

What are the implications for public health practice? RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed more than 94% sensitivity to detect infection if used at least twice per week.

...Table 2: Daily sensitivity of each test platform by day relative to the day of first nasal swab viral culture positivity

...Table 3: Protocol sensitivity of each test platform to detect an infected person during a 14-day testing period, relative to the frequency of testing.

...Discussion
...We found that all three diagnostic tests demonstrated a high degree of daily sensitivity during the presumed infectious period, but that the RTqPCR tests exhibited superior daily sensitivities prior to this period. Our data suggest that RTqPCR tests
can be more effective than antigen tests at mitigating community spread of SARS-CoV-2, but only if the turnaround time for
RTqPCR results is short. Finally, these data also quantitatively demonstrate the importance of frequent (at least twice per
week) screening to maximize likelihood of detecting infected individuals regardless of testing modality.

The United States of America has a medical community, quality of medical education, a quantity of large hospitals; and yet we are reported as having a vastly disproportionate amount of the infections. If the total number of deaths do not go up in exactly the same number as the number of COVID deaths, there is no reason to blame everything on a virus practically all medical personnel are identifying by footprints only. Lead poisonings mimic flu-like symptoms. Meningitis, food poisoning, hepatitis and HIV can result in flu-like symptoms. Why did all drug houses smoking recreational drugs not die? Why are there still prostitutes alive at all in the US? Why are the mythical asymptomatic, contagious people targets needing restraint? Millions died for freedoms that some people demand be eradicated now.

Are all people disinfecting their shoes in a clean room/outbuilding? Are people wearing footies and sterile galoshes to ferry children to and from school? Have people invested in more skylights, since UV light kills bacteria? Have people called SWAT Environmental to install UV lights into the ductwork of their AC/HVAC systems for the same reason? If the answers are largely 'no', why not?

>48 smirks4u: We’ve now had over a year to understand the matter. SARS-CoV-2 is primarily a respiratory pathogen. Disinfecting shoes, footies, galoshes are of practically zero value. Bacteria have nothing to do with this situation, as we are dealing with a virus not a bacterium. No reason to focus on things that don’t work because we know what works. The important thing is preventing respiratory transmission, which means masks, distance, avoid large gatherings. Need particular caution indoors in a shared airspace. And get vaccinated. Thankfully none of this is a mystery now.

U.S. production of COVID-19 vaccine dramatically speeds up
March production expected to be almost triple that of February
Peter Loftus | March 21, 2021

...Pfizer figured out how to stretch scarce supplies of special filters needed for the vaccine production process by recycling them. Moderna shortened the time it needed to inspect and package newly manufactured vials of its vaccine.

The companies—along with Johnson & Johnson JNJ, -0.27%, which recently launched a Covid-19 vaccine—also are teaming up with other firms to further increase production.

In addition, the U.S. government has helped vaccine makers access supplies under the Defense Production Act...($105 million) help Merck & Co...make doses of J&J’s COVID-19 vaccine...

https://www.marketwatch.com/story/u-s-production-of-covid-19-vaccine-dramaticall...

___________________________________________________

Brazil Seeks to Import Excess US Coronavirus Vaccines
VOA News | March 20, 2021

...The talks between the U.S. and Brazil began March 13. On Friday, the U.S. said it was lending 4 million doses of the AstraZeneca vaccine to Canada and Mexico but did not mention Brazil...

...Brazil is second behind the U.S. in the number of coronavirus cases, nearly 12 million since the pandemic began, and deaths, nearly 293,000.

President Jair Bolsonaro, who famously told his country to "stop whining" about the country's death from "a little flu," has signed three measures to speed the purchase of vaccines, including those from Pfizer-BioNTech and Johnson & Johnson...

https://www.voanews.com/covid-19-pandemic/brazil-seeks-import-excess-us-coronavi...

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Happily, vaccine AstraZeneca vaccine is reportedly effective against P1, first reported in Brazil:
https://www.reuters.com/article/us-health-coronavirus-brazil-variant-idUSKBN2B02...

Wonder why there is any "negotiation", given the severity of Brazil's COVID situation:
Lead with Canada and Mexico "loans", to prepare US public opinion?
Ensure that Brazil's Bolsonaro Administration will distribute vaccines responsibly?
Screw-ups would not only hurt Brazilians even more, but could prejudice American public opinion against future sharing...

Good news from trial requested by US:
2 standard doses of Oxford-AstraZeneca vaccine is effective, and for over 65s and diverse peoples.
Safe for 32.5K participants (but too few to pick up the very rare serious blood clots?).
No mention of smaller first dose strategy?

AstraZeneca’s U.S. trial shows coronavirus vaccine is 79 percent effective
William Booth and Carolyn Y. Johnson | March 22, 2021

...easily transported $4 shot...

...The trials included 32,449 adult participants in all age groups, most of them in the United States. The volunteers received either two standard doses of the Oxford-AstraZeneca vaccine or a placebo, at a four-week interval, the researchers said.

The scientists said the data show the vaccine is 79 percent effective against symptomatic covid-19, the disease caused by the coronavirus, and 100 percent effective against severe illness. There were five cases of severe illness in the trial, all of them in the group that received a placebo.

This is considerably higher than the Oxford-AstraZeneca trials in Britain last year, which showed 62 percent efficacy.

The company said in its release it will apply for emergency authorization from the Food and Drug Administration “in the coming weeks,” but a question that has emerged recently is whether the United States, which President Biden has promised will have enough vaccine for all adults by the end of May, will need the vaccine. Fauci said it was too soon to know how it would fit into the U.S. vaccine portfolio

“The one thing that one can say for sure, that this is good for the world, because it’s a cheap vaccine. It’s got good results. They will likely be able to produce enough for a lot of different countries,” Fauci said.

The Oxford researchers said that the Data and Safety Monitoring Board in the United States “reported no safety concerns among the participants receiving at least one dose of the vaccine.”

The results were reported in a pair of brief news releases from the pharmaceutical company and the university scientists.

...The U.S. government has preordered 300 million doses of the AstraZeneca vaccine.

If the Oxford-AstraZeneca shot is approved by the FDA for emergency use, it would offer the United States a bounty of vaccines — either to administer to U.S. citizens or provide to needy countries around the world. Most nations have not administered a single dose of any vaccine.

...In its first set of clinical trials in Britain, South Africa and Brazil, AstraZeneca was criticized for its failure to include enough elderly volunteers to show the vaccine works well in those most at risk of serious illness. In the current U.S. trials, about 20 percent of participants were 65 years and over, and approximately 60 percent had health conditions that can make covid more life-threatening, such as diabetes, severe obesity or cardiac disease.

The U.S. trials also sought to be representative of the population. AstraZeneca said 79 percent were White or Caucasian, 8 percent Black, 4 percent Native American and 4 percent Asian; in addition, 22 percent of participants were Hispanic...

https://www.washingtonpost.com/world/europe/astrazeneca-vaccine-trial-efficacy/2...
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NEWS RELEASE:
ZD1222 US Phase III trial met primary efficacy endpoint in preventing COVID-19 at interim analysis
AstraZeneca | 22 March 2021

79% vaccine efficacy at preventing symptomatic COVID-19

100% efficacy against severe or critical disease and hospitalisation

Comparable efficacy result across ethnicity and age,
with 80% efficacy in participants aged 65 years and over

Favourable reactogenicity and overall safety profile...

https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-us-vacc...

Navajo Nation has reported 0 new COVID-19 cases for the first time in six months!!!!!

- Arlyssa Becenti (Navajo Times) @ABecenti | 7:28 PM · Mar 22, 2021

Whoa?? Another insight perhaps on US willingness to share AstraZeneca vaccines? US may well approve in the end, but further delay and uncertainty means US may not need--and Americans might become Astrazeneca-shy? Globally, people could die if they choose COVID over AstraZeneca. In long term it's good if US vaccine authorities are playing straight. Could AstraZeneca be that ham-handed/short-sighted with its reputation? (Earlier study design, current reporting?) Have rare clot reports so unnerved them?

U.S. health officials question results from AstraZeneca’s vaccine trial, less than a day after they came out.
Rebecca Robbins and Sheila Kaplan | March 23, 2021

...Federal health officials said early Tuesday that results from a U.S. trial of AstraZeneca’s Covid-19 vaccine may have relied on “outdated information” that “may have provided an incomplete view of the efficacy data”... data and safety monitoring board, an independent panel of medical experts under the National Institutes of Health that has been helping to oversee AstraZeneca’s U.S. trial, had notified government agencies and AstraZeneca late Monday that it was “concerned” by information the company had released that morning.

The institute urged AstraZeneca to work with the monitoring board “to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”

...Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said it was “highly irregular” to see such a public display of friction between a monitoring board and a study sponsor, which are typically in close concordance.

“I’ve never seen anything like this,” he said in an interview after the institute’s statement was released. “It’s so, so troubling.”

AstraZeneca’s relationship with the U.S. authorities has been fraught since last year, when senior health officials believed the company was not being forthright about the design of its clinical trials, its results and safety issues. That skepticism carried over to last week, when senior officials at a number of federal health agencies grew suspicious about why AstraZeneca had not announced data from its U.S. study.

That U.S. trial, which involved more than 32,000 participants, was the largest test of its kind for the shot. The results AstraZeneca released on Monday were from an interim look at the data after 141 Covid-19 cases had turned up among volunteers.

The company did not disclose how up-to-date the data are. If the analysis was conducted on data from a month or two ago, it is possible that a more current look would present a different picture of the vaccine’s effectiveness and safety. The company has said it will provide the Food and Drug Administration with a more comprehensive, recent set of data than what it disclosed on Monday...

https://www.nytimes.com/2021/03/22/world/us-health-officials-question-results-fr...

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NIAID Statement on AstraZeneca Vaccine
News Release | Tuesday, March 23, 2021
https://www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccin...

A British study, not yet peer-reviewed, found that cancer patients required two doses of the Pfizer (mRNA) vaccine in order to fully protect themselves and their community. Immune-compromised people who cannot fully suppress the virus can be fertile ground for selection--and spread--of deleterious mutations.

Leticia Monin-Aldama et al. 2021. Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech mRNA) for cancer patients in the context of the UK vaccine priority guidelines.doi: https://doi.org/10.1101/2021.03.17.21253131 MedRxiv March 17, 2021. https://www.medrxiv.org/content/10.1101/2021.03.17.21253131v1

This article is a pre-print and has not been peer-reviewed.

...in contrast to its very high performance in healthy controls (>90 margd:% efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn...

Eric Topol @EricTopol | 11:06 PM · Mar 22, 2021

While there haven't been vaccine clinical trials directed vs P.1 (Brazil), the data we have for this variant (along w/ B.1.351, S Africa, which has more immune evasion potential) from mRNA vaccinee serum supports preserved efficacy

https://nejm.org/doi/full/10.1056/NEJMc2102017?query=featured_home

https://cell.com/cell/pdf/S0092-8674(21)00367-6.pdf_returnURL=https%3A%2F%2Flink...

Image ( https://twitter.com/EricTopol/status/1374195935140454405/photo/1 )
Image ( https://twitter.com/EricTopol/status/1374195935140454405/photo/2 )
Image ( https://twitter.com/EricTopol/status/1374195935140454405/photo/3 )
Image ( https://twitter.com/EricTopol/status/1374195935140454405/photo/4 )

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

Yang Liu et al. 2021. Neutralizing Activity of BNT162b2-Elicited Serum (Correspondence). NEJM (March 8, 2021) DOI: 10.1056/NEJMc2102017 https://www.nejm.org/doi/full/10.1056/NEJMc2102017 https://www.nejm.org/doi/full/10.1056/NEJMc2102017

A preliminary version of this letter was published on February 17, 2021
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Hoffmann, M. et al. 2021. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies, Cell (2021), doi: https://doi.org/10.1016/j.cell.2021.03.036 . Journal pre-proof: https://www.cell.com/cell/pdf/S0092-8674(21)00367-6.pdf

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, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (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 all variants into human cells is susceptible to blockade by the entry inhibitors soluble ACE2, Camostat, EK-1 and EK-1-61 C4. In contrast, entry of the B.1.351 and P.1 variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment. Moreover, entry of these variants was less efficiently inhibited by plasma from convalescent COVID-19 64 patients and sera from BNT162b2 vaccinated individuals. These results suggest that SARS-65 CoV-2 may escape neutralizing antibody responses, which has important implications for efforts to contain the pandemic.

>50 margd: contd AstraZeneca efficacy against P1, first reported in Brazil :)

Mellanie Fontes-Dutra, PhD @mellziland | 11:13 PM · Mar 22, 2021:
https://twitter.com/mellziland/status/1374197508461764612

AstraZeneca's vaccine demonstrated mild impact by P.1 in neutralizing antibody's titers.
Good for us in Brazil, which is vaccinating with it.
Expecting the clinical trials directed by P.1 evaluating efficacy and T cell response as well.

Mellanie Fontes-Dutra, PhD @mellziland · Mar 17
AstraZeneca: Os títulos de neutralização contra P.1 foram reduzidos 2,9 vezes.
Image ( https://twitter.com/mellziland/status/1372387226210947072/photo/1 )

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Eric Topol @EricTopol | 12:06 AM · Mar 23, 2021

These data are highly encouraging.
"We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351"

Thanks so much for bringing this to my attention, which extends the solid data from mRNA vaccines to AZ vs P.1
Image ( https://twitter.com/EricTopol/status/1374211026015510536/photo/1 )

Leprosy drug may help fight COVID-19
Robby Berman | March 21, 2022

In an effort to combat SARS-CoV-2, and with the rise of other coronaviruses likely, experts are looking for existing drugs that can fight these infections.

A leprosy drug called clofazimine has shown promise against SARS-CoV-2 in hamsters.

Clofazimine blocks the ability of SARS-CoV-2 to enter cells and replicate via RNA.

The drug has also shown promise against Middle East respiratory syndrome (MERS) in laboratory experiments...

https://www.medicalnewstoday.com/articles/leprosy-drug-may-help-fight-covid-19

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Shuofeng Yuan et al. 2021. Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Nature (March 16, 2021) https://www.nature.com/articles/s41586-021-03431-4

Abstract
COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) since 2012... Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profile..., possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 and MERS-CoV replication in multiple in vitro systems. The FDA-approved molecule was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and faecal viral shedding, and also mitigated inflammation associated with viral infection. Combinatorial application of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted upper respiratory tract viral shedding. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, and, possibly most importantly, emerging CoVs of the future.

https://www.huffpost.com/entry/anthony-fauci-childrens-book-debut_n_60597534c5b6...
Anthony Fauci Stars In An Eye-Popping Biography For Kids
“He was a kid with a million questions.”

“Dr. Anthony Fauci: How a Boy from Brooklyn Became America’s Doctor” will be released by Simon & Schuster at the end of June. The book, written by Kate Messner and illustrated by Alexandra Bye, features tidbits from Fauci’s life and colorful illustrations

Global COVID-19 vaccine summary: Side effects
MNT News Team | March 23, 2021

Currently, in various areas of the world, 13 COVID-19 vaccines have been authorized for use. In this feature, we look at the types and their reported side effects.

