Coronavirus Update 2-3

Recent Developments

February 3, 2021

“One conclusion is that the disease may be seasonal, like the flu. This is very relevant to what we should expect from now on after the vaccine controls these first waves of C19.”
Gustavo Caetano-Anollés, professor in the Department of Crop Sciences

“It’s likely that wearing masks and taking other measures to prevent transmission, especially in the winter months, will become an ongoing part of our lives.”
Christopher Murray, director of Institute for Health Metrics and Evaluation at the University of Washington

“There’s no data indicating that wearing two masks is going to make a difference.” Dr. Fauci, one week after saying that “if one mask serves as a physical barrier, it makes common sense, and certainly can’t hurt and might help to wear two masks.” Note: No comment yet from Dr. Fauci as to whether 3 masks are more effective than 2, or 3 more effective than 4….

Index

Navigational Tips: Except for the stories listed under Linked Stories, all of the stories listed below are included in this update. And to the extent available, we have embedded links in the title of the stories to the extent available so that you can quickly jump to the original story on the internet if you want by clicking on the title. If you reading the Word document, you can jump to a section by holding down the control key+clicking on the title of the section.

Highlighted stories includes information we found interesting. An (!) indicates a story that includes new, promising/breakthrough or unexpected/surprising information. A (_*) indicates information that may be useful in connection with your plans and preparations regarding the coronavirus and C19. And © indicates that a story contains information that may contradict or be inconsistent with other information.

A. Pandemic Headlines

B. Numbers & Trends

Cases & Tests
Deaths
Top 5 States in Cases, Deaths, Hospitalizations, ICU Patients & Positivity
Latest Covid Surge Appears to Flame Out Even in Worst Hot Spots
US Vaccinations

C. New Variants (Mutations) of Coronavirus

D. New Scientific Findings & Research

E. Vaccines & Testing

F. Improved & Potential Treatments

G. Concerns & Unknowns

K. Projections & Our (Possible) Future

L. Practical Tips & Other Useful Information

M. Johns Hopkins COVID-19 Update

N. Linked Stories

Notes:

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A. Pandemic Headlines

(In no particular order)

‘Worrying’ new mutation detected in UK COVID-19 variant
A study shows the variant spreading rapidly in Britain might make vaccines less effective
Study finds COVID-19 reinfection is ‘common’ among young people
Resurgence of COVID-19 in the United States was largely driven by adults between the ages of 20 and 49
Lack of ICU beds tied to thousands of excess COVID-19 deaths
26.5 million Americans have been vaccinated
Vaccinations are slowly picking up speed in the U.S., averaging about 1.3 million doses per day over the past week
US has administered vaccination shots at faster rate than any other country
US COVID Vaccinations Top Cases For First Time… But A Majority Of Americans Still Remain Skeptical
Johnson & Johnson could deliver 100 million COVID vaccines by June
Feds shipping 1 million COVID vaccines to pharmacies nationwide
A third of Americans say they are unlikely or hesitant to get COVID-19 vaccine
More than half of Americans would refuse or delay getting the COVID vaccine
LA COVID-19 Vaccinations Delayed By Protesters
CDC requires wearing of face masks while on public transportation and at transportation hubs
Germany’s BioNTech said it would make 75 million additional doses of its vaccine for the European Union
Russia’s “Sputnik V” Vaccine 92% Effective Against “Symptomatic” COVID Cases
New data on the AstraZeneca-Oxford vaccine lend support for delaying its second doses
Iran will receive a shipment of the Russian coronavirus vaccine, the Islamic Republic’s first
Dozens of countries have no plan to vaccinate refugees. That could leave everyone at risk.
California aims to speed up vaccines
TSA agents can deny entry to maskless travelers after Biden executive order
Study finds those who’ve had COVID-19 may only need one dose of vaccine
Top NY Virus Officials Quit As Cuomo Wages “War” With His Own Health Department
Top NY Democrat wants state legislature to reconsider NY Gov. Cuomo’s COVID-19 powers
Florida has the most cases of the UK COVID-19 variant
US Secretary of State: China’s handling of COVID-19 makes it a ‘profound problem’
Scotland extends lockdown until end of February
US new cases lowest since November
England, Wales see second-highest deaths
Israeli cases rise despite vaccinations, lockdowns
Japan set to extend state of emergency for another month
Merkel promises a vaccine dose for every German by September
Italy begins unwinding lockdown
Portugal reports nearly half of all its COVID-19 deaths in January
Portugal has Europe’s highest death rate and is desperately short of hospital beds
China reports 30 new cases, lowest in a month
Thousands Of Maskless Orthodox Jews Ignore Israeli Lockdown To Attend Funerals
Thousands Of Fake COVID-19 Vaccines Circulating In China
2 million Australians forced into five-day “full lockdown” after a single hotel security guard tests positive for COVID. And the arrests have already started.
Australians in lockdown are driven from their homes by a wildfire
‘Don’t be afraid’: Polish restaurants, gyms defy ‘unenforceable’ restrictions
Hong Kong Threatens to Knock Down Doors to Force Covid Tests
1 in 3 adults anxious, depressed
WWII vet who raised almost $45M for front-line workers dead after COVID-19 battle
Moderna proposes filling vials with 15 doses instead of 10
Pandemic Baby Boom Turned Out to Be Bust Despite Lockdown
Nearly half of US COVID-19 case, vaccination race/ethnicity data is missing
NY Gov. Cuomo expands vaccine eligibility in New York to include restaurant workers
The Congressional Budget Office predicted that the U.S. economy will return to its pre-pandemic size by middle of 2021
Face mask spat allegedly sparked stabbing, baseball bat attack
Super Bowl bummer: CDC issues COVID guidelines for parties
Taiwan forgives quarantine violation fine imposed on kidnapped man
UK COVID Cops Arrest Man For Handing Out Free Soup
McDonald’s paying employees to get COVID-19 vaccine

B. Numbers & Trends

Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.

Sources: https://www.worldometers.info/coronavirus/ and https://covidtracking.com/

1. Cases & Tests

Worldwide Cases:

Total Cases = 104,384,587
New Cases (7 day average) = 512,366

Observations:

7 day average of new cases has been declining since 1/11
Since 1/11, 7 day average has decreased from 745,708 to 512,366, a decline of 31.3%

US Cases:

Total Cases = 27,027,347
New Cases (7 day average) = 142,512
Percentage of New Global Cases = 27.7%

Observations:

7 day average of new cases has been declining since 1/11
Since, 1/11, the 7 day average has decreased from 254,999 to 142,512, a decline of 42.9%

2. Deaths

Worldwide Deaths:

Total Deaths = 2,262,226
New Deaths (7 day average) = 13,704

Observations:

7 day average of new deaths has been declining since 1/26
Since 1/26, the 7 day average has decreased from 14,401 to 13,704, a decline of approx. 5%

US Deaths:

Total Deaths = 457,856
New Deaths (7 day average) = 3,177
Percentage of Global New Deaths = 23.2%

Observations:

7 day average of new deaths has been declining since 1/26
Since 1/26, the 7 day average has decreased from 3,439 to 3,177, a decline of approx. 7.6%

3. Top 5 States in Cases, Deaths, Hospitalizations, ICU Patients & Positivity (2/2)

https://lh5.googleusercontent.com/gze44kLW4cVwcRNUIWcx7lGrLTOoAFcUmQK1UzaE8-qd3rpTy-BsYmXqgJ46FnPlaGwx2dId0hE9fHZoH0akhxN1js_PbB3q3m2fQ9DJjgUVa6yjb6YKr8B9LNagnZO-JCqPr6V9

https://lh6.googleusercontent.com/sqFXBsXqU7DMeyQ1Z-Y3304kMzT2PXgozsvKmWHBaBPVbfSct-K38B1hKKtaeGANeAXM5DY6Q92EQjbs_p6yqXxeMNRw-YwuBst78B44JEbcqZ1kKNNWNJTVVB81JjTJZGNG75oC

Observations

Positivity trends continue to improve. Nineteen states are now below the 5% threshold deemed safe to reopen.
Hospitalizations have fallen 15% during the last week and the number of hospitalized patients fell below 100,000 for the 4th straight day.
ICU patients fell 11% during the last week and reached their lowest level since 11/28/20.