...Each of the following vaccines has received use authorization in at least one country.

Name Manufacturer Type of vaccine Efficacy rate
BNT162b2 Pfizer-BioNTech mRNA 95%
mRNA-1273 Moderna mRNA 94.5%
Ad26.COV2.S Janssen (J&J) Viral vector 66%
AZD1222 Oxford-AstraZeneca Viral vector 81.3%
Covishield* Serum Institute of India Viral vector 81.3%
Ad5-nCov CanSino Viral vector 65.28%
Sputnik V Gamaleya Viral vector 91.6%
Covaxin Bharat Biotech Inactivated 80.6%
BBIBP-CorV Sinopharm (Beijing) Inactivated 79.34%
Inactivated (Vero Cell) Sinopharm (Wuhan) Inactivated 72.51%
CoronaVac Sinovac Inactivated 50.38%
RBD-dimer Anhui Zhifei Longcom Protein subunit Unknown
EpiVacCorona FBRI Protein subunit Unknown...

Currently, in various areas of the world, 13 COVID-19 vaccines have been authorized for use. In this feature, we look at the types and their reported side effects.

https://www.medicalnewstoday.com/articles/global-covid-19-vaccine-summary-side-e...

Rich Countries Signed Away a Chance to Vaccinate the World
Selam Gebrekidan and Matt Apuzzo | March 21, 2021

...Growing numbers of health officials and advocacy groups worldwide are calling for Western governments to use aggressive powers — most of them rarely or never used before — to force companies to publish vaccine recipes, share their know-how and ramp up manufacturing. Public health advocates have pleaded for help, including asking the Biden administration to use its patent to push for broader vaccine access.

Governments have resisted. By partnering with drug companies, Western leaders bought their way to the front of the line. But they also ignored years of warnings — and explicit calls from the World Health Organization — to include contract language that would have guaranteed doses for poor countries or encouraged companies to share their knowledge and the patents they control.

...In 2016, while working on Middle East Respiratory Syndrome, another coronavirus known as MERS, (National Institutes of Health scientist named Dr. Barney Graham) and his colleagues developed a way to swap a pair of amino acids in the coronavirus spike protein. That bit of molecular engineering, they realized, could be used to develop effective vaccines against any coronavirus. The government, along with its partners at Dartmouth College and the Scripps Research Institute, filed for a patent, which will be issued this month.

When Chinese scientists published the genetic code of the new coronavirus in January 2020, Dr. Graham’s team had their cookbook ready.

...Exactly who holds patents for which vaccines won’t be sorted out for months or years. But it is clear now that several of today’s vaccines — including those from Moderna, Johnson & Johnson, Novavax, CureVac and Pfizer-BioNTech — rely on the 2016 invention. Of those, only BioNTech has paid the U.S. government to license the technology. The patent is scheduled to be issued March 30.

Patent lawyers and public health advocates say it’s likely that other companies will either have to negotiate a licensing agreement with the government, or face the prospect of a lawsuit worth billions. ...

This gives the Biden administration leverage to force companies to share technology and expand worldwide production, said Christopher J. Morten, a New York University law professor specializing in medical patents. (manufacturers from Canada to Bangladesh say they can make vaccines — they just lack patent licensing deals)

...Dr. Graham, the N.I.H. scientist whose team cracked the coronavirus vaccine code for Moderna, said that pandemic preparedness and vaccine development should be international collaborations, not competitions.

https://www.nytimes.com/2021/03/21/world/vaccine-patents-us-eu.html

Down the way, restrictions on vaccines, PPE, tests, etc. will probably affect multi-lateral trade agreements.
What country will rely on others, for crucial supplies, including foodstuffs?

EU Set to Tighten Vaccine Export Rules Amid U.K. Tensions
Nikos Chrysoloras and Viktoria Dendrinou | March 23, 2021

European Union vaccine shipments to the rest of the world could face severe disruptions under tougher rules set to be unveiled on Wednesday.

The EU’s current export regime guarantees that supplies to some 90 countries won’t be interrupted, and also offers protection to companies like Pfizer Inc. and Moderna Inc. that have met their commitments in Europe. Under stricter restrictions being drafted in Brussels, both of those exemptions could be removed, a senior EU official said.

That could hit countries from the Gulf to Canada, as the EU is one of the world’s biggest coronavirus vaccine producers. The move marks a fresh escalation in the EU’s battle to secure supplies. The bloc’s executive arm could potentially block all exports to countries that do not reciprocate, with the U.K a prime target.

The new rules won’t affect shipments for Covax, a global program to help lower-income nations get vaccines.

https://www.bloomberg.com/news/articles/2021-03-23/eu-to-scrap-country-exemption...

Flu Shots Are Linked to a Drop in COVID-19 Infections, And Scientists Aren't Sure Why
PETER DOCKRILL | 24 MARCH 2021

...It might not actually reflect a mechanism of the flu vaccine, researchers say, so much as an effect of bias in the data, due to the behavior of people who choose to get vaccinated. But in truth we just don't know for sure.

...In the Michigan study, patients who had a flu shot were also less likely to require hospitalization and the assistance of ventilators. In other studies, having or not having a flu vaccination appears to affect mortality risk too, although that wasn't seen here.

...The researchers speculate a plausible immunologic mechanism could be a process called trained immunity, in which exposure to pathogens (in this case, in vaccine form) hypothetically primes the immune system to respond to other threats... 'heterologous immunity'...

"...Even if the direct link between the prevention of COVID-19 and the influenza vaccine is minimal...vaccination will preserve healthcare resources for those with COVID-19."

https://www.sciencealert.com/flu-shots-linked-to-drop-in-covid-19-infections-and...

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Anna Conlon et al. 2021. Impact of the influenza vaccine on COVID-19 infection rates and severity. The American Journal of Infection Control (February 22, 2021) DOI:https://doi.org/10.1016/j.ajic.2021.02.012 https://www.ajicjournal.org/article/S0196-6553(21)00089-4/fulltext

Highlights

• With vaccines against COVID-19 not yet broadly available, there is interest in assessing the role of the influenza vaccine in COVID-19 susceptibility and severity.
• The odds of testing positive for COVID-19 was reduced in patients who received an influenza vaccine compared to those who did not by 24%.
• Vaccinated patients testing positive for COVID-19 were less likely to require hospitalization or mechanical ventilation and had a shorter hospital length of stay.
• The influenza vaccine should be promoted to reduce the burden of COVID-19.

https://www.sciencealert.com/flu-shots-linked-to-drop-in-covid-19-infections-and...

This Small Country Is Way Ahead in the Covid-19 Vaccine Race
Chile lined up shots early and faced little antivaccine sentiment
Kejal Vyas | March 10, 2021

Chile is advancing a vaccination campaign against Covid-19 that is outpacing not only its Latin American neighbors but much of the world, putting the South American nation on course to become the first developing country to achieve herd immunity.

More than 22% of Chile’s 19 million people have already received at least one dose...In the past week, Chile has administered 1.06 doses per 100 inhabitants, on par with Israel, and more than any other country. The government expects to cover 80% of its people by June...

https://www.wsj.com/articles/chile-races-ahead-of-much-of-the-world-in-covid-19-...

Kenya 'runs out of ICU beds' amid Covid surge
Mercy Juma | 13:05 23 Mar

Kenya has run out of ICU beds as the country deals with a surge in Covid-19 cases, the doctors' union has said.

Healthcare workers were among those admitted at various hospitals across the country, Kenya Medical Practitioners Pharmacists and Dentists Union (KMPDU) said in a statement.

Several doctors have been sharing their experiences on social media, describing heart-breaking scenes they are witnessing in hospitals across the country.

Kenya's Director General for Health, Patrick Amoth, told a media briefing on Tuesday that a national study had found the presence of coronavirus variants first detected in South Africa and the UK.

"Most (cases) of the South African variant have been picked from our border with Tanzania, especially in people with a history of travel from Tanzania," Dr Amoth said.*

A recent study found Kenya has about 537 ICU beds and just under 300 ventilators.

The country has reported 122,000 Covid-19 cases and 2,000 deaths.

https://www.bbc.com/news/topics/c40rjmqdlzzt/kenya

* Citizen TV Kenya @citizentvkenya | 9:52 AM · Mar 23, 2021:
https://twitter.com/citizentvkenya/status/1374358445764317189
3:44 (Dr. Patrick Amoth on genomic sequencing)

Paraguay says offers of Chinese Vaccines Tied to Dumping Taiwan
Chris Horn | March 24, 2021

(Paywall)

https://www.bloomberg.com/news/articles/2021-03-24/paraguay-says-offers-of-chine...

>49 stellarexplorer: Viruses 'eat' bacterium, among other things. Touching your shoes is cross contamination. How many viruses can you put on my size twelves? "None of this is a mystery now"? We have listened to people that we Know, people we can prove, were not using a scanning electron microscope to verify a pathogen presence, much less the progression or proximate cause of death. People who have 'had' the disease have tested negative. People in total seclusion, with no symptoms, have tested positive. There is a little more than sheer disingenuousness when it comes to what a virus is and is not. Use UV lights in all HVAC systems. It's $300 to save your family's life. It's $1000 for a church daycare, or a small restaurant or business airspace.

>67 smirks4u: You're not making a lot of sense by just throwing what may or may not be facts out there without explaining how they relate to some kind of point. But I can respond to a couple of those non facts.

Viruses do attack bacteria but they aren't the same viruses that infect people. Also, you don't seem to understand that it takes a certain viral load to infect someone. One virus won't do it.

>68 jjwilson61: Mr. Wilson, viruses attack bacteria, fungi, and other cells. All of those things are in you. Your mostly-water weight body, is comprised of myriads of bacteria, fungi, viruses and their various recombinant food sources. No, one virus will not cause an infection; but most organisms grow at an exponential (J-curve graph theory) rate. If forty million viruses from the air fall to the floor/ground and my shoes bring them to an enclosed airspace; I don't think that is some huge leap of extrapolation to deduce that cross-contamination has occurred. If a sperm is the size of a double-decker bus, a virus is smaller than a moped. If you cannot breathe through a condom or a scuba diver's wet suit; your lungs cannot pump sufficient oxygen through a virus-preventive porosity. Saying that virus transmission mostly occurs when a mask is absent is sheer madness, and the medical community has people who know this.
The total death rate definitely did not increase, consequent to the supposedly additional numbers of Covid deaths. The statistical input was chicken crap, and one cannot make chicken salad out of that.

>69 smirks4u: Show me your degree in epidemiology and I'll believe that you know what you're talking about.

Low-dose "baby" aspirin may reduce mechanical ventilation, ICU admission, and in-hospital mortality of hospitalized COVID patients. Administered within 24h of hospitalization (for ~six days), although some patients also self-administered during seven days prior to hospitalization. No increase in in major bleeding or overt thrombosis. A larger clinical study will be necessary to confirm the findings.

Aspirin may reduce deaths in severe COVID-19
James Kingsland on March 23, 2021

Many people who are hospitalized with COVID-19 have excessive blood clotting, which can be fatal.

A pilot study of hospitalized patients suggests that a low dose of the anticoagulant aspirin could reduce the need for mechanical ventilation and admission to intensive care, as well as the risk of dying.

A larger clinical study will be necessary to confirm the findings...

...(Jonathan Chow, M.D., assistant professor of anesthesiology and critical care medicine at the George Washington University School of Medicine and Health Sciences in Washington, D.C. and colleagues) analysis suggests that a low dose of aspirin shortly before or after hospital admission is associated with a significantly reduced risk of mechanical ventilation, admission to intensive care, and in-hospital mortality.

At the same time, the researchers found no evidence that aspirin increased the risk of bleeding.

...In addition to preventing clotting, aspirin reduces levels of an immune signaling molecule or cytokine called interleukin-6 (IL-6) in the blood. The molecule is associated with the immune overreaction, or “cytokine storm,” that can affect people with COVID-19 in intensive care.

https://www.medicalnewstoday.com/articles/aspirin-may-reduce-deaths-in-severe-co...

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Chow, Jonathan H. et al. 2021. Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019. Anesthesia & Analgesia: April 2021 - Volume 132 - Issue 4 - p 930-941 doi: 10.1213/ANE.0000000000005292 https://journals.lww.com/anesthesia-analgesia/Fulltext/2021/04000/Aspirin_Use_Is...

Abstract
BACKGROUND:
Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality.

METHODS:
A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions.

RESULTS:
Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin...) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, ...), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin...). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, ...7), ICU admission (adjusted HR, 0.57, ...), and in-hospital mortality (adjusted HR, 0.53...). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users.

CONCLUSIONS:
Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

...METHODS
...Aspirin Use Definition
Aspirin use was defined as administration within 24 hours of hospital admission or in the 7 days before hospital admission. This definition was selected based on aspirin’s prolonged duration of action as an irreversible platelet inhibitor and because of aspirin’s rapid onset within 0–4 hours when chewed or swallowed...

...RESULTS
Four hundred twelve patients were included in the study. Median age was 55 years ..., and 59.2% of patients were male ... Ninety-eight patients (23.7%) received aspirin, while 314 patients (76.3%) did not. Of those who received aspirin, 75.5% were taking it before admission and 86.7% received it within 24 hours of hospital admission. Median time to aspirin administration in the hospital was 0 days ..., median dose was 81 mg ..., and median treatment duration was 6 days.... Patients who received aspirin had significantly higher rates of hypertension, diabetes mellitus, coronary artery disease, and renal disease... Furthermore, significantly more patients taking aspirin were on home beta-blockers ... and had liver disease ... The proportion of patients in each group receiving other therapeutics, including azithromycin, convalescent plasma, dexamethasone, therapeutic heparin, hydroxychloroquine, remdesivir, and tocilizumab, did not differ...

>70 jjwilson61: JJwilson, I keep providing facts, and you keep throwing flounders into the conversation. Is this like O. J. Simpson's lawyers submitting someone had to have a degree in dog psychology to say that a dog was barking excitedly?
Great minds talk about concepts. Mediocre minds discuss procedures. Lesser minds just talk about people. My class in Electron Microscopy was under Dr. Misch, at the nation's oldest university. That doesn't make me smart, but it might allow my freedom of expression without your permission.

Some Covid-19 Patients Say They’re Left With Ringing Ears
Scientists are examining a possible link to tinnitus. A businessman’s suicide has lent urgency to the research.
David Segal | March 23, 2021

...A study published on Monday in the Journal of International Audiology that looked at nearly 60 case reports and studies found that 15 percent of adults with Covid-19 reported symptoms of tinnitus. The authors believe that the respondents were describing either a new condition or a worsening one, though they are following up with the 60 or so researchers to be certain about how the surveys were worded.

...There is also some evidence that Covid-19 can aggravate symptoms among people who had tinnitus before they contracted the disease. A study published late last year in the journal Frontiers in Public Health surveyed 3,100 people with tinnitus and found that 40 percent of the 237 respondents who had contracted Covid-19 reported that their symptoms were “significantly exacerbated” following the infection...

https://www.nytimes.com/2021/03/23/health/coronavirus-tinnitus.html
-------------------------------------------------------------

Ibrahim Almufarrij & Kevin J. Munro. 2021. One year on: an updated systematic review of SARS-CoV-2, COVID-19 and audio-vestibular symptoms. International Journal of Audiology (22 Mar 2021) https://doi.org/10.1080/14992027.2021.1896793 https://www.tandfonline.com/doi/full/10.1080/14992027.2021.1896793

Abstract
Objective
The aim was to systematically review the literature to December 2020, in order to provide a timely summary of evidence on SARS-CoV-2, COVID-19 and audio-vestibular symptoms.

Design...
Study sample...

Results
There are multiple reports of hearing loss (e.g. sudden sensorineural), tinnitus and rotatory vertigo in adults having a wide range of COVID-19 symptom severity. The pooled estimate of prevalence based primarily on retrospective recall of symptoms, was 7.6%..., 14.8%... and 7.2% ..., for hearing loss, tinnitus and rotatory vertigo, respectively. However, these could be an over-estimate because it was not always clear that studies report a change in symptom.

Conclusion
There are multiple reports of audio-vestibular symptoms associated with COVID-19. However, there is a dearth of high-quality studies comparing COVID-19 cases and controls.

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Eldré W. Beukes et al. 2020. Changes in Tinnitus Experiences During the COVID-19 Pandemic. Front. Public Health, 05 November 2020 | https://doi.org/10.3389/fpubh.2020.592878 https://www.frontiersin.org/articles/10.3389/fpubh.2020.592878/full

Introduction....

Methods: This is a mixed-methods exploratory cross-sectional study, using data collected via an online survey from 3,103 individuals with tinnitus from 48 countries. The greatest representation was from North America (49%) and Europe (47%) and other countries were only marginally represented.

Results: Although the study was aimed at those with pre-existing tinnitus, 7 individuals reported having COVID-19 initiated tinnitus. Having COVID-19 symptoms exacerbated tinnitus in 40% of respondents, made no change in 54%, and improved tinnitus in 6%. Other mediating factors such as the social and emotional consequences of the pandemic made pre-existing tinnitus more bothersome for 32% of the respondents, particularly for females and younger adults, better for 1%, and caused no change to tinnitus for 67%. Pre-existing tinnitus was significantly exacerbated for those self-isolating, experiencing loneliness, sleeping poorly, and with reduced levels of exercise. Increased depression, anxiety, irritability, and financial worries further significantly contributed to tinnitus being more bothersome during the pandemic period.

Conclusions: These findings have implications for tinnitus management, because they highlight the diverse response both internal and external factors have on tinnitus levels. Clinical services should be mindful that tinnitus may be caused by contracting COVID-19 and pre-existing tinnitus may be exacerbated, although in the majority of respondents there was no change. Additional support should be offered where tinnitus severity has increased due to the health, social, and/or emotional effects of the COVID-19 pandemic. Tinnitus may be more bothersome for those experiencing loneliness, having fewer social interactions, and who are more anxious or worried.

If Everything Smells Bad, You’re Not Alone
Parosmia, a condition that causes phantom odors and a lingering symptom of Covid-19 for some people, has been affecting relationships.
Alyson Krueger | March 22, 2021

... parosmia, a distortion of smell such that previously enjoyable aromas — like that of fresh coffee or a romantic partner — may become unpleasant and even intolerable. Along with anosmia, or diminished sense of smell, it is a symptom that has lingered with some people who have recovered from Covid-19.

...One recent review* found that 47 percent of people with Covid-19 had smell and taste changes; of those, about half reported developing parosmia.

...“It’s a much bigger issue than people give it credit for,” said Dr. Duika Burges Watson, who leads the Altered Eating Research Network at Newcastle University in England and submitted a journal research paper** on the topic. “It is something affecting your relationship with yourself, with others, your social life, your intimate relationships.”...

https://www.nytimes.com/2021/03/22/style/smell-covid-dating-parosmia.html

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* Claire Hopkins & Christine Kelly. 2021. Prevalence and persistence of smell and taste dysfunction in COVID-19; how should dental practices apply diagnostic criteria? BDJ In Practice volume 34, pages 22–23 (Feb 8, 2021) https://www.nature.com/articles/s41404-021-0652-4

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

** Duika L Burges Watson et al. 2020. Altered Smell and Taste: anosmia, parosmia and the impact of long Covid-19. MedRxiv (Nov 30, 2020) doi: https://doi.org/10.1101/2020.11.26.20239152 https://www.medrxiv.org/content/10.1101/2020.11.26.20239152v1.full

This article is a preprint and has not been peer-reviewed

>51 margd: >53 margd: AstraZeneca efficacy, take 3... Vaccine looks to be just fine. The company, however...

Pushing back against U.S. health officials, AstraZeneca says new analysis confirms efficacy of its Covid-19 vaccine
Matthew Herper | March 24, 2021

Rejecting sharp criticism from U.S. government scientists, AstraZeneca said Wednesday night that its Covid-19 vaccine was 76% effective at reducing the risk of symptomatic Covid-19, and 100% effective against severe disease, in a new analysis of its large U.S.-based clinical trial.

Those estimates were just a few percentage points lower than much more sparse results the company released Monday from an earlier analysis of the study, despite dramatic statements from government scientists that AstraZeneca’s initial release may have used “outdated information” that could have been overly favorable.

...Based on a statistical measure called confidence intervals given in the press release, the end result on overall efficacy could be anywhere between 68% and 82% — figures that would more than pass the Food and Drug Administration’s criteria for an emergency use authorization. AstraZeneca said it would file for such an authorization in the coming weeks.

All the results look more robust than data from an earlier pooled analysis of clinical trials in the U.K., South Africa, and Brazil, which showed a roughly 62% efficacy for the vaccine.

After all the twists and turns, though, several researchers reached by STAT said they would prefer to wait until more results are available before drawing firm conclusions. AstraZeneca has said it would publish the results in a peer-reviewed medical journal. In deciding whether to grant an authorization, the FDA will rely not on AstraZeneca’s estimates but on its own analysis of the raw data...

https://www.statnews.com/2021/03/24/pushing-back-against-u-s-health-officials-as...
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ZD1222 US Phase III primary analysis confirms safety and efficacy
AstraZeneca (Release) | 25 March 2021
25 March 2021

76% vaccine efficacy against symptomatic COVID-19
100% efficacy against severe or critical disease and hospitalisation
85% efficacy against symptomatic COVID-19 in participants aged 65 years and over...

https://www.astrazeneca.com/media-centre/press-releases/2021/azd1222-us-phase-ii...

Kevin D. McCormick et al. 2021. The emerging plasticity of SARS-CoV-2. Science 26 Mar 2021: Vol. 371, Issue 6536, pp. 1306-1308 DOI: 10.1126/science.abg4493 https://science.sciencemag.org/content/371/6536/1306


Viruses evolve as a result of mutation (misincorporations, insertions or deletions, and recombination) and natural selection for favorable traits such as more efficient viral replication, transmission, and evasion of host defenses...

Although SARS-CoV-2 shares high sequence homology with SARS-CoV, which caused the 2002–2004 SARS outbreak, the coronavirus family is diverse in both sequence and in host receptor preference....

The S protein comprises two subunits: S1, which contains the RBD, and S2, which mediates virus–host cell fusion...

Extensive intrahost evolution of SARS-CoV-2 has been reported in at least five individuals with protracted infection because of immune impairment from therapy for hematologic malignancies or autoimmunity...

These reports preceded the detection of three major circulating variants—B.1.1.7, B.1.351, and P.1—which all contain at least eight single, nonsynonymous nucleotide changes, including E484K, N501Y, and/or K417N (Lys417→Asn) in the ACE2 interface of the RBD...

Because only a few SARS-CoV-2 mutations were in circulation during most of 2020, it is likely that the three major variants are the result of selective pressures and adaptation of the virus during prolonged individual infections and subsequent transmission...

The individual phenotypic effects of the mutations in S1 are incompletely understood, but some initial clues are emerging...

It is possible that mutations that reduce neutralizing antibody binding, such as E484K, may require compensatory mutations that restore infectivity, such as N501Y...

It is not yet known whether the complex mutational patterns observed in SARS-CoV-2 variants are linked on the same viral genome or represent mixtures of different variants within the same patient...

Several studies suggest that the major circulating variants have reduced neutralizing sensitivity to CP and plasma from recently vaccinated individuals...

Phase 3 trials of SARS-CoV-2 vaccines derived from a single S sequence have shown them to be highly effective in preventing infection with the initial SARS-CoV-2 variants, including those with the D614G mutation...

The growing evidence for the emergence of immune escape mutations in protracted SARS-CoV-2 infection and for multiple, rapidly spreading variants should raise broad concern and action. Reducing the spread of SARS-CoV-2 is most likely to prevent further selection of immune escape variants. This will require a coordinated and comprehensive global vaccination and prevention strategy. Partial roll-out and incomplete immunization of individuals leading to suboptimal titers of neutralizing antibody could promote selection of escape variants that negatively affect vaccine efficacy. Increased genotypic and phenotypic testing capacities are essential worldwide to detect and characterize circulating SARS-CoV-2 variants that may emerge from selection by natural or vaccine-mediated immune responses. Infections that occur among vaccinated individuals should be aggressively evaluated for the mechanisms of breakthrough. The explosive, global spread of SARS-CoV-2 and the devastation it has wreaked is a stark warning of the potential for new variants to further complicate pandemic control. Vaccine manufacturers are now testing potential booster vaccines against circulating SARS-CoV-2 variants, and more broadly active monoclonal antibodies are in development for therapy. Such proactive approaches are likely to be needed to ensure pandemic control and elimination.

https://science.sciencemag.org/content/371/6536/1306

Yikes? Possible new variant in three Tanzanian travelers in Angola. It has "constellation of mutations with known or suspected biological significance, specifically resistance to neutralizing antibodies and potentially increased transmissibility."

Tulio de Oliveira (Mandela School of Medicine, U Washington) @Tuliodna | 12:05 PM · Mar 25, 2021:
For images:
https://twitter.com/Tuliodna/status/1375116665227247620
https://threadreaderapp.com/thread/1375116665227247620.html

We just submitted a pre-print 'A novel variant of interest (VOI) of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa.'
This VOI has 31 amino acids mutations. In Spike has 11 mutations and three deletions in the N-terminal domain...

It has some key mutations, including the E484K, R346K and P681H. The R346K is the associated with resistance to class 3 RBD NAbs recently described by @jbloom_lab
There are also 5 substitutions and 3 deletions in the NTD antigenic supersite (Y144Δ, R246M, SYL247-249Δ and W258L)

It the most diverse A lineage sequencers ever described. It also worry us as it was found in three travelers from Tanzania in Angola. There is almost no data from COVID-19 in Tanzania.

When compared with other variants of concern and variants of interest, this is the most divergent one.

Manuscript has been deposited at medRxiv and until online is freely accessible at: https://krisp.org.za/publications.php?pubid=330 *
Sequences are available in GISAID with accessions: EPI_ISL_1347940, EPI_ISL_1347941, EPI_ISL_1347942

We decided to report this as a new VOI given the constellation of mutations with known or suspected biological significance, specifically resistance to neutralizing antibodies and potentially increased transmissibility.

Whilst we have only detected three cases with this new VOI, this warrants urgent investigation as the source country, Tanzania, has a largely undocumented epidemic and few public health measures in place to prevent spread within and out of the country.

Thanks @AfricaCDC, Minister of Health of Angola, @rjlessells @houzhou @Mittenavoig and many other colleagues from Angola and Africa to help on the analysis of the data.
-----------------------------------------------------------

de Oliveira T et al. 2021. A novel variant of interest of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa. medRxiv,: (2021) https://www.krisp.org.za/publications.php?pubid=330

Abstract
At the end of 2020, the Network for Genomic Surveillance in South Africa (NGS-SA) detected a SARS-CoV-2 variant of concern (VOC) in South Africa (501Y.V2 or PANGO lineage B.1.351)... 501Y.V2 is associated with increased transmissibility and resistance to neutralizing antibodies elicited by natural infection and vaccination... 501Y.V2 has since spread to over 50 countries around the world and has contributed to a significant resurgence of the epidemic in southern Africa. In order to rapidly characterize the spread of this and other emerging VOCs and variants of interest (VOIs), NGS-SA partnered with the Africa Centres for Disease Control and Prevention and the African Society of Laboratory Medicine through the Africa Pathogen Genomics Initiative to strengthen SARS-CoV-2 genomic surveillance across the region.

Here, we report the first genomic surveillance results from Angola, which has had 21 500 reported cases and around 500 deaths from COVID-19 up to March 2021 (Supplemental Fig S1). On 15 January 2021, in response to the international spread of VOCs, the government instituted compulsory rapid antigen testing of all passengers arriving at the main international airport, in addition to the existing requirement to present a negative PCR test taken within 72 hours of travel. All individuals with a positive antigen test are isolated in a government facility for a minimum of 14 days and require two negative RT-PCR tests at least 48 hours apart for de-isolation, whilst all travelers with a negative test on arrival proceed to mandatory self-quarantine for 10 days followed by a repeat test. In March 2021, we received 118 nasopharyngeal swab samples collected between June 2020 and February 2021, a number of which were from incoming air travelers (Supplemental Fig S1). From these, we produced 73 high quality genomes (>80 margd:% coverage), 14 of which were known VOCs/VOIs (seven 501Y.V2/B.1.351, six B.1.1.7, one B.1.525), 44 of which were C.16 (a common lineage circulating in Portugal), and twelve of which were other lineages (Supplemental Fig S2). In addition, we detected a new VOI in three incoming travelers from Tanzania who were tested together at the airport in mid-February. The three genomes from these passengers were almost identical and presented highly divergent sequences within the A lineage (Figure 1A & 1B). The GISAID database contains nine other sequences reported to be sampled from cases involving travel from Tanzania, two of which are basal to the three sampled in Angola

This new VOI, temporarily designated A.VOI.V2, has 31 amino acid substitutions (11 in spike) and three deletions (all in spike) (Figure 1C & 1D). The spike mutations include three substitutions in the receptor-binding domain (R346K, T478R and E484K); five substitutions and three deletions in the N-terminal domain, some of which are within the antigenic supersite (Y144?, R246M, SYL247-249? and W258L)4; and two substitutions adjacent to the S1/S2 cleavage site (H655Y and P681H). Several of these mutations are present in other VOCs/VOIs and are evolving under positive selection.

Good news for previously infected: A single mRNA immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold.

Eric Topol: "Besides cross-reacting antibodies, this report provides further support for only 1 dose of vaccine needed for people with prior covid..."

Leonidas Stamatatos et al. 2021. mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.
Science 25 Mar 2021:eabg9175 DOI: 10.1126/science.abg9175 https://science.sciencemag.org/content/early/2021/03/24/science.abg9175.abstract

Abstract
Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naïve donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.