Positivity Trends

The US Positivity Rate fell to 8.0% on 2/2, the lowest level since 11/8/20. Nineteen states are now reporting at or below the 5% threshold determined to safely reopen.

Nine states reported higher positivity rates over the last week (-4 states since 1/26).
PA leads the US with an average of 32.3% of all tests resulting positive
Zero states: 7-day positivity rates greater than 40% (unch since 1/26)
One state (PA): 7-day positivity rates greater than 30% (-6 since 1/26)
Six states (IA, ID, KS, AL, KY, SD: 7-day positivity rates greater than 20% (-10 since 1/26)
Nineteen states: 7-day positivity rates less than 5% (+15 since 1/26)
In total, 31 states have 7-day positivity rates greater than 5% (-15 since 1/26)

Hospitalization Trends

Hospitalizations declined 14.8% last week to 92,880 patients. This represents the lowest level since 11/28/20 and the 4th straight day of fewer than 100,000 patients.

Zero states had increases of hospitalized patients of more than 10% in the past week (-3 since 1/26). Only VT saw an increase in patients (+1).
24 states have more than 1,000 hospitalized patients (-3 since 1/26).
49 states saw decreases in the number of hospitalized patients over the past week. (+3 since 1/26).

Patients in ICU Trends

The number of patients in the ICU declined 10.6% last week to 18,388 patients. This represents the lowest level since 11/28/20.

Four states (VT, WA, IA, MS) have seen an increase in the number of ICU patients since a week ago (-2 since 1/26).
26 states have more than 100 patients in ICU, (-2 since 1/26).
45 states saw decreases in the number of ICU patients over the past week (+16 since 1/19).

4. Latest Covid Surge Appears to Flame Out Even in Worst Hot Spots

Even in the most devastated U.S. counties, the latest C19 surge is receding, buying authorities time as they attempt to vaccinate about 330 million people.
Recent hot spots including Webb County, Texas; Maricopa County, Arizona; and Greenville and Spartanburg counties in South Carolina have seen cases trend downward in the past week, according to USAFacts, a nonprofit statistics aggregator used by the U.S. Centers for Disease Control and Prevention.
Among the top-five hot spots with populations of at least 250,000, only Pinal County, Arizona, saw cases increase.

The data is another sign of relief for the U.S. health-care system. The U.S. has been administering an average of 1.26 million doses of C19 vaccine per day in the past week, but just about 1.4% of the population has received the required two doses, according to the Bloomberg Virus Tracker. At the same time, the progress could be threatened by new Covid variants and the community’s inclination to prematurely ease up on safety practices.
The U.S. posted 165,985 new C19 cases on Thursday, dropping the seven-day average to 162,157, the lowest since Dec. 1, according to Johns Hopkins University data.
Deaths, a lagging indicator, remain high: The U.S. added 3,895 to the toll on Thursday, and the total is nearly 434,000, including Friday’s partial count from Johns Hopkins.
According to Covid Tracking Project data:
- The number of people hospitalized with C19 in Vermont rose 24% to 62 in the past week, making it the only state to see an increase.
- Arizona still has the most people hospitalized per capita, but the numbers are falling.
- The seven-day average of deaths, which lag cases by weeks, hit records in the U.S. Census Bureau’s South and West regions. It has been falling in the Northeast and Midwest.

Source: https://www.bloomberg.com/news/articles/2021-01-29/latest-covid-surge-appears-to-flame-out-even-in-worst-hot-spots

5. US Vaccinations

The US CDC reported 49.94 million vaccine doses distributed and 32.22 million doses administered. The US has administered 64.5% of the distributed doses, which is an increase of more than 10 percentage points from Friday’s update (54.1%). In total, 26.02 million people (approximately 7.9% of the US population) have received at least 1 dose of the vaccine, and 5.93 million (1.8%) have received both doses. The US is now averaging 1.36 million doses administered per day, a 20% increase from the previous week. The breakdown of doses by manufacturer remains relatively even, with slightly more Pfizer/BioNTech doses administered (17.36 million; 54%) than Moderna (14.76 million; 46%).
The CDC moved data for vaccination at long-term care facilities (LTCF) to its own dashboard. A total of 3.75 million doses have been administered through the Federal Pharmacy Partnership for Long-term Care Program*, covering 3.14 million individuals with at least 1 dose and 594,857 with 2 doses. The dashboard breaks down the doses by those administered to LTCF residents and those administered to staff. Based on the available data, approximately 60% of the doses have gone to residents and 40% to staff.

Source: Johns Hopkins COVID-19 Update

C. New Variants (Mutations) of Coronavirus

1. Emerging Variants

As scientists continue to monitor emerging coronavirus (SARS-CoV-2) variants of concern (VOCs), researchers are identifying new mutations.
Of particular concern is the E484K mutation, which consists of an amino acid change in the spike receptor binding domain of the SARS-CoV-2 virus. This change appears to result in increased binding strength of the spike protein to the ACE2 receptor, which is how the virus enters human cells. Notably, the E484K mutation appears to result in increased transmissibility and resistance to monoclonal antibody treatments. This mutation has been identified in several variants of SARS-CoV-2 in different geographic areas, including Brazil and the UK, and it appears to be increasing in prevalence, which suggests increased fitness compared to other mutations. The fact that this mutation has been independently acquired in multiple locations and variants indicates that the E484K changes in the spike gene are broadly advantageous to SARS-CoV-2 and may continue to arise in subsequent variants.
Aside from the E484K mutation, scientists monitoring the B.1.1.7 VOC also must track its prevalence and incidence among the population. Since whole genome sequencing to detect the Δ69-70 mutation is costly and time consuming, the UK’s NERVTAG expert group used existing laboratory PCR-based testing to track the variant. Specifically, the Δ69-70 mutation in the spike gene causes S gene target failure (SGTF) in the ThermoFisher TaqPath assay, resulting in a false negative PCR test from a known positive sample. By looking for SGTF in known positive samples (confirmed by other PCR assays), researchers can monitor the extent of the Δ69-70 mutation in the B.1.1.7 VOC without the need for time- and resource-intensive whole genome sequencing methods.

Source: Johns Hopkins COVID-19 Update

2. Coronavirus Mutations Are Taking Over

Since it was first detected in China in 2019, the new coronavirus—like all viruses—has undergone changes to the underlying code that determines its structure and behavior. Many of these genetic mutations have little impact on the virus’s ability to infect humans or spread through populations. But others, like those seen in recent variants found in the U.K., Brazil and South Africa, can produce a more transmissible pathogen, as surging infections in those places suggest.
The more people the virus infects, the more chances it has to evolve, according to Theodora Hatziioannou, a Rockefeller University virologist who is studying the new variants.
Since the start of the pandemic, scientists using coronavirus (SARS-CoV-2) samples collected around the globe have been cataloging these genetic mutations. This has allowed them to build a family tree charting how the virus is evolving.
Here are some milestones in evolution of the C19-causing virus and how tweaks to its genetic code led to the new, potentially more infectious strains that are making their way around the world:

Decisive Mutation

Early last year, scientists detected a mutation in Europe that makes the virus more transmissible than the original versions detected in China.
The mutation, called D614G, alters the shape of spike proteins on the surface of the virus, making it more efficient at binding to and infecting cells.
Variants with the D614G mutation quickly overtook earlier versions of the virus.
“By June, it had replaced the ancestral virus,” said Jeremy Luban, a University of Massachusetts Medical School virologist who has studied the mutation. “Everywhere it went, it became the dominant strain.”