Tech Tips to Help Score a Covid-19 Vaccine Appointment at CVS, Rite Aid, Walgreens and More
Setting up alerts and browser tools helped our columnist schedule time slots for eligible friends and family members in a variety of states
Joanna Stern | March 1, 2021

https://www.wsj.com/articles/tech-tips-to-help-score-a-covid-19-vaccine-appointm...

:( Poor Brazil appears to be in hands of its own Scott Atlas, or worse:
"a Lockdown will not work because fleas, mosquitoes and ants could carry the virus"

Luis F.B.Correia M.D (Radio CBN) @SaudeemFoco | 9:43 PM · Mar 25, 2021:
#COVID Brazilian Minister - Onyx Lorenzoni says in radio broadcast that a Lockdown will not work because fleas, mosquitoes and ants could carry the virus. Now anyone can understand why Brazil is that terrible condition.

Onyx, ministro de Bolsonaro, diz que lockdown não funcionaria porque formigas e pulgas poderiam...
Afirmações do bolsonarista, entretanto, não encontram qualquer respaldo científico; especialistas apontam a urgência do lockdown

https://www.cartacapital.com.br/cartaexpressa/onyx-ministro-de-bolsonaro-diz-que...

__________________________________________________

Eric Feigl-Ding @DrEricDing | 10:32 PM · Mar 25, 2021:
Brazil #P1 now invading neighbors:
Paraguay Minister of Health “confirms that the Manaus, Brazil variant is already circulating in the country".
ICUs in Paraguay are now maxed out—#COVID19 deaths surging...

1:05 ( https://twitter.com/DrEricDing/status/1375274363843444742 )
From Paraguay TV

Eric Topol (Scripps physician-scientist) @EricTopol | 10:55 AM · Mar 26, 2021:
It's not over or under control until all boats float.
Europe on the rise, new case records today in Poland, Hungary, Ukraine
South America (especially Brazil, Chile) and Southeast Asia (India) are on the ascent

Image ( https://twitter.com/EricTopol/status/1375461475716800513/photo/1 )

Pregnant women show robust immune response to COVID vaccines, pass antibodies to newborns
Massachusetts General Hospital | March 25, 2021

Summary:
Researchers have found the new mRNA COVID-19 vaccines to be highly effective in producing antibodies against the SARS-CoV-2 virus in pregnant and lactating women. They also demonstrated the vaccines confer protective immunity to newborns through breastmilk and the placenta....

https://www.sciencedaily.com/releases/2021/03/210325150127.htm
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Kathryn J. Gray, Evan A. Bordt, Caroline Atyeo, Elizabeth Deriso, Babatunde Akinwunmi, Nicola Young, Aranxta Medina Baez, Lydia L. Shook, Dana Cvrk, Kaitlyn James, Rose De Guzman, Sara Brigida, Khady Diouf, Ilona Goldfarb, Lisa M. Bebell, Lael M. Yonker, Alessio Fasano, S. Alireza Rabi, Michal A. Elovitz, Galit Alter, Andrea G. Edlow. COVID-19 vaccine response in pregnant and lactating women: a cohort study. American Journal of Obstetrics and Gynecology, March 25, 2021; DOI: 10.1016/j.ajog.2021.03.023 https://www.ajog.org/article/S0002-9378(21)00187-3/pdf (Journal pre-proof)

CONDENSATION: COVID-19 vaccination confers a robust humoral response in pregnant and lactating women and immune transfer to neonates newborns via placenta and breastmilk....

B. What are the key findings? Pregnant and lactating women elicited comparable vaccine-induced humoral immune responses to non-pregnant controls, and generated higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy. Vaccine-generated antibodies were present in umbilical cord blood and breastmilk after maternal vaccination...

ABSTRACT
Background: Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.

Objectives: To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.

Study Design: 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-94 pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM (three kinds of immunoglobulin) were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.

Results: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median ... 5.59... pregnant, 5.74 ...lactating, 5.62... non-pregnant...). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy.... Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median ... 104.7... maternal sera, 52.3 ... cord 111 sera...). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity ( common, "expected" adverse reactions, including fever, sore arm at the injection site) across the groups.

Conclusions: COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk...

INTRODUCTION...

MATERIALS AND METHODS
Study Design...
Participants and Procedures...
Sample Collection and Processing...
Antibody Quantification...
Antibody Neutralization Assay...
Statistical Analyses...

RESULTS
Participant characteristics...
Vaccination characteristics...
Delivery outcomes and characteristics of lactating women...
The maternal vaccine response...
Impact of maternal vaccination on breastmilk antibody transfer...
Impact of maternal vaccination on placental antibody transfer...
Vaccine reactogenicity in pregnancy and lactation ...

DISCUSSION
Principal Findings...
Results...

Clinical Implications
When considering vaccination in pregnancy, evidence regarding maternal and fetal benefit, as well as potential maternal and fetal harm and effects on pregnancy outcomes should be weighed carefully. While the absolute risk of severe COVID-19 is low in pregnant women, pregnancy is a risk factor for severe disease. There are well-documented maternal, neonatal, and obstetric risks of SARS-CoV-2 infection during pregnancy. These data provide a compelling argument that COVID-19 mRNA vaccines induce similar humoral immunity in pregnant and lactating women as in the non-pregnant population. These data do not elucidate potential risks to the fetus.

Research Implications ...

Strengths and Limitations...
Conclusions

6,000 students + 12,500 close contacts + 20 universities (= 20 communities) unnecessarily put to risk in era of B117?
Isn't there a safer approach to determine post-vax transmission?

NIAID Launches Trial to Assess Post-Vax COVID Transmission Risk
— Fauci: Results to guide "science-based decisions" on masks, social distancing
Shannon Firth | March 26, 2021

...The open-label randomized trial, which began on Thursday, will test whether vaccine prevents both infection and transmission of SARS-CoV-2 among college students, and will "help inform science-based decisions about mask use and about social distancing post-vaccination," Fauci added.

The NIH-funded study will include 12,000 college students ages 18 to 26 from more than 20 universities, and is expected to last 5 months, Fauci said. One group of 6,000 students will receive their first dose of the Moderna vaccine immediately. The others will serve as controls and will receive their vaccine 4 months later.

All participants will ultimately receive the usual two doses.

Participants will swab their noses daily for SARS-CoV-2 infection, provide blood samples periodically, and complete surveys through an electronic diary app. They will also be asked to follow their university's SARS-CoV-2 protocols and get tested twice each week, according to the study's website.

Anyone who tests positive will be asked to follow additional protocols.

Another 25,000 individuals whom participants name as "close contacts" -- for example, roommates or co-workers -- will also provide blood samples to the researchers, take daily nose swabs for 2 weeks, and answer weekly questionnaires (if they agree to participate, of course).

"The degree of transmission from vaccinated individuals will be determined by the infection rate in the close contacts," Fauci explained...

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/91832

Whoa, (Dr?) Andersen, lead author of a study published in Nature Medicine last year which found that the virus was a product of natural evolution, tell us how you really feel!

"No evidence" to support former CDC director's (Redfield) theory that coronavirus escaped from lab, scientists say
Audrey McNamara | March 27, 2021

Kristian G. Andersen, director of the infectious disease genomics, translational research institute at Scripps Research:
"It is clear that not only was (Redfield) the most disastrous CDC director in U.S. history where he utterly failed in his sworn mission to keep the country safe, but via his comments, he also shows a complete lack of basic evolutionary virology"

https://www.cbsnews.com/news/covid-lab-theory-robert-redfield-no-evidence/

For Biden, a New Virus Dilemma: How to Handle a Looming Glut of Vaccine
As U.S. manufacturers hit their stride, vaccine scarcity will soon turn to plenty as much of the world goes begging. And vaccine makers need answers now about what to do with the coming surplus.
Sharon LaFraniere and Noah Weiland | March 26, 2021

Federal health officials have also discussed canceling or reducing some orders from Moderna and Pfizer in return for the promise of a fresh supply this fall of either pediatric doses or shots of a new vaccine that has been reconfigured to work against the fast-spreading variants.

There is some push for that from the manufacturers, whose vaccines are coveted by other high-income countries. But it would also deprive federal officials of the power to decide which nations get the surplus doses, as well as the humanitarian and diplomatic credit it would reap from sending the vaccine to countries in greater need.

For all these reasons, senior officials say, the administration is leaning toward keeping the doses it has ordered then at some point directing the excess to other nations in bilateral deals or giving it to Covax, an international nonprofit organization backed by the World Health Organization that is trying to coordinate equitable distribution of vaccine. The Biden administration has already donated $4 billion to that international effort.

...the supply would be enough to vaccinate 650 million people — nearly twice the U.S. population...

https://www.nytimes.com/2021/03/26/us/biden-coronavirus-vaccine.html

Mexico’s real COVID-19 death toll now stands at over 321,000
AP | 3/28/2021

Mexico’s government acknowledged Saturday that the country’s true death toll from the coronavirus pandemic now stands above 321,000, almost 60% more than the official test-confirmed number of 201,429.

Mexico does little testing, and because hospitals were overwhelmed, many Mexicans died at home without getting a test. The only way to get a clear picture is to review “excess deaths” and review death certificates.

...The higher toll would rival that of Brazil, which currently has the world’s second-highest number of deaths after the United States. But Mexico’s population of 126 million is far smaller than either of those countries.

...Also suggestive were the overall number of “excess deaths” since the pandemic began, around 417,000. Excess deaths are determined by comparing the deaths in a given year to those that would be expected based on data from previous years...

https://apnews.com/article/coronavirus-pandemic-latin-america-mexico-c0577354d8b...

Kenya HealthCare Professionals @HealthProfKE | 2:40 AM · Mar 26, 2021
Media Invite 10.00 AM (Friday? March 28?)
On COVID 19 Vaccine roll out

Image ( https://twitter.com/HealthProfKE/status/1375336767629504515/photo/1 )
Nation Breaking News and 7 others

>19 margd: Should you get the vaccine? Yes. Will it help Long COVID? This says, statistically, we see some positive effect; we don't know how long the effect lasts. Is it placebo? It really shouldn't matter to anyone getting the shot; the effect is the same either way.

Percentage of population who have had their first dose of the #COVID19 vaccine (top 50 countries):

Image ( https://twitter.com/DrJacobsRad/status/1376022111291068419/photo/1 )
Image ( https://twitter.com/DrJacobsRad/status/1376022111291068419/photo/2 )
Image ( https://twitter.com/DrJacobsRad/status/1376022111291068419/photo/3 )
Image ( https://twitter.com/DrJacobsRad/status/1376022111291068419/photo/4 )

- David Jacobs @DrJacobsRad | 12:03 AM · Mar 28, 2021

Image--graph of COVID cases per 100 million by continent, march 1, 202 - March 27, 2021:
https://twitter.com/EricTopol/status/1376181289104011269/photo/1

How The Coronavirus Vaccines Affect Long-Haul COVID-19 Patients
March 28, 20217:56 AM ET
Heard on Weekend Edition Sunday: 4-Minute Listen

NPR's Sarah McCammon speaks to Immunologist Akiko Iwasaki discusses the effects of the vaccine on long-haul COVID-19 patients.

https://www.npr.org/2021/03/28/982034977/how-the-coronavirus-vaccines-affect-lon...

The Data Visualizations Behind COVID-19 Skepticism

Research By Crystal Lee, Tanya Yang, Gabrielle Inchoco, Graham M. Jones, and Arvind Satyanarayan
Interactive Article By Crystal Lee, Jonathan Zong, Anna Arpaci-Dusseau, Katherine Huang, Mateo Monterde, Ethan Nevidomsky, Tanya Yang, Anna Meurer, Soomin Chun, and Arvind Satyanarayan
March 1, 2021

How do COVID-19 skeptics use public health data and social media to advocate for reopening the economy and against mask mandates?

We studied half a million tweets, over 41,000 visualizations, and spent six months lurking in anti-mask Facebook groups.

Here’s what we found...

http://vis.mit.edu/covid-story/

A rare clotting disorder may cloud the world's hopes for AstraZeneca's COVID-19 vaccine
Kai Kupferschmidt, Gretchen Vogel (Science Magazine)| Mar. 27, 2021

...a group of researchers led by German clotting specialist Andreas Greinacher of the University of Greifswald says the highly unusual combination of symptoms—widespread blood clots and a low platelet count, sometimes with bleeding—resembles a rare side effect of the blood thinner heparin called heparin-induced thrombocytopenia (HIT).

...Greinacher, who calls the syndrome vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)...says he has submitted a manuscript to the preprint server Research Square.

...Greinacher...says it's crucial to alert doctors to the potential complication. When recognized in time, HIT can be treated with immunoglobulins—nonspecific antibodies from blood donors—that help put the brakes on platelet activation. Nonheparin blood thinners can help dissolve the clots. VIPIT should be treated in a similar way, he says. In at least one case, Greinacher says, a doctor sought the group’s advice and the patient recovered.

...The German Society for the Study of Thrombosis and Hemostasis, of which Greinacher is a member, has issued a set of recommendations for diagnosing and treating VIPIT.*

...Monday meeting of (European Medicines Agency) EMA's expert group, which includes clotting experts, neurologists, virologists, immunologists, and epidemiologists. The agency (EMA) says it will issue an update on the vaccine during the next meeting of its safety committee, being held from 6-9 April. Ideally, that meeting will help clarify how frequently the condition occurs and whether the risk varies by age or sex, (Saskia Middeldorp, a vascular internist at Radboud University Medical Center in the Netherlands, who disagreed with the temporary halt of the vaccine because she says the benefits clearly outweigh the risks) says. The world needs AstraZeneca's vaccine, she says—but that means it is crucial to fully understand its benefits and its risks.

https://www.sciencemag.org/news/2021/03/rare-clotting-disorder-may-cloud-worlds-...
doi:10.1126/science.abi7283

-------------------------------------------------------------
The German Society for the Study of Thrombosis and Hemostasis, of which Greinacher is a member, has issued a set of recommendations for diagnosing and treating VIPIT:

* Updated GTH statement on vaccination with the AstraZeneca COVID-19 vaccine, as of March 22, 2021
GTH Geschäftsstelle –Gertrudenstr. 9-50667Köln/ GermanyCologne, 03/22/2021
4 p
https://gth-online.org/wp-content/uploads/2021/03/GTH_Stellungnahme_AstraZeneca_...

Karibu, Kamaal.

>95 Kamaal22: Can people who were vaccinated get COV19?

Yes.

For example, the risk of acquiring the disease for an INDIVIDUAL Pfizer vaccinee is reduced 95%, so 1 in 20 chance.
(The risk of individual vaccinee dying or developing severe disease requiring hospitalization is pretty much zero.)

With the disease risk for an individual so low, the risk drops to zero once a sufficient number in the POPULATION are vaccinated, i.e., herd immunity.