Summertime Spread

A new variant, known as 20E (EU1), was first detected in Spain last summer.
It has since spread widely throughout Europe.
20E (EU1) doesn’t appear to have mutations that make it more transmissible than early variants. Rather, it may have just been in the right place at the right time–a popular European holiday destination at the height of summer. “It could be summertime travel, it could be because you got rid of all your restrictions or it could be because it’s more transmissible,” said Emma Hodcroft, an epidemiologist at the University of Bern in Switzerland, who led a study on the variant.

The New Variants

The variants detected recently in the U.K. and South Africa have several novel changes in their spike-protein genes.
Scientists think one mutation these variants share could help the virus attach to and enter cells. The recently detected variant from Brazil shares a key spike-protein mutation with the one from South Africa.
“What we’re seeing is exactly what we expect to see. The surface proteins of the virus are under tremendous pressure to change,” said Sean Whelan, a virologist at Washington University in St. Louis. “All the virus really cares about is multiplying…If it can get into the cells of the [host] and avoid the immune system of that host, it will multiply. Whether it causes disease is a different question.”
Some scientists worry the variant from South Africa could be better at evading antibodies produced in response to natural infection and vaccination.
Preliminary estimates suggest the variant from the U.K. is 50%–70% more transmissible than earlier versions of the virus. And U.K. scientists said recently that early data suggested it could also be deadlier.
The variants found in the U.K. and South Africa have become the dominant types in countries where they were first detected.
The variant from the U.K. has spread widely abroad. As of late January, it had been reported in 70 countries and territories. The variant from South Africa has been reported in more than 30.

https://si.wsj.net/public/resources/images/B3-HQ241_UKGlob_700PX_20210129191514.jpg

Countries and territories where the variant from the U.K. has been reported

The variant from the U.K. had been detected in more than two dozen U.S. states through late January.

https://si.wsj.net/public/resources/images/B3-HQ246_USMAP__700PX_20210129204249.jpg

U.S. states where the variant from the U.K. has been detected

The Centers for Disease Control and Prevention projected it could become the dominant domestic strain by mid- to late March unless steps are taken to slow it. The variants first found in South Africa and Brazil have also been detected in the U.S.
The full extent of their spread is difficult to gauge. Aside from the U.K. and Denmark, few countries with active outbreaks have done extensive genetic sequencing of the virus, said Dr. Hodcroft.
“At the moment, almost the rest of the world is a blind spot.”

Source: https://www.wsj.com/articles/how-coronavirus-mutations-are-taking-over-11612019829?mod=searchresults_pos1&page=1

3. Coronavirus variants: What they do and how worried you should be

Scientists around the world have been closely tracking mutations and variants since the pandemic began, watching some rise and fall without much ado. But in recent months, they have become disquieted by at least three variants. These variants of concern, or VOCs, have raised critical questions—and alarm—over whether they can spread more easily than previous viral varieties, whether they can evade therapies and vaccines, or even whether they’re deadlier.
With much research yet to be done, there are a lot of unanswered questions. But researchers are working quickly to address the most important unknowns. High on the list is whether the vaccines we already have will be effective against the variants. So far, it seems likely that they will be. Still, the virus is sending a clear message: with rampant transmission accelerating viral evolution, more variants will arise and we need to be prepared.

Variant Origin	UK Variant	South African	Brazil
Variant	B.1.1.7	501Y.V2	P.1
Alternative Names	501Y.V1 and VOC 202012/01	B.1.351	501Y.V3
Number of Countries Reporting cases	70	31	8
Increased transmissibility	Yes	Suggested, but not determined	Suggested, but not determined
Increased Severity and Mortality	A “Realistic Possibility”	Not determined	Not determined
Vaccine Efficacy	Still effective	Still protective, but efficacy reduced. J&J results showed a 52% efficacy.	Not determined
First reported cases	September 2020	October 2020	December 2020
Transmission	People infected with B.1.1.7 will go on to infect an additional 0.36 to 0.68 people on top of how many they would have infected if they were carrying an earlier version of the virus. More recent estimates have been roughly in this range, suggesting B.1.1.7 has around a 47 percent or 56 percent increase in transmission.	There is clear concern that 501Y.V2 is spreading more easily than past versions of the virus. Preliminary studies also suggested that the variant was linked to higher viral loads—that is, higher relative levels of virus genetic material detected in people’s respiratory tracts via diagnostic PCR tests	By late December, 42 percent of SARS-CoV-2 specimens sequenced in Manaus were of the P.1 lineage.
US Impact	A modeling study published by the US Centers for Disease Control and Prevention on January 15 estimated that it will become the predominant strain in the US in March.	On January 28, the CDC released a statement saying it was aware of the country’s first cases of 501Y.V2, detected in South Carolina. “CDC is early in its efforts to understand this variant and will continue to provide updates as we learn more,” the agency said in a statement.	It has now been detected in the United States, but it’s early.
Mutations	Lab experiments have suggested that changing from an N to a Y at 501 increases the spike’s ability to bind ACE2, and experiments in mice linked the mutation to increased infectiousness and disease.	Two notable mutations in spike’s RBD make experts nervous: K417N and E484K. The E484K mutation is the most worrisome.Studies indicate that spike proteins with a 484 mutation were pitted against the antibody-loaded blood from 35 people who had recovered from a SARS-CoV-2 infection, virus neutralization often—but not always—dropped significantly. In some cases, E484K reduced neutralization tenfold.	With the spread in Manaus, researchers immediately became concerned that P.1 has increased transmissibility and/or is able to escape immune responses in people who have recovered from COVID-19. For now, firm data on both of these points is lacking. In particular, there are 10 mutations in the spike, including some usual suspects: N501Y, E484K, and K417T.
Disease severity/mortality	On January 21, a UK government advisory group—NERVTAG—found preliminary evidence that “there is a realistic possibility that infection with VOC B.1.1.7 is associated with an increased risk of death compared to infection with non-VOC viruses.”	No evidence that 501Y.V2 causes more severe disease or more deaths.	So far, there is no evidence that P.1 causes more severe disease or more deaths.

Source: https://arstechnica.com/science/2021/01/coronavirus-variants-what-they-do-and-how-worried-you-should-be/

4. U.K. Variant Probed for Increased Risk to Younger People

Doctors began noticing the change in December as the U.K.’s new coronavirus variant spread. In hospital critical-care units, they were seeing more younger people and women with serious cases of C19, a disease that has inflicted its worst symptoms largely on older patients and men.
The shift—backed up now by statistical studies—is part of an urgent puzzle preoccupying British public-health officials as they race to understand a strain of the virus that is more transmissible and, some studies indicate, could be deadlier than earlier versions.
One early hypothesis, scientists say, is that one of the virus’s genetic mutations makes it better at invading a greater number of cells inside the body, leading to serious sickness in people who with previous C19 variants would only have had mild or no symptoms.
David Strain, a physician and instructor at the University of Exeter’s medical school who is also treating C19 patients, said initial research paints a picture of a virus variant that is like a burglar that has become better at breaking and entering—into vulnerable cells in this case, not houses.
“We think that’s why it’s making people sicker as well as being more transmissible,” Dr. Strain said.
Virologists suspect that it is a particular mutation known as N501Y on the new variant’s spike protein that has enhanced its ability to enter and infect human cells and to move more efficiently through the human body.
Some things, doctors and scientists say, don’t seem to have changed with the new variant. Once hospitalized, patients seem to have the same chance of survival as before and doctors can’t tell from symptoms which variant a patient has.
In London, the southeast and east of England, where the new variant was first identified in a test sample from Sept. 20, the mean age of patients admitted to intensive-care units fell to 58.9 years from Dec. 1 to Jan. 21 from 61.4 years between September and the end of November.
The proportion of women admitted into ICUs rose to 35.1% from 30.1% in the same period. Data from the rest of the country show a similar pattern.
Through December, the proportion of 18- to 54-year-olds admitted to English hospitals with C19 also began to trend up, before a national lockdown was imposed on Jan. 4.
Not all doctors are convinced this is explained by mutations in the new variant. Some think it could also be a matter of behavior changes, with more people, especially younger ones, mixing during the holiday season and becoming infected.
Luke Allen, a local doctor in Oxford, for instance, said he has been treating more younger patients but that he is seeing more C19 patients in general, and the ratio of people seems to be the same as in the first peak.
He attributes the increased numbers to the greater transmissibility of the new variant and increased socializing over the holidays. “That increases the chances of their contact with us,” Dr. Allen said.
There is still considerable debate around whether the new variant is in fact deadlier, as some research suggests.
The new variant, which has become the dominant version across the U.K., is estimated to be 30% to 70% more infectious than earlier varieties. Last week, a government health advisory panel said studies suggest there was a realistic possibility that it also could be 30% to 40% deadlier than the previous variant.
Julian Tang, a clinical virologist and professor of respiratory medicine at the University of Leicester, said more evidence was needed to prove that the new variant was deadlier, given that social mixing was allowed during the winter months, greatly accelerating hospitalization rates.
“Viruses generally mutate to be more transmissible and less lethal,” he said.
The disease caused by the variant so far doesn’t appear any different from that provoked by its ancestors, but because the virus itself is able to move around a patient’s system more easily, it can outpace the body’s immune response, doctors suspect.
“If you are getting much stronger binding you may need a lower infectious dose to become infected, which would increase the risk of transmission,” Dr. Horby said. “Then, if it’s been able to spread between cells much quicker within the lungs, then that may increase the rate of disease and the rate of inflammation which may then progress quicker than your body can respond to.”