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

Eric Topol (Scripps physician scientist) @EricTopol | 9:54 PM · Mar 26, 2021
CDC graph @maddow shows the marked survival benefit of vaccines
when more than 71% of age ≥ 65 have received ≥ 1 dose (and 46% fully vaccinated)

COVID-19 Weekly Cases and Deaths per 100,000 Population, U.S., by Age Group, March 1, 2020-March 25, 2021. (GRAPH)
https://twitter.com/EricTopol/status/1375627364269391872/photo/1

Eric Topol @EricTopol | 10:01 AM · Mar 29, 2021
New @NatureMedicine: The concern about asymptomatic transmission addressed in nearly 5,000 people after 1st dose of mRNA vaccine (~2 -5 wks). Viral load markedly reduced (high Ct). Supports vaccine effect for blocking or strongly reducing chance of spread
Image ( https://twitter.com/EricTopol/status/1376535017287938055/photo/1 )
Image ( https://twitter.com/EricTopol/status/1376535017287938055/photo/2 )
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Levine-Tiefenbrun, M., Yelin, I., Katz, R. et al. Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 (Pfizer BioNTech) vaccine. Nat Med (2021). https://doi.org/10.1038/s41591-021-01316-7 https://www.nature.com/articles/s41591-021-01316-7

Abstract
Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12–37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread...

"a first infection with SARS-CoV-2 provides only 47% protection against a second infection for those aged 65 years and over, compared with 80% protection across all age groups"

Limited protection against SARS-CoV-2 reinfection in over 65s
A new study investigates reinfection with SARS-CoV-2.
James Kingsland | March 29, 2021

Research suggests that a first infection with SARS-CoV-2 provides only 47% protection against a second infection for those aged 65 years and over, compared with 80% protection across all age groups.

These findings underscore the importance of physical distancing and vaccinations, even among those who have already had COVID-19.

The study found that the level of protection against reinfection remained stable for more than 6 months.

However, it did not take into account new variants of the virus, infection with which may provide less immunity against reinfection...

https://www.medicalnewstoday.com/articles/limited-protection-against-sars-cov-2-...

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Christian Holm Hansen et al. 2021. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. The Lancet Volume 397, ISSUE 10280, P1204-1212, March 27, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00575-4 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00575-4/fullt...

Summary
Background
The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2.

Methods
In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR.

Findings
During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65%...) tested positive again during the second surge compared with 16 819 (3·27%...) of 514 271 who tested negative during the first surge (adjusted RR 0·195 ...). Protection against repeat infection was 80·5% ... The alternative cohort analysis gave similar estimates (adjusted RR 0·212 ..., estimated protection 78·8%...). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% ...). We found no difference in estimated protection against repeat infection by sex (male 78·4%... vs female 79·1% ...) or evidence of waning protection over time (3–6 months of follow-up 79·3%... vs 7 months or more of follow-up 77·7% ...).

Interpretation
Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

ETA: https://nymag.com/intelligencer/2021/03/cdc-data-suggests-vaccinated-dont-carry-...

>97 margd: contd. YAY! So maybe I'm not a threat to my pregnant daughter-in-law! (I was more concerned than she was...)

‘Real world’ study by CDC shows Pfizer and Moderna vaccines were 90% effective (in preventing infections as well as disease)
Helen Branswell | March 29, 2021

A new study suggests the messenger RNA vaccines produced by Moderna and the Pfizer-BioNTech partnership appeared to be 90% effective in preventing Covid-19 infection in a real-world setting.

The study was released Monday in Morbidity and Mortality Weekly Report, an online journal published by the Centers for Disease Control and Prevention...

https://www.statnews.com/2021/03/29/real-world-study-by-cdc-shows-pfizer-and-mod...

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Thompson MG, Burgess JL, Naleway AL, et al. Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7013e3 https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e3.htm?s_cid=mm7013e3_w

Summary
What is already known about this topic?
Messenger RNA (mRNA) COVID-19 vaccines have been shown to be effective in preventing symptomatic SARS-CoV-2 infection in randomized placebo-controlled Phase III trials.

What is added by this report?
Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (14 days or more after first dose but before second dose) was 80%.

What are the implications for public health practice?
Authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

>93 margd: Here is preprint on clotting associated with nine Astrazeneca vaccinees (female, age 22-49, four of whom died) :

Andreas Greinacher et al. 2021. A Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced Thrombocytopenia Following Coronavirus-19 Vaccination. Research Square (March 29, 2021) DOI:10.21203/rs.3.rs-362354/v1 https://www.researchsquare.com/article/rs-362354/v1

EDITORIAL NOTE:
This study summarizes the clinical and laboratory features of 9 patients who exhibited blood clotting events following vaccination with AstraZeneca’s COVID-19 vaccine (AZD1222). The researchers suggest that these events resemble a known disorder – heparin-induced thrombocytopenia (HIT) – which is treatable if identified promptly. At the time of this posting, the World Health Organization maintains that the benefits of the AstraZeneca vaccine outweigh its risks and recommends that vaccinations continue. The authors disclose conflicts of interest, including personal fees from Pfizer and other pharmaceutical companies.

ABSTRACT
Background.
Vaccines are important for managing the COVID-19 pandemic caused by SARS-CoV-2. However, following widespread vaccination using a recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 (AZD1222, AstraZeneca), reports have emerged of some vaccine recipients developing unusual thrombotic events and thrombocytopenia. We investigated whether such patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against platelet factor 4 (PF4), as is known to be caused by heparin and sometimes other environmental triggers.

Methods.
We summarized the clinical and laboratory features of 9 patients in Germany and Austria who developed thrombosis and thrombocytopenia events following AZD1222 vaccination. Serum from four patients was used to test for anti-PF4/heparin antibodies, both by immunoassay and by platelet activation assays performed in the presence of heparin, PF4, or both.

Results.
The 9 patients (8 female; median age, 36 (range, 22—49) presented with thrombosis beginning 4 to 16 days post-vaccination: 7 patients had cerebral venous thrombosis (CVT), 1 had pulmonary embolism, and 1 had splanchnic vein thrombosis and CVT; 4 patients died. None had received heparin prior to symptom onset. All four patients tested strongly positive for anti-PF4/heparin antibodies by immunoassay; all 4 patients tested strongly positive in the platelet activation assay in the presence of PF4 independently of heparin. Platelet activation was inhibited by high concentrations of heparin, Fc receptor-blocking monoclonal antibody, and intravenous immunoglobulin.

Conclusions.
The AZD1222 vaccine is associated with development of a prothrombotic disorder that clinically resembles heparin-induced thrombocytopenia but which shows a different serological profile.

...DISCUSSION
...There are several important clinical implications of our findings.
(1) First, clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5 to 14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination. To date, this has only been reported with the AZD1222 vaccine.
(2) Second, enzyme-immunoassays for heparin-induced thrombocytopenia are widely available and based on our observations can be used to investigate for potential post-vaccination anti-PF4 antibody associated thrombocytopenia/thrombosis, especially as a strong-positive immunoassay result obtained in a patient who has not been recently exposed to heparin would be a striking abnormality. However, a positive PF4/heparin antigen test by no means confirms the presence of potentially pathogenic vaccine-induced antibodies, especially if the assay is moderate or weak positive, and thus referral to a laboratory that performs platelet-activation assays should be performed. Without clear clinical symptoms of new thrombosis and/or thrombocytopenia patients should not be tested or treated.
(3) Third, although this syndrome differs from typical heparin-induced thrombocytopenia, at least one patient showed strong platelet activation in the presence of heparin. In the absence of data indicating safety and efficacy of heparin in treating these patients, we would recommend therapy with non-heparin anticoagulants, such as those direct oral anticoagulants (rivaroxaban, apixaban) which are licensed without requirement for initial heparin therapy. Indeed, direct oral anticoagulants are widely used for treatment of thrombosis in general and have also been recommended for treatment of heparin-induced thrombocytopenia. And
(4) fourth, our in vitro studies of inhibition of the platelet-activating properties by high-dose immunoglobulin, together with the recent observations indicating efficacy of high-dose intravenous immunoglobulin for treating severe heparin-induced thrombocytopenia—including so-called “autoimmune heparin-induced thrombocytopenia” in which patients have de novo or ongoing thrombocytopenia in the absence of heparin—suggests that this can be an important treatment adjunct in a patient who develops life-threatening thrombotic event such as cerebral vein sinus thrombosis post-vaccination....
(5) Finally we suggest to name this entity vaccine induced prothrombotic immune thrombocytopenia (VIPIT) to avoid confusion with heparin-induced thrombocytopenia (HIT).

Why indoor spaces are still prime COVID hotspots
Risks shoot up when virus particles accumulate in buildings, but it’s not clear how best to improve ventilation.
Dyani Lewis | 30 March 2021

Slow recognition
Indoor threat
No set standards
Clearing the air

Nature 592, 22-25 (2021)
doi: https://doi.org/10.1038/d41586-021-00810-9
https://www.nature.com/articles/d41586-021-00810-9

Good discussion w both sides of (mRNA) COVID vaxx while pregnant question:

The evidence that Covid-19 vaccines are safe and effective in pregnancy is growing
Covid-19 shots during pregnancy might also pass on protection against the virus to babies.
Katherine Harmon Courage | Mar 30, 2021

...4 reasons the coronavirus vaccine should be okay to get while pregnant — but why not everyone is recommending it yet

One of the big reasons why, despite Covid-19’s known risks in pregnancy, not everyone has unequivocally recommended the vaccines that currently have emergency approval in the US for pregnant people is that the way they work is fairly new. But we do have some key pieces of information already:

1) These vaccines don’t contain live coronavirus...

2) The main coronavirus vaccines are very fragile. Once the mRNA enters the body, it likely only reaches local arm muscle cells before the body breaks it down...

3) Animal studies look promising.

4) We haven’t seen adverse events in pregnant people who have gotten it so far...a handful of people (12 who got the vaccine in Pfizer/BioNTech’s study and six who got the vaccine in Moderna’s study) ended up having been pregnant at the time of vaccination — and companies haven’t reported any negative outcomes from these individuals.

...At the beginning of March, the CDC reported data from more than 1,800 pregnant people in the registry who had received Covid-19 vaccines. Among these individuals, there was not a statistically significant increase in adverse pregnancy or birth outcomes. Nor have they found any significant differences in side effects from the vaccine (such as fatigue or fever)...

A January study published in JAMA Internal Medicine, for example, analyzed the outcomes of more than 406,000 people who gave birth in hospitals between April and November 2020 and found that a significantly higher rate of those with Covid-19 had major complications. “The higher rates of preterm birth, preeclampsia, thrombotic blood clotting events, and death in women giving birth with Covid-19 highlight the need for strategies to minimize risk,” noted the authors.

So why are some, such as the WHO and the UK, still saying most pregnant people should not get the coronavirus vaccine yet? They are waiting for more data...

https://www.vox.com/22348766/covid-19-vaccines-pregnancy-safe-effective-newborns...

The Pfizer-BioNTech Vaccine Is Said to Be Powerfully Protective in Adolescents
Apoorva Mandavilli | March 31, 2021

The Pfizer-BioNTech coronavirus vaccine is extremely effective in adolescents 12 to 15 years old, perhaps even more so than in adults, the companies reported on Wednesday. No infections were found among children who received the vaccine in a recent clinical trial, the drug makers said; the children produced strong antibody responses and experienced no serious side effects.

The findings, if they hold up, may speed a return to normalcy for millions of American families. Depending on regulatory approval, vaccinations could begin before the start of the next academic year for middle school and high school students, and for elementary school children not long after.

The companies announced the results in a news release that did not include detailed data from the trial, which has not yet been peer-reviewed nor published in a scientific journal. Still, the news drew praise and excitement from experts.

...The trial included 2,260 adolescents ages 12 to 15. The children received two doses of the vaccine three weeks apart — the same amounts and schedule used for adults — or a placebo of saltwater.

The researchers recorded 18 cases of coronavirus infection in the placebo group, and none among the children who received the vaccine....

The adolescents who got the vaccine produced much higher levels of antibodies on average, compared with participants 16 to 25 years of age in an earlier trial. The children experienced the same minor side effects as older participants, although the companies declined to be more specific.

https://www.nytimes.com/2021/03/31/health/pfizer-biontech-vaccine-adolescents.ht...

Florida COVID numbers face new scrutiny
Alexander Nazaryan | March 30, 2021

...New research published earlier this month in the American Journal of Public Health argues that Florida is undercounting the number of people who died from COVID-19 by thousands of cases, casting new doubt on claims that Gov. Ron DeSantis navigated the coronavirus pandemic successfully...

...In the case of Florida, the researchers say, 4,924 excess deaths should have been counted as resulting from COVID-19 but for the most part were ruled as having been caused by something else, thus lowering Florida’s coronavirus fatality count. That’s possible because people who die from COVID-19 often have comorbidities, such as diabetes and asthma. That leaves some discretion for medical examiners, who have sometimes struggled with conflicting science and been subject to political pressures during the pandemic.

In Florida, the state’s 25 district medical examiners are directly appointed by the governor. Last spring, the DeSantis administration was accused of trying to keep those medical examiners from releasing complete coronavirus data. (In August, the state said coronavirus deaths no longer required certification from a medical examiner.)

...Florida already has the fourth-highest total number of deaths in the country from COVID-19, but it is also the country’s second most populous state. It has the second-oldest population in the United States...

...Research conducted by Andrew Stokes of Boston University has shown that in pro-Trump sections of the country where elected officials tended to take the pandemic less seriously, excess deaths were less likely to be attributed to the coronavirus.

https://news.yahoo.com/florida-covid-numbers-face-new-scrutiny-090058319.html
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Moosa Tatar, Amir Habibdoust, Fernando A. Wilson, “Analysis of Excess Deaths During the COVID-19 Pandemic in the State of Florida”, American Journal of Public Health 111, no. 4 (April 1, 2021): pp. 704-707. https://doi.org/10.2105/AJPH.2020.306130 . https://ajph.aphapublications.org/doi/10.2105/AJPH.2020.306130

Objectives. To determine the number of excess deaths (i.e., those exceeding historical trends after accounting for COVID-19 deaths) occurring in Florida during the COVID-19 pandemic.

Methods. Using seasonal autoregressive integrated moving average time-series modeling and historical mortality trends in Florida, we forecasted monthly deaths from January to September of 2020 in the absence of the pandemic. We compared estimated deaths with monthly recorded total deaths (i.e., all deaths regardless of cause) during the COVID-19 pandemic and deaths only from COVID-19 to measure excess deaths in Florida.

Results. Our results suggest that Florida experienced 19 241 (15.5%) excess deaths above historical trends from March to September 2020, including 14 317 COVID-19 deaths and an additional 4924 all-cause, excluding COVID-19, deaths in that period.

Conclusions. Total deaths are significantly higher than historical trends in Florida even when accounting for COVID-19–related deaths. The impact of COVID-19 on mortality is significantly greater than the official COVID-19 data suggest.

Despite Chile’s Speedy Covid-19 Vaccination Drive, Cases Soar
Experts say Chile’s government eased restrictions on travel, business and schools much too early, creating a false sense of confidence that the worst of the pandemic was over.
Pascale Bonnefoy and Ernesto Londoño | March 30, 2021. Updated March 31, 2021

...experts say the country’s speedy and efficient vaccination drive — only Israel, the United Arab Emirates and Seychelles have vaccinated a larger share of their populations — gave Chileans a false sense of security and contributed to a sharp spike in new infections and deaths that is overloading the health care system.

The surge in cases, even as more than one-third of Chile’s population has received at least the first dose of a Covid-19 vaccine, serves as a cautionary tale for other nations looking to vaccination drives to quickly put an end to the era of beleaguered economies, closed borders and social distancing. The rise in cases prompted a new set of strict lockdown measures that have restricted mobility for much of the country, affecting nearly 14 million people...

https://www.nytimes.com/2021/03/30/world/americas/chile-vaccination-cases-surge....

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

...Chile is using SinoVac’s CoronaVac, which in Brazil only recorded 50.4% efficacy for total symptomatic infections. (It’s 78% effective in preventing mild cases that needed treatment and 100% effective for moderate to serious cases)
- https://twitter.com/DrEricDing/status/1377038778083258369

How Black faith leaders help their communities get vaccinated
Although COVID-19 is most harshly affecting Black communities in the United States, vaccination rates in these communities remain very low.
Robby Berman | March 30, 2021

A paper*proposes that a coalition of Black faith leaders, public health officials, and Black medical professionals may be able to increase the number of people getting vaccinated.

A test of the proposed model in southern California’s San Bernardino Valley resulted in a measurable increase in the rate of vaccinations.

As vaccines become more readily available in the U.S., attention has turned to the task of getting as many people vaccinated as possible...

https://www.medicalnewstoday.com/articles/how-black-faith-leaders-help-their-com...
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Jacinda C Abdul-Mutakabbir et al. 2021. A three-tiered approach to address barriers to COVID-19 vaccine delivery in the Black community. The Lancet Global Health ( Open Access. Published:March 10, 2021) DOI:https://doi.org/10.1016/S2214-109X(21)00099-1 https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00099-1/fullt...

...In conclusion, the equitable allocation of the COVID-19 vaccines is essential to confronting the racial disparities magnified by the current pandemic. Strategies to reach the Black community include:
(1) engagement of Black faith leaders;
(2) promotion of vaccine education by Black health-care professionals; and
(3) increasing accessibility of vaccination clinics by holding them in Black communities, so that online registration and scheduling are avoided.

A common cold virus may help fight COVID-19
James Kingsland | March 29, 2021

A lab-based study has found that a virus that causes the common cold can trigger an innate immune response against SARS-CoV-2, the virus responsible for COVID-19.

In theory, infections with the common cold virus could inhibit the transmission of SARS-CoV-2 among members of a population and reduce the severity of infections.

Further research could lead to control strategies or treatments that exploit such interactions between viruses...

https://www.medicalnewstoday.com/articles/a-common-cold-virus-may-help-fight-cov...

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Kieran Dee et al. 2021. Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology. The Journal of Infectious Diseases, jiab147, (23 March 2021) https://doi.org/10.1093/infdis/jiab147 https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab147/6179975

Abstract
Virus-virus interactions influence the epidemiology of respiratory infections. However, the impact of viruses causing upper respiratory infections on SARS-CoV-2 replication and transmission is currently unknown. Human rhinoviruses cause the common cold and are the most prevalent respiratory viruses of humans. Interactions between rhinoviruses and co-circulating respiratory viruses have been shown to shape virus epidemiology at the individual host and population level. Here, we examined the replication kinetics of SARS-CoV-2 in the human respiratory epithelium in the presence or absence of rhinovirus. We show that human rhinovirus triggers an interferon response that blocks SARS-CoV-2 replication. Mathematical simulations show that this virus-virus interaction is likely to have a population-wide effect as an increasing prevalence of rhinovirus will reduce the number of new COVID-19 cases.

Eric Topol @EricTopol | 4:53 PM · Mar 31, 2021:

Update on the 3 major variants
—Proven higher lethality of B.1.1.7
—More spread globally and US for all
—Vaccines work fine vs B.1.1.7,
some dropoff but preserved efficacy vs. B.1.351, and
unclear vs. P.1 but very encouraging ex vivo data (it has less immune evasion than B.1.351)

Image - table ( https://twitter.com/EricTopol/status/1377363376305664002/photo/1 )

Yikes, even with longterm care residents mostly vaxxed, Ontario's hospitals have a record number of COVID-19 patients in ICUs... Not an April Fool's Day joke, Ontario enters monthlong lockdown April 3, 2021:

Ford government hitting 'emergency brake' to put all Ontario in lockdown: sources
CBC News | Mar 31, 2021

Ontario Premier Doug Ford's government will announce on Thursday that it's putting the entire province under lockdown restrictions for 28 days ...take effect on Saturday

The restrictions would not be as tight as the provincewide lockdown that was imposed in December

...The decision from Ford's cabinet on Wednesday followed the news that Ontario's hospitals have a record number of COVID-19 patients in intensive care units.

...Ontario has reported an average of about 2,300 new cases of COVID-19 per day over the past week... (post-Christmas province-wide lockdown: Dec. 21, the average number of new daily cases was 2,276.)

A key difference...is that...residents of long-term care have (now) largely been vaccinated against the disease.

...The count of new COVID-19 cases in Ontario schools for last week was the highest weekly total since the pandemic began. For the week of March 22, schools reported 1,222 cases among staff and students. The previous record was 999, during the final week of school before the Christmas holiday...

https://www.cbc.ca/news/canada/toronto/covid-19-ontario-emergency-brake-lockdown...

Good news (U.S.)! As long promoted by Harvard's Dr. Michael Mina, several antigen tests may now be used at-home. OTC, cheaper, no Rx nor medical supervision required, individuals can quickly ascertain their COVID status to quarantine accordingly:

FDA News Release
Coronavirus (COVID-19) Update: FDA Continues to Advance Over-the Counter and Other Screening Test Development
March 31, 2021

...Today, the agency authorized several tests for over-the-counter (OTC) use without a prescription when used for serial screening. In addition to the tests authorized for OTC use, one serial screening test was authorized for use in a point-of-care (POC) setting without a prescription, and an additional screening test was authorized for POC use with a prescription...

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-...

Eric Topol @EricTopol | 9:24 AM · Apr 1, 2021
New: 6 months follow-up of Pfizer vaccine trial in 46,000 participants
927 Infections: 850 placebo, 77 vaccine, 91% efficacy
22 severe infections: 21 placebo, 1 vaccine, 95% efficacy
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Ongoing trial shows Pfizer Covid-19 vaccine remains highly effective after six months
Maggie Fox | April 1, 2021

(CNN)The ongoing Phase 3 clinical trial of Pfizer/BioNTech's coronavirus vaccine confirms its protection lasts at least six months after the second dose, the companies said Thursday.

The question of how long vaccine protection lasts can only be answered once enough time has passed, and while six months of protection is a modest target, it's longer than previously known. The study is continuing and future updates may reveal more about how long and how strong this protection is.

The vaccine remains more than 91% effective against disease with any symptoms for six months, the companies said. And it appeared to be fully effective against the worrying B.1.351 variant of the virus, which is the dominant strain circulating in South Africa and which researchers feared had evolved to evade the protection of vaccines, the companies said...

https://www.cnn.com/2021/04/01/health/pfizer-covid-vaccine-efficacy-six-months-b...

>78 margd: contd.

So the question is how durable is one-dose mRNA protection in people previously infected with SARS-CoV-2? I should read the methods: how long ago were infections (one year at most?), how severe were the ensuing diseases?

Eric Topol @EricTopol | 9:14 AM · Apr 1, 2021:
Just published @NatureMedicine*:
One dose of mRNA vaccine in people with prior covid gets a robust antibody response, not augmented by 2nd dose
And, as expected, prior covid led to more 1st dose side-effects than no prior covid, 38 vs 25%, respectively.
Image ( https://twitter.com/EricTopol/status/1377610365085704196/photo/1 )

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* Joseph E. Ebinger et al. 2021. Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2 (Brief Communication). Nature Medicine (01 April 2021) https://www.nature.com/articles/s41591-021-01325-6

Abstract

In a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.

Eric Topol @EricTopol | 11:52 AM · Apr 1, 2021:
The immune response profile to covid is markedly different in the aged compared with children
Image ( https://twitter.com/EricTopol/status/1377650033688944641/photo/1 )
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Kevin J. Selva et al. 2021. Systems serology detects functionally distinct coronavirus antibody features in children and elderly. Nature Communications volume 12, Article number: 2037 (2021) https://www.nature.com/articles/s41467-021-22236-7

Abstract
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

Coronavirus digest: UK finds 30 blood clot cases after AstraZeneca jab
British regulators have found 30 cases involving rare blood clot events after the use of the AstraZeneca coronavirus vaccine — 25 more than was reported last month.

...Regulators in the UK have identified 30 cases involving rare blood clot events after the use of the AstraZeneca coronavirus vaccine. The new number is 25 more than was reported in the past.

Some countries have restricted the use of the AstraZeneca vaccine, as authorities investigate reports of rare, and in some cases severe, blood clots in patients who have received the jab.

However, officials believe that the benefits of the vaccine far outweigh any possible risk of blood clots.

Last month, the UK medicines regulator had registered five cases of a rare brain blood clot among the 11 million doses administered. The number has risen to 22 reports of cerebral venous sinus thrombosis, an extremely rare brain clotting ailment, as well as eight blood clotting cases associated with low blood platelets.

The regulators said they had received no such reports after the use of the BioNTech-Pfizer vaccine...

https://www.dw.com/en/coronavirus-digest-uk-finds-30-blood-clot-cases-after-astr...

Can Vaccinated People Spread the Virus? We Don’t Know, Scientists Say.
Researchers pushed back after the C.D.C. director asserted that vaccinated people “do not carry the virus.”
Apoorva Mandavilli | April 1, 2021

...The data suggest that “it’s much harder for vaccinated people to get infected, but don’t think for one second that they cannot get infected,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh.

In a television interview with MSNBC’s Rachel Maddow, Dr. Walensky referred to data published by the C.D.C. showing that one dose of the Moderna or Pfizer-BioNTech vaccine was 80 percent effective at preventing infection, and two doses were 90 percent effective.

That certainly suggested that transmission from vaccinated people might be unlikely, but Dr. Walensky’s comments hinted that protection was complete. “Our data from the C.D.C. today suggests that vaccinated people do not carry the virus, don’t get sick,” she said. “And that it’s not just in the clinical trials, it’s also in real-world data.”...

https://www.nytimes.com/2021/04/01/health/coronavirus-vaccine-walensky.html

>110 margd: Ontario, contd.

The report that prompted Ontario's April 1 restrictions:

COVID-19 Hospitalizations, ICU Admissions and Deaths Associated with the New Variants of Concern
Ontario COVID-19 Science Advisory Table* | March 29, 2021

...New variants of concern (VOCs) now account for 67% of all Ontario SARS-CoV-2 infections. Compared with early variants of SARS-CoV-2, VOCs are associated with a 63% increased risk of hospitalization, a 103% increased risk of intensive care unit (ICU) admission and a 56% increased risk of death due to COVID-19.

VOCs are having a substantial impact on Ontario’s healthcare system. On March 28, 2021, the daily number of new SARS-CoV-2 infections in Ontario reached the daily number of cases observed near the height of the second wave, at the start of the province-wide lockdown, on December 26, 2020.

The number of people hospitalized with COVID-19 is now 21% higher than at the start of the province-wide lockdown, while ICU occupancy is 28% higher (Figure 1). The percentage of COVID-19 patients in ICUs who are younger than 60 years is about 50% higher now than it was prior to the start of the province-wide lockdown.

Because the increased risk of COVID-19 hospitalization, ICU admission and death with VOCs is most pronounced 14 to 28 days after diagnosis, there will be significant delays until the full burden to the health care system becomes apparent...

Version 1.0 | https://doi.org/10.47326/ocsat.2021.02.18.1.0
https://covid19-sciencetable.ca/sciencebrief/covid-19-hospitalizations-icu-admis...

* The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario’s response.
________________________________________________

Ontario's Hospitals Facing Most Serious Crisis in Their History
Ontario Hospital Association | Apr 01, 2021

The Ontario Hospital Association welcomes the enhanced public health measures announced today by the Government of Ontario...

...Ontario hospitals are now caring for the highest number of patients with COVID-19 in critical care beds at one time, putting unprecedented strain on hospitals and their health care professionals and workers. Over the past two weeks, there has been a 41.7 per cent increase in hospitalizations, driven largely by new variants of concern. There are now 430 patients in intensive care units (ICUs) with 43 new admissions yesterday alone. In contrast to the first two waves, many of these patients are younger, and many do not have any prior health care concerns. Provincial modelling projects that a scenario of 700 patients in ICU is possible by April 18. Should that occur, the cost to human health and to the ability of hospitals to provide equitable access to critical care and all other health services will be devastating...

...At this moment, the OHA makes three health policy recommendations.
(1) First, it's imperative that we get vaccines into the arms of those in the hardest-hit and most vulnerable communities...
(2) Second, a provincial campaign is needed as soon as possible to improve vaccine confidence and increase uptake of COVID-19 vaccines...
(3)Third, sick pay for essential workers is needed immediately to help stop community spread of COVID-19, particularly among essential workers...

https://www.newswire.ca/news-releases/ontario-s-hospitals-facing-most-serious-cr...

(Via 2wonderY, #61 in Big Pharma thread)

PFIZER, MODERNA, AND other coronavirus vaccine makers have said repeatedly that they intend to hike prices on vaccines as early as this year, as the potential need for additional booster shots and future demand could lead to an unprecedented financial windfall.

One estimate projects that if Pfizer raised the price of its coronavirus vaccine from $19.50 to $175 per dose, as one Pfizer executive recently suggested, and if every adult American were to take it, the cost would be $44.7 billion — nearly 10 percent of all U.S. drug spending.

But the federal government, which funded crucial biomedical research to develop the patented messenger RNA technology behind the leading Covid-19 vaccines, is on the verge of eliminating a legal mechanism to control the prices of key medical products, including vaccines.

Next week, the National Institute of Standards and Technology, or NIST, will wrap up a comment period to modify the rules governing the Bayh-Dole Act, a law that regulates the transfer of federally funded inventions into commercial property. Under the current interpretation of the law, the government may “march in” and suspend the use of patents developed via government-funded inventions if it determines that the products are excessively priced.

IN THE TWILIGHT weeks of Donald Trump’s presidency, his administration released a NIST rule designed to undercut the Bayh-Dole Act and weaken the government’s authority to march in and seize control of a patent when drugmakers fail to make medicine “available to the public on reasonable terms.”

https://theintercept.com/2021/04/02/covid-vaccine-price-hikes/
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margd: those interested have three days to comment.
https://www.regulations.gov/document/NIST-2021-0001-0001/comment

Do vaccines lower transmission? YES, absolutely. How much? By a lot—75% to 94% in recent studies. Do vaccines completely eliminate any and all transmission? NO. That is why we still need to mask after vaccinating until cases are very low or zero.
Inline image--table ( https://twitter.com/DrEricDing/status/1377861074293260288/photo/1 )

Also, it’s not always 75-94% either. For AstraZeneca and asymptomatic #B117 it’s much lower for efficacy ~29% (with wide error bars). https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00628-0/fullt...