Source: https://www.wsj.com/articles/coronavirus-variant-in-u-k-probed-for-increased-risk-to-younger-people-11611661304

5. South Carolina sees first US cases of South Africa C19 variant

Health authorities have identified the first U.S. cases of C19 caused by a fast-spreading form of the coronavirus initially seen in South Africa, in two people in South Carolina.
Neither person has a history of travel to countries where the variant has been confirmed, and there is no connection between the two people, South Carolina health officials said Thursday. That indicates there has been some local spread of the variant after it arrived in the United States. One case was found in South Carolina’s Pee Dee region, and one in the Lowcountry.
The announcement Thursday means that three coronavirus variants that appear to be more contagious and have emerged in recent months have all been documented in the United States. But in a way, the news was no surprise to experts. They had for weeks said the variant that first cropped up in South Africa, called B.1.351, was likely already in the U.S., but this country’s limited system of surveillance for different iterations of the coronavirus meant the variant likely went unnoticed once it was imported via a traveler and could have even been spreading.

Source: https://www.statnews.com/2021/01/28/south-carolina-first-cases-of-south-africa-variant/

6. Redesigning COVID vaccines to protect against variants

As evidence grows that new variants of the coronavirus (SARS-CoV-2) can evade immunity produced by vaccines or previous infections, scientists are exploring the idea of redesigning the vaccines currently being rolled out worldwide.
Researchers are still debating whether the new variants could undercut the effectiveness of these first-generation C19 vaccines. But some vaccine developers are charging forward with plans to update their shots so that they could better target the emerging variants, such as those identified in South Africa and Brazil. These lineages carry mutations that seem to dampen the effects of antibodies crucial to fending off infection. Researchers are also considering the possibility that vaccines against the coronavirus might have to be updated periodically, as they are for influenza.

Fast-spreading COVID variant can elude immune responses

The best and most immediate way to combat the threat of emerging variants is still probably to quickly vaccinate as many people as possible with current shots, says Mani Foroohar, a biotechnology analyst at the investment bank SVB Leerink in Boston, Massachusetts: “We need to get vaccines in arms and to smother this virus before it blows up in our face again.”
But Foroohar and others expect that, in the future, a bevy of new vaccines will emerge to tackle the C19 variants head on. Nature explores the open questions about updating the world’s coronavirus vaccines.

Will we need updated C19 vaccines?

“I think it’s starting to look that way,” says Kanta Subbarao, a virologist at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia.
Laboratories worldwide are racing to understand the threat that emerging coronavirus variants pose for vaccines. But early insights from these studies are mixed and incomplete. A variant identified in late 2020 in South Africa, called 501Y.V2 (also known as variant B.1.351), is among the most worrying. Lab assays have found that it carries mutations that sap the potency of virus-inactivating ‘neutralizing antibodies’ that were made by people who received either the Pfizer or Moderna RNA vaccines.
Whether these changes are enough to lower the effectiveness of those vaccines is not clear, says Subbarao. “That is the million-dollar question, because we don’t know how much antibody you need.” Other immune responses that vaccines prompt might help to protect against the effects of variants.
But on 28 January, biotech firm Novavax released data from clinical trials showing that its experimental vaccine, designed to combat the original virus, was about 85% effective against a variant identified in the United Kingdom — but less than 50% effective against 501Y.V2. That drop is concerning, say researchers, because it indicates that 501Y.V2 and other variants like it can cause a significant drop in vaccines’ effectiveness.
“I think it’s inevitable for the vaccines to maintain tip-top efficacy, they will need to be updated. The only question is how often and when,” says Paul Bieniasz, a virologist at the Rockefeller University in New York City who co-led one of the neutralizing-antibody studies.

How should we decide when to update vaccines?

Scientists, health officials and vaccine makers are starting to hash this out. Researchers are only beginning to learn how different mutations alter vaccine responses and how evolutionary forces can cause mutations to spread. “I certainly wouldn’t update them now,” says Bieniasz.
One model that C19 vaccine updates could follow is that of seasonal flu vaccines, says Subbarao, who directs the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne. Centres, including hers, monitor emerging flu strains for genetic changes that might influence vaccines’ effectiveness. Researchers use studies with ferret and human antibodies to determine whether a new flu strain is likely to evade a previous season’s vaccine, and therefore necessitate an update. These reviews are conducted annually for each hemisphere’s flu season, and changes are made only when a vaccine-evading strain is widespread, says Subbarao. “If it’s localized to one region, one country, we wouldn’t change the vaccine for the whole hemisphere.”
Generally, the threshold for updating flu vaccines is similar in magnitude to the threshold for changes in neutralizing-antibody responses that researchers have linked to the 501Y.V2 variant. But it is not yet clear how these shifts — and the geographical distribution of different variants and mutations — will inform C19 vaccine updates. “Those discussions are just beginning,” says Subbarao. “We can’t be chasing every variant that emerges.”

How will the vaccines be updated?

That’s another open question. Some C19 vaccines, including the major ones made by Moderna, Pfizer and AstraZeneca, instruct cells to produce the virus’s spike protein — the immune system’s key target for coronaviruses. Variants including 501Y.V2 carry spike mutations that alter regions targeted by neutralizing antibodies.
One possibility is to swap vaccines’ old versions of the spike protein — based largely on the virus that was first identified in Wuhan, China — for an updated molecule that has the specific amino-acid changes that hinder antibody responses. But researchers will first need to determine whether any such changes have knock-on effects that alter how the immune system reacts to the vaccine. Another possibility is to include both new and old forms of the spike protein in a single jab — scientists call this a multivalent vaccine.
Moderna has started work on updating its mRNA vaccine to match spike mutations in 501Y.V2. The biotech company, based in Cambridge, Massachusetts, says it also intends to test the effectiveness of a third dose of its original coronavirus vaccine, and is looking into the possibility of a multivalent vaccine, said Tal Zaks, Moderna’s chief scientific officer, in a 25 January call with investors. But before deciding on any path, researchers will need to study how animals, and probably humans, respond to any potential vaccine update, says Subbarao.“It’s not going to be as simple as [altering] an amino acid site and saying ‘okay we got it’.”

How will vaccines be trialled and approved?

Vaccine developers tested the currently available C19 vaccines in phase III trials involving tens of thousands of participants before regulators authorized the drugs’ use. But that kind of testing for a revamped vaccine would be slow and difficult now that the first-generation vaccines are being deployed worldwide, says immunologist Drew Weissman at the University of Pennsylvania in Philadelphia: “I can’t imagine how they could do a phase III trial for a variant.”
It’s unclear how much clinical data would be needed to approve a C19 vaccine update. New seasonal flu vaccines typically do not require fresh trials. But regulators do not have the assurance of decades of experience and clinical data with C19 vaccines. “They might say, ‛It’s a brand new vaccine, let’s do a couple of clinical trials,’” says Weissman.
The size and duration of those trials could depend on whether researchers can find ‛correlates of protection’: measurable features of an immune response, such as a particular level of neutralizing antibodies, that can provide a marker for protection against C19. With such markers, researchers would not need to wait for trial participants to become infected with coronavirus to know whether the vaccines are working — they could simply measure immune responses after each dose.
There is no guarantee that a robust correlate will emerge, says Paul Offit, a vaccine researcher at the Children’s Hospital of Philadelphia in Pennsylvania. But even without a definitive correlate, researchers might still be able to demonstrate that their new vaccine produces antibody levels similar to the first-generation vaccines. Moderna has said that it expects to be able to rely on clinical trials involving hundreds, rather than thousands, of participants to push forward with its vaccine against the 501Y.V2 variant. Foroohar expects that it will take the company about five months to go from producing the new vaccine to submitting data from its trials to regulators.

How will people respond to updated vaccines if they’ve already been immunized?

Researchers don’t yet know how a person who has been fully vaccinated with a first-generation C19 vaccine will respond to a fresh vaccine against a new variant. Immunologists have long observed that people tend to mount more robust immune responses to the first variant of a pathogen that they encounter than subsequent variants. This phenomenon could mean that updated vaccines might trigger more muted immune responses than those to a first vaccine. “The fear is that boosting somebody with a variant won’t make a new response against that variant,” says Weissman. “It’ll just boost the old response.”
But Weissman argues that there is some evidence that RNA vaccines may not fall prey to this trend. For reasons that are not clear, some RNA vaccines trigger surprisingly complex immune responses, yielding antibodies that target regions of viral proteins that are often not detected in responses to other kinds of vaccines. This could mean that RNA vaccines will also be better able to target the changes present in a variant, Weissman says.
And Offit notes that a variant-specific response may not be necessary: even if an updated vaccine mainly boosts the response to an earlier coronavirus vaccine, that may still be enough to fend off the variants, he says.

What are vaccine makers doing?

Like Moderna, other coronavirus vaccine makers have said that they are looking into updating their vaccines. They include Johnson & Johnson of New Brunswick, New Jersey, which is developing a single-shot coronavirus vaccine.
Some aspiring vaccine makers have had their eye on the threat that escape variants might pose from the start. A team at Gritstone Oncology decided to focus on this potential problem by designing a vaccine that targets multiple sites on several viral proteins, in contrast to first-generation shots that target only the spike protein, says Andrew Allen, president of the company in Emeryville, California. The hope is that the vaccine, which should soon start clinical trials, will make it difficult for the virus to evade immunity because many genetic changes would be necessary for it to do so. “You can either play whack-a-mole and chase the variants, or you can try to get ahead of them,” Allen says.
Because updating the construction of exisiting vaccines is relatively simple, a new RNA vaccine could be designed and manufactured for clinical testing within six weeks, Weissman estimates.
But that is only the beginning. “Mass-producing a vaccine is hard. To start all over again will be hard,” says Offit.
Some researchers are expecting periodic updates to coronavirus vaccines, as with flu, to become a way of life. “This is not unusual,” says Stanley Plotkin, a consultant who advises companies on vaccines. But it could mean that worries over supply chains and logistics will continue for some time.

Source: https://www.nature.com/articles/d41586-021-00241-6

D. New Scientific Findings & Research

1. Melatonin Produced in the Lungs Prevents C19 Infection

Melatonin synthesized in the lungs acts as a barrier against the coronavirus (SARS-CoV-2), preventing expression of genes that encode proteins in cells such as resident macrophages in the nose and pulmonary alveoli, and epithelial cells lining the alveoli, all of which are entry points for the virus. The hormone, therefore, prevents infection of these cells by the virus and inhibits the immune response so that the virus remains in the respiratory tract for a few days, eventually leaving to find another host.
The discovery by researchers at the University of São Paulo (USP), in Brazil, helps understand why some people are not infected or do not manifest symptoms of C19 even when reliably diagnosed as carriers of the virus by RT-PCR. In addition, it offers the prospect of nasal administration of melatonin, in drops or as a spray, to prevent disease from developing in pre-symptomatic patients.
Pre-clinical and clinical trials will be needed to prove the therapeutic efficacy of melatonin against the virus, the researchers stress in an article on the study published in the journal Melatonin Research.
The study was supported by FAPESP.
“We showed that melatonin produced in the lung acts as a barrier against SARS-CoV-2, preventing the virus from entering the epithelium, activating the immune system and triggering the production of antibodies,” Regina Pekelmann Markus, a professor at USP’s Institute of Biosciences (IB) and principal investigator for the project, told Agência FAPESP.
“This action mechanism by pulmonary melatonin must also involve other respiratory viruses such as influenza,” she added.
Markus began researching melatonin in the 1990s. In a study involving rodents, she showed that the hormone, produced at night by the pineal gland in the brain to tell the organism daylight has gone and it should prepare for sleep, can be produced in other organs, such as the lungs.
In a study also involving rodents, published in early 2020 in the Journal of Pineal Research, Markus and collaborators showed that resident macrophages in the pulmonary airspace absorb (phagocytize) particles of pollution. This aggressive stimulus induced the production of melatonin and other molecules by the macrophages, engulfing the particulate matter in the air breathed in by the animals and stimulating mucous formation, coughing, and expectoration to expel the particles from the respiratory tract.
When they blocked melatonin synthesis by resident macrophages, the researchers observed that the particles entered the bloodstream and spread throughout the organism, even invading the brain.
Based on the finding that melatonin produced in the lungs altered the entry points for particulate matter from air pollution, Markus and collaborators decided to investigate whether the hormone performed the same function with regard to SARS-CoV-2. “If so, the virus wouldn’t be able to bind to the ACE-2 receptor on cells, enter the epithelium and infect the organism,” Markus said.
“We found that when MEL-Index was high the entry points for the virus in the lungs were closed, and when it was low these ‘doors’ were open. When the doors are shut, the virus wanders around for a time in the pulmonary airspace and then tries to escape in search of another host,” Markus said.
Because lung melatonin inhibits transcription of these genes that encode proteins for viral entry point cells, application of melatonin directly into the lungs in the form of drops or spray could block the virus. More research is required to prove that this is indeed the case, however, the researchers note.
Another idea could be to use MEL-Index, the pulmonary melatonin metric, as a prognostic biomarker to detect asymptomatic carriers of SARS-CoV-2.

Source: https://scitechdaily.com/melatonin-produced-in-the-lungs-prevents-covid-19-infection/

2. Heparin reduces infection

An international team of researchers led by the Universities of Liverpool and Keele, working with Public Health England, has found that the common anticoagulant drug heparin inhibits the coronavirus (SARS-Cov2) spike protein, by reducing the virus’ ability to attach to human cells and infect them.
The research, published in the journals British Journal of Pharmacology, and Thrombosis and Haemostasis, found that heparin interacts with the spike protein on the surface of coronavirus (SARS-CoV2), destabilizing its structure and preventing it from docking with the ACE2 receptor on human cells.
Molecular modelling by collaborators at Queensland University in Australia showed how heparin can stick to the surface of the spike protein to achieve these effects, and studies with live SARS-CoV2 virus carried out at Public Health England’s Porton Down laboratory showed that unfractionated heparin (but not low molecular weight heparins) could inhibit cell infectivity at doses similar to those currently used in clinical settings as an anticoagulant.
Crucially, the data strongly supported the clinical testing of inhaled (“nebulised”) unfractionated heparin, since the doses known to be delivered to the lungs would have very strong anti-viral effects.
Professor Jeremy Turnbull from the Department of Biochemistry and Systems Biology at the University of Liverpool said: “This is exciting news since heparin could be rapidly repurposed to help alleviate C19 infections, or possibly as a prophylactic treatment for high-risk groups such as medical staff or care workers. The results have also led us to investigate other novel compounds which mimic heparin that could potentially be effective against SARS-CoV2.”
Dr Mark Skidmore from the School of Life Sciences at Keele University co-led the research. He said: “We also know that heparins inhibit a range of other viruses, so studying these drugs could provide new therapeutic strategies, and possibly a first-line of defense against emerging viral threats in the future, for example while vaccines are developed.”
The early release of preprint data from this study in March 2020, now published in peer-reviewed journals, has stimulated international efforts to explore the use of heparins for C19 treatment. Further work is now ongoing to explore the potential of heparin and heparin-mimicking compounds as potential broad-spectrum antiviral drugs for C19 and other emerging viral threats.