-Eric Feigl-Ding @DrEricDing | 1:50 AM · Apr 2, 2021
_________________________________________

Peter Hamby @PeterHamby · 21h:
“Vaccinated people do not carry the virus"
https://nymag.com/intelligencer/2021/03/cdc-data-suggests-vaccinated-dont-carry-...

Eric Topol @EricTopol | 5:09 PM · Apr 1, 2021:
Not exactly. You can be vaccinated and carry the virus (carrier).
But if the viral load is so low you can't transmit (not a transmitter)
spread is blocked and we move onto the pandemic exit ramp.

Barliz Waissengrin et al. 2021. Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors (Comment). The Lancet Oncology. Published:April 01, 2021 DOI:https://doi.org/10.1016/S1470-2045(21)00155-8 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00155-8/fullt...

...The data we present here provide, for the first time, a reassuring safety signal regarding the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors. Considering the high mortality due to COVID-19 in patients with cancer who are being treated, our data support current guidelines and call for vaccination of patients being treated with immune checkpoint inhibitors, especially during pandemic surges.

How travelers who test positive for Covid can (legally) fly home fast
Monica Buchanan Pitrelli | Apr 1 20212:39 AM EDT

...Covac Global transports people home if they have been diagnosed with Covid while traveling domestically or abroad.

The team behind the company also operates a crisis response firm called HRI, which conducts security risk and “traditional medical” evacuations...Travelers have to sign up before they leave home.

Memberships are available to residents of the United States and Canada but will open to all nationalities starting in May, said Thompson. Rates start at $675 for 15 days of coverage, which can be used over the course of 12 months, and benefits begin two weeks after signing up.

...Private medical evacuation for Covid is expensive, said (CEO Ross) Thompson, adding that transports can cost upwards of $200,000.

While there are no restrictions on travel destinations, memberships don’t cover travelers on cruise ships or who attend large-scale events.

What about CDC test requirements?

The Centers for Disease Control and Prevention require air passengers to present a negative Covid test (or proof of recovery) before entering the United States.

“Extremely limited” exemptions are allowed for emergency travel, according to the CDC’s website...Medical travel must be via certified air ambulance, under the care and recommendation of a physician, and detailed paperwork must be filed with the CDC, U.S. Department of State and Department of Homeland Security...

https://www.cnbc.com/2021/04/01/how-to-fly-home-if-you-test-positive-for-covid.h...

For greater vaccine equity, first fix these misconceptions
Philip Schellekens Friday, April 2, 2021

A global snapshot of vaccine inequity
Don’t penalize developing countries for a ‘less visible’ pandemic
Prioritize the global priority group, worry about universal coverage later

Connect vaccine equity to a broader development agenda
A final misconception relates to vaccine equity more broadly. It is worth remembering the world’s performance against the
Millennium Development Goals. We met the goal of reducing income poverty five years ahead of time. But the progress on all other goals—the non-income dimensions of development including health, education, sanitation, and others—were much more incomplete and heterogeneous. These dimensions represented the persistent development bottlenecks that left countries behind and motivated the broader 2030 agenda

For at least three reasons, the call for #VaccinEquity needs to be connected to this broader development agenda. First, because fixing vaccine hoarding in rich countries and distributing them more equitably across countries will not be sufficient to fix vaccine inequity on its own. Inequities and deficiencies across the broader supply chain across and within borders need to be considered. Second, the vaccine equity movement must call attention to and extend greater solidarity with other inequities in global health and development. Third, since pandemics are likely to occur again, we must seize the opportunity to break the cycle of panic and neglect and scale up pandemic preparedness.

https://www.brookings.edu/blog/future-development/2021/04/02/for-greater-vaccine...

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Fingers crossed:

Eric Feigl-Ding @DrEricDing | 3:24 AM · Apr 3, 2021
13) need to goto sleep... but I’ve been talking to people in DC. There is hope something can be done to help the people of Brazil hopefully soon. Stay tuned and stay safe my friends.

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Global Map: Share of Covid-19 Cases that are positive
Jan 6, 2020 - April 1, 2021
Our World in Data | last updated April 2, 2021
https://ourworldindata.org/grapher/positive-rate-daily-smoothed

Pfizer, Moderna, J&J side effects %:

One chart shows which vaccine side effects you can expect based on your age, manufacturer, and dose
Aria Bendix and Joanna Lin Su | April 3, 2021
https://www.businessinsider.com/covid-vaccine-side-effects-dose-pfizer-moderna-j...

The Biden administration puts Johnson & Johnson in charge of a Baltimore plant that ruined millions of doses of its vaccine.
NYT | April 3, 2021

...extraordinary move by the Department of Health and Human Services will leave the Emergent BioSolutions facility solely devoted to making the Johnson & Johnson single-dose vaccine and is meant to avoid future mix-ups (with AstraZeneca two-dose vaccine), according to two senior federal health officials.

...Federal officials are worried that the (J&J / AZ) mix-up will erode public confidence in the vaccines...

AstraZeneca said in a statement that it would work with the Biden administration to find an alternative site. (...the company would continue making AstraZeneca doses until it received a contract modification from the federal government...)

...in the past, the Food and Drug Administration had a rule to prevent such mishaps by not allowing a facility to make two live viral vector vaccines, because of the potential for mix-ups and contamination.

...Health and Human Services Department was discussing working with AstraZeneca to adapt its vaccine to combat new coronavirus variants.

...Emergent’s Baltimore facility is one of two facilities that were built with taxpayer support...Last June, the government paid Emergent $628 million to reserve space there as part of Operation Warp Speed, the Trump administration’s fast-track initiative to develop coronavirus vaccines.

Johnson & Johnson and AstraZeneca both contracted with Emergent to use the space. Both companies’ vaccines are so-called live viral-vector vaccines, meaning they use a modified, harmless version of a different virus as a vector, or carrier, to deliver instructions to the body’s immune system...

https://www.nytimes.com/live/2021/04/03/world/covid-vaccine-coronavirus-cases

Hope finding survives peer review: "We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351..."

P.1 variant was first reported in Brazil, and now has a foothold in British Columbia (including NHL hockey team, Canucks).
B.1.351 was first reported in South Africa.

Wanwisa Dejnirattisai et al. 2021. Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2. BioRxiv (March 19, 2021). 47 p. https://doi.org/10.1101/2021.03.12.435194 https://www.biorxiv.org/content/10.1101/2021.03.12.435194v2.full.pdf

Preprint. Not yet reviewed.

Summary
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, 61K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD (receptor binding domain) impact neutralisation. Monoclonal antibody neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 lightchain to largely restore neutralization potency to a major class of public antibodies....

UK: long COVID impacts healthcare, schools, care:

Strain on (UK's) NHS as tens of thousands of staff suffer long Covid
Denis Campbell | 3 Apr 2021

At least 122,000 NHS personnel have (long COVID), the Office for National Statistics disclosed in a detailed report that showed 1.1 million people in the UK were affected by the condition. That is more than any other occupational group and ahead of teachers, of whom 114,000 have it.

Patient care is being hit because many of those struggling with long Covid are only able to work part-time, are too unwell to perform their usual duties, or often need time off because they are in pain, exhausted or have “brain fog”...

...The ONS found about 30,000 social care workers also had long Covid, which could affect staffing levels in care homes and among services that provide at-home care...

https://www.theguardian.com/society/2021/apr/03/nhs-feels-strain-tens-thousands-...

See article for visualization of outbreak traced to poorly ventilated restaurant: "This outbreak involved ten infected persons in three families (A, B, C). All ten persons ate lunch at three neighboring tables at the same restaurant on January 24, 2020. None of the restaurant staff or the 68 patrons at the other 15 tables became infected. During this occasion, the measured ventilation rate was 0.9 L/s per person. No close contact or fomite contact was identified, aside from back-to-back sitting in some cases. Analysis of the airflow dynamics indicates that the infection distribution is consistent with a spread pattern representative of long-range transmission of exhaled virus-laden aerosols. Airborne transmission of the SARS-CoV-2 virus is possible in crowded space with a ventilation rate of 1 L/s per person."

Yuguo Liah et al. 2021. Probable airborne transmission of SARS-CoV-2 in a poorly ventilated restaurant. Building and Environment
Volume 196, June 2021, 107788. https://doi.org/10.1016/j.buildenv.2021.107788 https://www.sciencedirect.com/science/article/pii/S0360132321001955?via%3Dihub#a...

Highlights

• This outbreak involved ten infected persons in three families.
• Full video recording at time of infection allows restoration of the scene.
• Time-averaged ventilation rates were only 0.9 L/s per person in the restaurant.
• Insufficient ventilation played a role in this outbreak of COVID-19.

Abstract
Although airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized, the condition of ventilation for its occurrence is still being debated. We analyzed a coronavirus disease 2019 (COVID-19) outbreak involving three families in a restaurant in Guangzhou, China, assessed the possibility of airborne transmission, and characterized the associated environmental conditions. We collected epidemiological data, obtained a full video recording and seating records from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the index case. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer gas concentration decay method. This outbreak involved ten infected persons in three families (A, B, C). All ten persons ate lunch at three neighboring tables at the same restaurant on January 24, 2020. None of the restaurant staff or the 68 patrons at the other 15 tables became infected. During this occasion, the measured ventilation rate was 0.9 L/s per person. No close contact or fomite contact was identified, aside from back-to-back sitting in some cases. Analysis of the airflow dynamics indicates that the infection distribution is consistent with a spread pattern representative of long-range transmission of exhaled virus-laden aerosols. Airborne transmission of the SARS-CoV-2 virus is possible in crowded space with a ventilation rate of 1 L/s per person.

Cornerstones of care (physicians' best strategies):
https://twitter.com/ScienceMagazine/status/1378927905066074112/photo/1

https://www.sciencemag.org/news/2021/03/how-do-you-treat-coronavirus-here-are-ph...

U.S.: Not true that lockdowns increased suicides. In 2020, lower than in the previous three years.

Elizabeth Jacobs, PhD (epidemiologist) @TheAngryEpi | 6:32 PM · Apr 4, 2021
Politicians told us repeatedly that lockdowns were causing increased numbers of deaths by suicide. We kept asking to see the data. Now, we have it, and apparently, this was not true. In 2020, deaths by suicide were lower than in the previous three years.
Image-table ( https://twitter.com/TheAngryEpi/status/1378837935689146368/photo/1 )
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Farida B. Ahmad and Robert N. Anderson. 2021.The Leading Causes of Death in the US for 2020 (Viewpoint). JAMA. Published online March 31, 2021. doi:10.1001/jama.2021.5469 https://jamanetwork.com/journals/jama/fullarticle/2778234

HexaPro, modified version of the SARS-CoV-2 spike protein, with its six key alterations (amino acid proline)--cheap and easily made (chicken eggs) vaccine--shows great promise. The University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties. Worthwhile read:

Researchers Are Hatching a Low-Cost Coronavirus Vaccine
A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.
Carl Zimmer | April 5, 2021

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam . The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

...First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

...(Jason McLellan, now at U Texas Austin) also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties...

https://www.nytimes.com/2021/04/05/health/hexapro-mclellan-vaccine.html

Darn.

Jeremy Kamil (Virologist) @macroliter | 10:17 AM · Apr 2, 2021:
Our latest work with @VirusWhisperer shows that
the B.1.351 variant easily escapes Sputnik V vaccine elicited neutralizing antibodies.

Satoshi Ikegame et al. 2021. Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants. MedRxiv. doi: https://doi.org/10.1101/2021.03.31.21254660 https://www.medrxiv.org/content/10.1101/2021.03.31.21254660v1

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

ABSTRACT
The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

Large study finds no link between blood type and COVID-19 severity or risk
Medical News Today | 04/06/2021

A new review* of almost 108,000 patients concludes there is no link between blood type and COVID-19 risk or severity. The findings appear in the journal JAMA Network OpenTrusted Source.

...“We found no ABO associations with either disease susceptibility or severity,” write the researchers. “Given the large and prospective nature of our study and its strongly null results, we believe that important associations of SARS-CoV-2 and COVID-19 with ABO groups are unlikely,” they conclude.

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

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* Jeffrey L. Anderson et al. 2021. Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population. JAMA Netw Open. Apr 5 2021;4(4):e217429. doi:10.1001/jamanetworkopen.2021.7429

Canada’s Vaccine Mess
Canada has universal health care and millions of doses on order. So why are so few of its citizens vaccinated?
Tracey Lindeman | April 6, 2021
https://www.theatlantic.com/international/archive/2021/04/canada-vaccine-rollout...
____________________________________________________

Vaccinating Africa: Countries struggle to deliver the few shots they've got
Dave Lawler | April 5, 2021
https://www.axios.com/african-countries-struggle-vaccine-distribution-c09480b3-2...
____________________________________________________

The U.S. Should Vaccinate the World
And let’s get it done this year. It’s in our own best interest.
Dalibor Rohac | April 6, 2021
https://thebulwark.com/the-u-s-should-vaccinate-the-world/

>130 margd: >131 margd:

Eric Topol @EricTopol | 3:58 PM · Apr 2, 2021:
The importance of the 2-P (proline) substitution in the spike protein in vaccines may be playing out:
1. Astra Zeneca (no 2-P) vs B.1.351 trial without efficacy
2. Sputnik V (no 2-P) vs B.1.351 new preprint https://medrxiv.org/content/10.1101/2021.03.31.21254660v1

Image ( https://twitter.com/EricTopol/status/1378074337681399808/photo/1 )
Image ( https://twitter.com/EricTopol/status/1378074337681399808/photo/2 )

___________________________________________________

Eric Topol @EricTopol | 1:09 PM · Apr 6, 2021:
Reassuring new data for 2 inactivated virus vaccines, Sinovac and Sinopharm, developed in China (no 2-P substitution),
now in wide use,
against both the B.1.1.7 (UK) and B.1.351 (SA) variants
Image ( https://twitter.com/EricTopol/status/1379481274826416130/photo/1 )*
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* Guo-Lin Wang et al. 2021. Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization. NEJM April 6, 2021.
DOI: 10.1056/NEJMc2103022 https://nejm.org/doi/full/10.1056/NEJMc2103022?query=featured_home

...Our findings suggest that B.1.1.7 showed little resistance to the neutralizing activity of convalescent or vaccinee serum, whereas B.1.351 showed more resistance to the neutralization of both convalescent serum (by a factor of 2) and vaccinee serum (by a factor of 2.5 to 3.3) than the wild-type virus. Most of the vaccinee serum samples that were tested lost neutralizing activity, a finding that was consistent with the results of other recent studies of neutralization by convalescent serum or serum obtained from recipients of messenger RNA or BBIBP-CorV (SinoPharm) vaccines....

Eric Topol @EricTopol | 4:49 PM · Apr 2, 2021:
A concern raised about delaying the 2nd vaccine dose is the potential to promote immune escape, new mutations.
A new @NatRevImmunol essay* argues against that possibility (may even be the opposite)
Image ( https://twitter.com/EricTopol/status/1378087192954691585/photo/1 )
---------------------------------------------------

* Sarah Cobey et al. 2021. Concerns about SARS-CoV-2 evolution should not hold back efforts to expand vaccination. Nature Reviews Immunology (Apr 1 2021) https://www.nature.com/articles/s41577-021-00544-9

Abstract

When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine-escape variants, ultimately undermining vaccine effectiveness. We argue that, although this is possible, preliminary evidence instead suggests such strategies should slow the rate of viral escape from vaccine or naturally induced immunity. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence of efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.