Source: https://www.eurekalert.org/pub_releases/2021-01/uol-htc012821.php

3. C19 rarely spreads through surfaces. So why are we still deep cleaning?

When Emanuel Goldman went to his local New Jersey supermarket last March, he didn’t take any chances. Reports of C19 cases were popping up across the United States, so he donned gloves to avoid contaminated surfaces and wore a mask to prevent him inhaling tiny virus-laden droplets from fellow shoppers. Neither gloves nor masks were recommended at the time.
Then, at the end of March, a laboratory study showed that the coronavirus (SARS-CoV-2) can persist on plastic and stainless steel for days. That triggered startling headlines and a slew of advice on how to decontaminate everything from doorknobs to groceries. It also seemed to confirm guidance issued by the World Health Organization (WHO) in February that the virus that causes C19 can spread through contaminated surfaces, known as fomites.
By May, the WHO and health agencies around the world were recommending that people in ordinary community settings — houses, buses, churches, schools and shops — should clean and disinfect surfaces, especially those that are frequently touched. Disinfectant factories worked around the clock to keep up with heavy demand.
But Goldman, a microbiologist at Rutgers New Jersey Medical School in Newark, decided to take a closer look at the evidence around fomites. What he found was that there was little to support the idea that SARS-CoV-2 passes from one person to another through contaminated surfaces. He wrote a pointed commentary for The Lancet Infectious Diseases in July, arguing that surfaces presented relatively little risk of transmitting the virus. His conviction has only strengthened since then, and Goldman has long since abandoned the gloves.
Many others reached similar conclusions. In fact, the US Centers for Disease Control and Prevention (CDC) clarified its guidance about surface transmission in May, stating that this route is “not thought to be the main way the virus spreads”. It now states that transmission through surfaces is “not thought to be a common way that C19 spreads”.
As evidence has accumulated over the course of the pandemic, scientific understanding about the virus has changed. Studies and investigations of outbreaks all point to the majority of transmissions occurring as a result of infected people spewing out large droplets and small particles called aerosols when they cough, talk or breathe. These can be directly inhaled by people close by. Surface transmission, although possible, is not thought to be a significant risk.
But it’s easier to clean surfaces than improve ventilation — especially in the winter — and consumers have come to expect disinfection protocols. That means that governments, companies and individuals continue to invest vast amounts of time and money in deep-cleaning efforts. By the end of 2020, global sales of surface disinfectant totalled US$4.5 billion, a jump of more than 30% over the previous year. The New York Metropolitan Transit Authority (MTA), which oversees subways and buses and lost billions of dollars in passenger revenue in 2020, spent $484 million last year in its response to C19, including enhanced cleaning and sanitization, according to a spokesperson.
Part of the problem is that specialists can’t rule out the possibility of fomite transmission, and the guidance from many health agencies about how to deal with surfaces has been unclear as the science has changed. In November, Chinese authorities introduced guidelines requiring disinfection of imported frozen-food packages. And the CDC directs people to a comprehensive list of agents that kill SARS-C0V-2 and says: “Frequent disinfection of surfaces and objects touched by multiple people is important.”
Experts say that it makes sense to recommend hand washing, but some researchers are pushing back against the focus on surfaces. In December, engineer Linsey Marr at Virginia Tech in Blacksburg co-wrote an opinion article for The Washington Post imploring people to ease up on cleaning efforts. “It’s become clear that transmission by inhalation of aerosols — the microscopic droplets — is an important if not dominant mode of transmission,” says Marr, who studies airborne disease transmission. Excessive attention on making surfaces pristine takes up limited time and resources that would be better spent on ventilation or the decontamination of the air that people breathe, she says.

Virus RNA can mislead

The focus on fomites — rather than aerosols — emerged at the very beginning of the coronavirus outbreak because of what people knew about other infectious diseases. In hospitals, pathogens such as methicillin-resistant Staphylococcus aureus, respiratory syncytial virus and norovirus can cling to bed rails or hitch a ride from one person to the next on a doctor’s stethoscope. So as soon as people started falling ill from the coronavirus, researchers began swabbing hospital rooms and quarantine facilities for places the virus could be lurking. And it seemed to be everywhere.
In medical facilities, personal items such as reading glasses and water bottles tested positive for traces of viral RNA — the main way that researchers identify viral contamination. So, too, did bed rails and air vents. In quarantined households, wash basins and showers harbored the RNA, and in restaurants, wooden chopsticks were found to be contaminated. And early studies suggested that contamination could linger for weeks. Seventeen days after the Diamond Princess cruise ship was vacated, scientists found viral RNA on surfaces in cabins of the 712 passengers and crew members who tested positive for C19.
But contamination with viral RNA is not necessarily cause for alarm, says Goldman. “The viral RNA is the equivalent of the corpse of the virus,” he says. “It’s not infectious.”
To address that part of the equation, researchers began testing whether coronavirus samples left for days on various surfaces could infect lab-grown cells. One study in April found that the virus remained infectious on hard surfaces such as plastic and stainless steel for 6 days; on bank notes, it lasted for 3 days; and on surgical masks, at least 7 days. A later study announced that viable virus was present on skin for up to 4 days, but on clothes it survived for less than 8 hours. And others found infectious virus on library books bound in natural and synthetic leather after 8 days.

Unrealistic conditions

Although these types of experiment demonstrate that the coronavirus can survive on surfaces, this doesn’t mean that people are catching it from surfaces such as doorknobs. Goldman and others caution against reading too much into virus-survival studies, because most don’t test conditions that exist outside the lab. “They were experiments that started out with humongous amounts of virus, nothing that you would encounter in the real world,” he says. Other tests have used mock saliva and controlled conditions such as humidity and temperature, all of which widen the gulf between experimental and real-world conditions, says Goldman.
Only a handful of studies have looked for viable virus outside the lab. Tal Brosh-Nissimov, who heads the infectious-diseases unit at the Assuta Ashdod University Hospital in Israel, and his colleagues swabbed personal items and furniture in hospital isolation units and rooms at a quarantine hotel. Half of the samples from two hospitals and more than one-third of samples from the quarantine hotel were positive for viral RNA. But none of the viral material was actually able to infect cells, the researchers reported.
Indeed, researchers have struggled to isolate viable virus from any environmental samples, not just fomites. In the only study that has succeeded, researchers grew virus particles from hospital air samples collected at least 2 meters from a person with C19.
Nevertheless, scientists warn against drawing absolute conclusions. “Just because viability can’t be shown, it doesn’t mean that there wasn’t contagious virus there at some point,” says epidemiologist Ben Cowling at the University of Hong Kong.
Human exposure studies of other pathogens provide additional clues about fomite transmission of respiratory viruses. In 1987, researchers at the University of Wisconsin— Madison put healthy volunteers in a room to play cards with people infected with a common-cold rhinovirus. When the healthy volunteers had their arms restrained to stop them touching their faces and prevent them transferring the virus from contaminated surfaces, half became infected. A similar number of volunteers who were unrestrained also became infected. In a separate experiment, cards and poker chips that had been handled and coughed on by sick volunteers were taken to a separate room, where healthy volunteers were instructed to play poker while rubbing their eyes and noses. The only possible mode of transmission was through the contaminated cards and chips; none became infected. The combination of experiments provided strong evidence that rhinoviruses spread through the air. But such studies are considered unethical for SARS-CoV-2, because it can kill.
Although it’s probably rare, says Cowling, transmission through surfaces can’t be ruled out. “It just doesn’t seem to happen that much, as far as we can tell.”
Estimates of transmission based on levels of viral RNA persisting in the environment seem to bear this out. From April to June, environmental engineer Amy Pickering then at Tufts University in Medford, Massachusetts, and her colleagues took weekly swabs of indoor and outdoor surfaces around a town in Massachusetts. On the basis of the levels of RNA contamination and how often people touched surfaces such as doorknobs and buttons at pedestrian crossings, the team estimated that the risk of infection from touching a contaminated surface is less than 5 in 10,000 — lower than estimates for SARS-CoV-2 infection through aerosols, and lower than surface-transmission risk for influenza or norovirus.
“Fomite (surface) transmission is possible, but it just seems to be rare,” says Pickering, who is now at the University of California, Berkeley. “A lot of things have to fall into place for that transmission to happen.”
That might explain why a global comparison of government interventions to control the pandemic in its early months found that cleaning and disinfection of shared surfaces ranked one of the least effective at reducing transmission. Social distancing and travel restrictions, including lockdowns, worked the best.