Most kids with serious inflammatory illness had mild COVID
LINDSEY TANNER | April 6, 2021
https://www.startribune.com/most-kids-with-serious-inflammatory-illness-had-mild...

Somewhere I read this is 1 in 10,000.

246 fully vaccinated Michiganders got COVID-19 between January and March, state reports
Kristen Jordan Shamus | April 6, 2021

... three have died...

...Dr. Paul Thomas, a family medicine physician in Detroit who started Plum Health (said)...People should keep in mind that the 246 breakthrough cases occurred among the more than 1.8 million Michiganders who are fully vaccinated...

"That breaks down to 0.0144% of those who have gotten the vaccine have come down with a breakthrough infection," Thomas said. "So that means that the vaccine is 99.99% effective in preventing infection.

https://www.freep.com/story/news/local/michigan/2021/04/06/vaccinated-covid-19-c...

>137 margd: Take home is the huge number of lives saved, and health consequences averted. The point is made in the article. Serious Covid cases after vaccination are very rare, by orders of magnitude compared to no vaccination.

>138 stellarexplorer:

Thanks. And doesn't it also underline the dynamic that this is not only about individuals, about protecting myself, but is about community health, protecting the greatest number of people?

Why the AZ vaxxes sent to Mexico and Canada had to be "loans":

“We Are Hoarding”: Why the U.S. Still Can’t Donate COVID-19 Vaccines to Countries in Need
Thanks to America First–style contracts negotiated by the Trump administration and an alarming uptick in domestic cases, the urgent work of planning to vaccinate the rest of the world is stuck in limbo.
Katherine Eban | April 6, 2021

...For officials hoping to finally pivot from domestic to international vaccination strategy, there was another major catch...The contracts the Trump administration signed with the vaccine manufacturers prohibit the U.S. from sharing its surplus doses with the rest of the world. According to contract language Vanity Fair has obtained, the agreements with Pfizer, Moderna, AstraZeneca, and Janssen state: “The Government may not use, or authorize the use of, any products or materials provided under this Project Agreement, unless such use occurs in the United States” or U.S. territories.

The clauses in question are designed to ensure that the manufacturers retain liability protection, but they have had the effect of projecting the Trump administration’s America First agenda into the Biden era. “That is what has completely and totally prohibited the U.S. from donating or reselling, because it would be in breach of contract,” said a senior administration official involved in the global planning effort. “It is a complete and total ban. Those legal parameters must change before we do anything to help the rest of the world.”

...The impasse is especially frustrating because the Biden team’s global ambitions go beyond donating money or surplus vaccines. Vanity Fair has learned that the administration is quietly considering plans to have the U.S. serve as a major manufacturer of affordable, high-quality COVID vaccines for the entire world—a role typically reserved for lower-cost countries such as India...

https://www.vanityfair.com/news/2021/04/why-the-us-still-cant-donate-covid-19-va...

The Lancet Psychiatry: Largest study to date suggests link between COVID-19 infection and subsequent mental health and neurological conditions (News Release)
The Lancet | 6-Apr-2021

Research News
Study* using electronic health records of 236,379 COVID-19 patients mostly from the USA estimates that one in three COVID-19 survivors (34%) were diagnosed with a neurological or psychiatric condition within six months of infection.

Anxiety (17%) and mood disorders (14%) were the most common. Neurological diagnoses such as stroke and dementia were rarer, but not uncommon in those who had been seriously ill during COVID-19 infection. For example, of those who had been admitted to intensive care, 7% had a stroke and almost 2% were diagnosed with dementia.

These diagnoses were more common in COVID-19 patients than in flu or respiratory tract infection patients over the same time period, suggesting a specific impact of COVID-19.

Authors say their findings should aid service planning and highlight need for ongoing research...

https://eurekalert.org/pub_releases/2021-04/tl-tlp040621.php

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"Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19."

* Maxime Taquet et al. 2021. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry (April 06, 2021) DOI:https://doi.org/10.1016/S2215-0366(21)00084-5 https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00084-5/fullt...

Summary
Background...
Methods...

Findings
Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% ..., with 12·84% ... receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42%... and for a first diagnosis was 25·79% ... Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% ... for intracranial haemorrhage, 2·10% ... for ischaemic stroke, 0·11% ... for parkinsonism, 0·67% ... for dementia, 17·39% ... for anxiety disorder, and 1·40% ... for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% ... for intracranial haemorrhage, 6·92% ... for ischaemic stroke, 0·26% ... for parkinsonism, 1·74% ... for dementia, 19·15% ... for anxiety disorder, and 2·77% ... for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio (HR) 1·44...for any diagnosis; 1·78...for any first diagnosis) and those who had other respiratory tract infections (1·16...for any diagnosis; 1·32...for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58...for any diagnosis; 2·87...for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events.

Interpretation
Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings...

Table 2. https://twitter.com/TheLancet/status/1379555514955235334/photo/1

>139 John5918: Yes, totally agree and that logic works for me. But for those only concerned about their own well-being, the argument in favor of vaccination is also convincing.

New findings in COVID-related kids' syndrome, Kawasaki disease
Mary Van Beusekom | Apr 06, 2021

...Low blood pressure, shock, heart dysfunction

In the first study, published in JAMA Pediatrics, a team led by researchers from the US Centers for Disease Control and Prevention (CDC) used lab data to compare geographic and temporal distribution of MIS-C from March 2020 to January 2021 with that of COVID-19 over the same period.

...Delayed immune response to coronavirus

...In a commentary in the same journal, Jennifer Blumenthal, MD, and Jeffrey Burns, MD, MPH, both of Boston Children's Hospital, said that the study findings show that the lack of prior coronavirus symptoms, especially in younger children, shouldn't reassure pediatricians that MIS-C hasn't affected their hearts.

...Kawasaki disease spread likely airborne

Published in JAMA Network Open, the second study was led by researchers at Fukuoka Children's Hospital in Japan to determine the role of droplet versus contact transmission of KD....

https://www.cidrap.umn.edu/news-perspective/2021/04/new-findings-covid-related-k...

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Ermias D. Belay et al. 2021.Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic. JAMA Pediatr. Published online April 6, 2021. doi:10.1001/jamapediatrics.2021.0630 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2778429

Abstract
...Conclusions and Relevance
In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

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

Jennifer A. Blumenthal and Jeffrey P. Burns. 2021. Epidemiology of Multisystem Inflammatory Syndrome in Children: A Step Closer to Understanding Who, Where, and When (Editorial). JAMA Pediatr. Published online April 6, 2021. doi:10.1001/jamapediatrics.2021.0638 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2778430
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Takuya Hara et al. 2021. Assessment of Pediatric Admissions for Kawasaki Disease or Infectious Disease During the COVID-19 State of Emergency in Japan. JAMA Netw Open. 2021;4(4):e214475. doi:10.1001/jamanetworkopen.2021.4475 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778178

Abstract
...Conclusions and Relevance In this study, the significantly increased incidence of KD compared with respiratory tract and gastrointestinal infections during the COVID-19 state of emergency suggests that contact or droplet transmission is not a major route for KD development and that KD may be associated with airborne infections in most cases...

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

Xavier Rodó and Alejandro Fontal. 2021. COVID-19 Pandemic Sets New Clues on the Transmission Pathways in Kawasaki Disease (Invited Commentary). JAMA Netw Open. Apr 6, 2021;4(4):e214624. doi:10.1001/jamanetworkopen.2021.4624 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778186

Eric Topol @EricTopol · 12:25 PM · Apr 7, 2021:
Graphic by @alex_freeman shows the UK calculation of benefit vs harm by age group
Image ( https://twitter.com/EricTopol/status/1379832662685229058/photo/1 )

Henrik Rasmussen
I find that comparison skewed in favour of the vaccine. For a start, the majority of CVST incidents were in women, less likely to die from Covid, so the statistics need to be performed by gender. The equilibrium age for women will then be higher than suggested by this graph.

Second, the comparison with ICU admissions is not necessarily appropriate either. After all, 90% (?) of those admitted survive, while CVST fatality appears to be higher than 10%.

Sebastian Drolshagen
Great. Many thanks for sharing this! Important: Graphic is for incidence of 6 / 10.000. For most of Europe, it‘s actually much higher (much) more benefit from AZ vaccination

>137 margd: Somewhere* I read this is 1 in 10,000: "246 fully vaccinated Michiganders got COVID-19 between January and March, state reports"

* zeynep tufekci (UNC prof) zeynep | 1:30 PM · Apr 6, 2021:

Common misleading headline/frame.
Denominator is 1,800,000. That's ~1 in 10,000 breakthrough cases.
Two, such cases are milder.
Three, rare deaths, among the elderly happen at that scale. *Common colds* cause deadly outbreaks in nursing homes. And, only two were fully-vaccinated...

>145 margd: Thanks for the update on that one!

>140 margd: Why the U.S. Still Can’t Donate COVID-19 Vaccines to Countries in Need

Christopher G. Moore @cgmooreauthor | 10:07 AM · Apr 7, 2021
The US Embassy in question takes a six month lease in a designated area of a clinic or hospital (in cooperation with local authorities) and then transfer the vaccine as training program for local doctors and nurses.

Quote Tweet
Eric Feigl-Ding @DrEricDing
NEW—We now know why US cannot share its #COVID19 vaccines with the world—Trump WH had forced legal contracts that blocks US doses by Pfizer, Moderna, AstraZeneca, J&J from being donated. Hence Canada & Mexico only got “loans”...

2) And not just US citizens would be eligible. But maybe there can be a section of US embassies / consulates that can offer it to non-Americans too theoretically if they came to the Embassy. There is no “citizens only” clause, just a “US territory” clause.

3) In addition, US military bases abroad. And maybe US entry Pre-clearance zones in which are considered as having “entered the US”.

I know embassies and military bases are still consider foreign soil, but they are under official US sovereign control. It’s grey area for sure.

4) Is there precedent for this? YES! Russia prohibits the use of Us vaccines in Moscow. So what does the US Embassy in Moscow do? It is airlifting vaccines to the US Embassy and administering US approved vaccines on embassy grounds!

This is *precedent*!

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:D

Sharmine Narwani @snarwani | 12:50 PM · Apr 7, 2021:
What about sending each vaccine with a bag of Texas dirt. One could stand on it and be vaccinated. And nobody in Texas will miss even a gram of it.

Officer Eugene Goodman is a gd hero! @Amberly744 | 10:59 AM · Apr 7, 2021
Diplomatic cars are considered sovereign territories right? Put a team of doctors in some limos with diplomatic plates, send them on a road trip. Kind of like a reverse drive thru.

Nick Casey @NickCasey
Just use a bus/RV. Make the drug companies sue of they don't like it.

Eric Topol @EricTopol | 5:01 PM · Apr 7, 2021:
Best V3 news for today (vaccine-virus-variants)
1. Prior covid + mRNA vaccine (@BioNTech_Group) =
very high levels of neutralizing antibodies against B.1.351 (South Africa) and P.1 (Brazil) variants @NEJM (N=6)
Image ( https://twitter.com/EricTopol/status/1379902220758437889/photo/1 )
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Eric J. Rubin et al. 2021. Audio Interview: Antibody Responses to Natural Infection and Vaccination. N Engl J Med Apr 8, 2021; 384:e65 DOI: 10.1056/NEJMe2105969 https://www.nejm.org/doi/full/10.1056/NEJMe2105969?query=featured_home
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2. The mRNA vaccine (@moderna_tx) and @Novavax elicit high levels of neutralizing antibodies versus the B.1.429 (California) variant, similar to B.1.17 (UK) which means not very much immune evasion @NEJM
Image ( https://twitter.com/EricTopol/status/1379902226756333569/photo/1 )
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Xiaoying Shen et al. 2021. Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351 (Correspondence). NEJM April 7, 2021
DOI: 10.1056/NEJMc2103740 https://nejm.org/doi/full/10.1056/NEJMc2103740?query=featured_home
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3. 3. Neutralizing antibodies against the B.1.351 (South African, 501Y.V2) variant cross-react to the others, telling us if we need a booster vaccine by incorporating this code, it should be quite effective (501Y.V3 = P.1, Brazil) @NEJM
Image ( https://twitter.com/EricTopol/status/1379902231948845057/photo/1 )
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Thandeka Moyo-Gwete et al. 2021. Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 (B.1.351) (Correspondence). NEJM April 7, 2021 DOI: 10.1056/NEJMc2104192 https://nejm.org/doi/full/10.10
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4. Why is this all very good news?
—Prior covid is like the 1st shot, a primer for the immune response
—1st data in patients with mRNA vaccine vs. B.1.351 and P.1 and they look very solid (small N) for very high levels of neutralizing antibodies
—California variant responds well

Most U.S. infections are now caused by a contagious new virus variant, the C.D.C. says.
C.D.C. Says U.K. Variant Is Now Most Common in the U.S.
Sheryl Gay Stolberg | April 7, 2021

A highly infectious variant of the coronavirus that was first identified in Britain has now become the most common source of new infections in the United States, the director of the Centers for Disease Control and Prevention said Wednesday — a worrisome development that comes as officials and scientists warn of a possible fourth virus surge.

Federal health officials said in January that the B.1.1.7 variant, which began surging in Britain in December and has since slammed Europe, could become the dominant source of coronavirus infections in the United States, leading to a wrenching increase in cases and deaths.

While new cases, hospitalizations and deaths have declined from their peaks in January, new infections have increased after plateauing. Further progress in reducing new cases has stalled, hospitalizations have leveled off, and deaths remain near an average of about 800 a day, according to a New York Times database.

The average number of new cases has reached nearly 65,000 a day, as of Tuesday, concentrated mostly in metro areas in Michigan as well as the New York City region. That’s up 19 percent from the figure two weeks ago...

https://www.nytimes.com/2021/04/07/us/covid-variant-infection.html

Covid: UK vaccine rollout 'breaking link' between infections and death (BBC)

The UK's vaccination programme is beginning to break the link between Covid-19 cases and deaths, scientists tracking the epidemic have said. A study found infections had fallen by roughly two-thirds since February, but have begun to level off...

Didn't RickHarsch hail from that part of the world? Haven't heard from him lately?
Rastaphrog? (He/she worked in grocery store.)
Hope they're okay, that they just found other ways to occupy time?

Eric Feigl-Ding @DrEricDing | 4:19 AM · Apr 8, 2021
Eastern Europe and Balkans have insane levels of #COVID19 mortality. For context, Brazil’s high mortality rate is around 13/mil.

Hungary
Bosnia
North Macedonia
Bulgaria
Slovakia
Montenegro
all have higher death rates than even Brazil!!
(7 day-daily avg)

Image ( https://twitter.com/DrEricDing/status/1380072795707674629/photo/1 )