Messy data

That leaves researchers sorting through messy epidemiological data about how the virus spreads. Hundreds of studies of C19 transmission have been published since the pandemic began, yet there is thought to be only one that reports transmission through a contaminated surface, by what it termed the snot–oral route. According to the report, a person with C19 in China blew his nose with his hand and then pressed a button in his apartment building elevator. A second resident in the building then touched the same button and flossed with a toothpick immediately after, thereby transferring the virus from button to mouth. But without genome sequences of the viruses infecting each person, transmission through another unknown person couldn’t be ruled out.
In one other case, eight people in China are thought to have been infected after stepping in sewage containing the virus on the street and then walking the contamination into their homes.
Despite the rarity of published examples of fomite transmission, Chinese authorities require that imported frozen food be disinfected. The change in guidelines followed a report, which has not been released in detail, that a worker at a frozen-food business in the northern port city of Tianjin became infected after handling contaminated packaging of frozen pork imported from Germany. But the WHO and other experts have disputed claims that people can be infected through the food chain in this manner.
Cowling says that more detailed investigations are needed, carefully tracking who infects whom, and what surfaces and spaces they shared around the time of infection. “What we really, really value is epidemiological investigations of transmission patterns, whether it’s in households or workplaces or elsewhere,” he says. “I don’t think we’ve been doing enough of that.”

The greatest threat

Armed with a year’s worth of data about coronavirus cases, researchers say one fact is clear. It’s people, not surfaces, that should be the main cause for concern. Evidence from superspreading events, where numerous people are infected at once, usually in a crowded indoor space, clearly point to airborne transmission, says Marr. “You have to make up some really convoluted scenarios in order to explain superspreading events with contaminated surfaces,” she says.
Hand washing is crucial, says Marr, because surface transmission can’t be ruled out. But it’s more important to improve ventilation systems or to install air purifiers than to sterilize surfaces, she says. “If we’ve already paid attention to the air and we have some extra time and resources, then yes, wiping down those high-touch surfaces could be helpful,” she says.
Households can also ease up, says Pickering. Quarantining groceries or disinfecting every surface is going too far. “That’s a lot of work and it also is probably not reducing your exposure that much,” she says. Instead, reasonable hand hygiene, as well as wearing a mask and social distancing to reduce exposure from close contacts is a better place to focus efforts.
The WHO updated its guidance on 20 October, saying that the virus can spread “after infected people sneeze, cough on, or touch surfaces, or objects, such as tables, doorknobs and handrails”. A WHO spokesperson told Nature that “there is limited evidence of transmission through fomites. Nonetheless, fomite transmission is considered a possible mode of transmission, given consistent finding of environmental contamination, with positive identification of SARS-CoV-2 RNA in the vicinity of people infected with SARS-CoV-2.” The WHO adds that “disinfection practices are important to reduce the potential for C19 virus contamination”.
The CDC did not respond to Nature’s queries about inconsistencies in its statements about the risks posed by fomites.
The conundrum facing health authorities, says Marr, is that definitively ruling out surface transmission is hard. Authorities can be reluctant to tell people not to be cautious. “You never want to say, ‘Oh, don’t do that,’ because it can happen. And you know, we should follow the precautionary principle,” she says.
Despite the evolving evidence, the public might have grown to expect extra levels of sanitization after the early months of the pandemic. When the New York MTA surveyed passengers in late September and early October, three-quarters said that cleaning and disinfecting made them feel safe when using transport.
Goldman continues to wear a cloth mask when he leaves home, but when it comes to the possibility of catching the coronavirus from a contaminated surface, he doesn’t take any special precautions. “One of the ways we protect ourselves is by washing our hands,” he says, “and that applies pandemic or no pandemic.”

Source: https://www.nature.com/articles/d41586-021-00251-4

4. C19 Intensive Care Mortality in Sweden Lower Than in Many Other Countries – Here Are the Factors Driving Mortality

New research reveals that the C19 intensive care (ICU) mortality rate in Sweden was lower during the first wave of the pandemic than in many studies from other countries. And while analysis of individual underlying conditions found they were linked to mortality, an analysis looking at all these variables together found C19 mortality in intensive care was not associated with underlying conditions, except for chronic lung disease. This new study did, however, find that, like previous research, mortality was driven by age, severity of C19 disease and the presence and extent of organ failure.
The study is published in the European Journal of Anaesthesiology (the official journal of the European Society of Anaesthesiology and Intensive Care [ESAIC]) and is by Dr. Michelle Chew, Linkoping University Hospital, Linkoping, Sweden, and colleagues.
“Coupled with what is widely perceived to be a ‘relaxed’ national pandemic strategy, results for ICU care in Sweden are understandably under scrutiny,” explain the authors.
They analyzed 1563 adult admissions to Swedish ICUs from March 6 – May 6, 2020 with laboratory confirmed C19 disease, and complete 30-day follow up, and found 30-day all-cause mortality was 27%, while mortality actually within ICU was 23%, indicating the most patients who died after requiring ICU treatment actually died within ICU.
Various factors including age were associated with mortality. Being male raised the risk of death by 50%, while having severe respiratory failure (more advanced disease -present in three quarters of patients) trebled the risk of death. However, except for chronic lung disease (a 50% increased risk of death), the presence of comorbidities was not independently associated with mortality. Also of note was that the degree of hypoxia (insufficient oxygen) was much higher in this Swedish cohort than those from other countries. Put another way, these Swedish patients were generally sicker upon entering ICU.
The ICU mortality of 23% in this Swedish study is between that found in two nationwide studies with small cohorts from Iceland and Denmark, at 15% and 37% respectively. It is lower than the mortality rate reported from a North American study (35%) and a French-Belgian-Swiss study (26-30%). These studies had nearly complete discharge data, meaning that most patients had survived and left ICU or sadly died there, with few patients still being treated at the time of the study.
In one report from Lombardy, Italy, ICU mortality was initially reported to be 26%; however this did not contain complete data as many patients were still being treated. A later study consisting of mostly the same patients and with almost complete ICU follow-up, mortality was 49%. These results are comparable to a recent meta-analysis of 20 studies worldwide (TM Cook and colleagues, Anaesthesia, 2020) that reported an ICU mortality of 42% for patients with completed ICU admissions and discharge data. Another study by Cook and colleagues, being published in Anaesthesia at the same time as this Swedish study (see separate press release) shows global ICU mortality up to October 2020 has since dropped further to 36%.
This new study from Sweden confirms previous findings that mortality rates are significantly higher among those aged 65 years and older. Patients over 80 years of age were seven times more likely to die than those aged 50 years and under, although the authors make clear that their data “demonstrate that provision of intensive care should not be restricted on the basis of age alone”. They add: “Not all over 80 year olds die in ICU, which is one reason why we cannot exclude this group of patients from ICU care based on age alone. All decisions on care must be taken on a patient-by-patient basis”.
As in other studies, a majority of patients suffered from underlying conditions (comorbidities), most commonly high blood pressure, diabetes and obesity. Whilst most comorbidities were associated with death when analyzed separately, their effects were not statistically significant after adjustment for other variables. Severe obesity (BMI>40) was not associated with increased mortality as suggested by other studies. The only underlying condition that was found to have an effect in Swedish patients was chronic lung disease, which was associated with a 50% increased risk of death.
The authors discuss the various aspects of the Swedish ICU policy that could be connected with the lower ICU mortality rate. They say: “We believe that process and organizational factors have likely contributed to the relatively good outcomes seen in Swedish ICUs as staffing, protective equipment, availability of drugs, medical and technical equipment were considered at an early stage at hospital and regional levels.”
In the first quarter of 2020 Sweden had 5.1 ICU beds per 100,000 population, compared to 27/100,000 in the USA. The C19 pandemic unleashed a coordinated response in Swedish ICUs doubling the number of beds from around 500 to more than 1100 at its peak. The proportion of occupied ICU beds in the country during the study period (the peak months of the first wave of the pandemic) never reached maximum capacity. Other factors potentially connected to lower C19 ICU mortality are that anaesthesiology and intensive care are combined specialties in Sweden, and this dual competency enabled rapid diversion of resources from perioperative care to intensive care management.
However, Sweden’s strategy has faced harsh criticism at home and abroad for being too relaxed and dependent on individual responsibility of citizens rather than enforced lockdowns. Sweden’s King also, in late 2020, publicly criticized the country’s C19 strategy as a failure. New laws on public transport and gatherings were enacted in autumn 2020 to limit the rising spread of SARS-CoV-2, and in late 2020, the Swedish Government passed new laws in order to be able to enforce restrictions such as venue closures to prevent cases raging out of control. Future staffing shortages, the looming possibility of burn-out and numerous organizational challenges also remain.
The authors conclude: “Mortality rates in C19 patients admitted to Swedish intensive care units are generally lower than previously reported in other countries despite more severe illness on admission among Swedish patients. Mortality appears to be driven by age, baseline disease severity, and the presence and degree of organ failure, rather than pre-existing comorbidities.”
Professor Chew, who is also the deputy editor-in-chief of the European Journal of Anaesthesiology, adds: “Although Sweden chose a different pandemic strategy to its European neighbors, its population has not been immune to rising infection rates this winter. Only time will tell if the Swedish health care system can sustain the long-term burden of C19 disease.”

Source: https://scitechdaily.com/covid-19-intensive-care-mortality-in-sweden-lower-than-in-many-other-countries-here-are-the-factors-driving-mortality/

5. What does Ebola tell us about C19 immunity?

While the world learns more about C19 each day, new research may hold lessons from an older scourge. Antibody levels in 39 of 51 Ebola survivors’ blood samples surged and dropped nearly a year after recovery. No virus was detected, hinting that it might lurk in their bodies — known Ebola reservoirs are the eyes, central nervous system, and testes — stimulating immune memory of the original infection.
Antibody levels tend to fluctuate, but the later rise causes concern. “Recurrent vaccine boosters in survivors (in addition to heightened surveillance) might be needed,” a related commentary suggests. “The mechanisms of antibody decay have not yet been defined for C19, but recurrent vaccination might be necessary here, too, to achieve durable immunity.”

Source: https://www.nature.com/articles/d41586-020-03044-3

6. Babies develop C19 antibodies from mothers in the womb

Pregnant women who develop C19 antibodies often transfer them to their babies in the womb, a new study shows.
More than 1,400 mothers and newborns were studied, and researchers found antibodies were transferred across the placenta in 72 of 83 infected or previously infected pregnant women, according to the study by the Journal of the American Medical Association’s JAMA Pediatrics published on Friday.
“Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019,” the study says.
Babies born to C19 positive mothers did not develop an infection, and 60 percent of women who had coronavirus antibodies reported no symptoms, according to the researchers.
The finding also recommends expecting mothers should also get vaccinated against other viruses such as influenza so they can protect themselves and their babies. [See article below regarding vaccines and pregnancy]

Source: https://nypost.com/2021/01/30/babies-develop-covid-19-antibodies-from-mothers-in-the-womb/

E. Vaccines & Testing

1. Excellent Vaccine News

The news about the vaccines continues to be excellent — and the public discussion of it continues to be more negative than the facts warrant.
Here’s the key fact: All five vaccines with public results have eliminated C19 deaths. They have also drastically reduced hospitalizations. “They’re all good trial results,” Caitlin Rivers, an epidemiologist at Johns Hopkins University, told me. “It’s great news.”
Many people are instead focusing on relatively minor differences among the vaccine results and wrongly assuming that those differences mean that some vaccines won’t prevent serious illnesses. It’s still too early to be sure, because a few of the vaccine makers have released only a small amount of data. But the available data is very encouraging — including about the vaccines’ effect on the virus’s variants.
“The vaccines are poised to deliver what people so desperately want: an end, however protracted, to this pandemic,” as Julia Marcus of Harvard Medical School recently wrote in The Atlantic.
Why is the public understanding more negative than it should be? Much of the confusion revolves around the meaning of the word “effective.”

What do we care about?

In the official language of research science, a vaccine is typically considered effective only if it prevents people from coming down with any degree of illness. With a disease that’s always or usually horrible, like ebola or rabies, that definition is also the most meaningful one.
But it’s not the most meaningful definition for most coronavirus infections.
Whether you realize it or not, you have almost certainly had a coronavirus. Coronaviruses have been circulating for decades if not centuries, and they’re often mild. The common cold can be a coronavirus. The world isn’t going to eliminate coronaviruses — or this particular coronavirus, known as SARS-CoV-2 — anytime soon.
Yet we don’t need to eliminate it for life to return to normal. We instead need to downgrade it from a deadly pandemic to a normal virus. Once that happens, adults can go back to work, and children back to school. Grandparents can nuzzle their grandchildren, and you can meet your friends at a restaurant.
As Dr. Ashish Jha, the dean of the Brown University School of Public Health, told me this weekend: “I don’t actually care about infections. I care about hospitalizations and deaths and long-term complications.”

The data

By those measures, all five of the vaccines — from Pfizer, Moderna, AstraZeneca, Novavax and Johnson & Johnson — look extremely good. Of the roughly 75,000 people who have received one of the five in a research trial, not a single person has died from Covid, and only a few people appear to have been hospitalized. None have remained hospitalized 28 days after receiving a shot.
To put that in perspective, it helps to think about what Covid has done so far to a representative group of 75,000 American adults: It has killed roughly 150 of them and sent several hundred more to the hospital. The vaccines reduce those numbers to zero and nearly zero, based on the research trials.
Zero isn’t even the most relevant benchmark. A typical U.S. flu season kills between five and 15 out of every 75,000 adults and hospitalizes more than 100 of them.
I assume you would agree that any vaccine that transforms Covid into something much milder than a typical flu deserves to be called effective. But that is not the scientific definition. When you read that the Johnson & Johnson vaccine was 66% effective or that the Novavax vaccine was 89% effective, those numbers are referring to the prevention of all illness. They count mild symptoms as a failure.
“In terms of the severe outcomes, which is what we really care about, the news is fantastic,” Dr. Aaron Richterman, an infectious-disease specialist at the University of Pennsylvania, said.

The variants

What about the highly contagious new virus variants that have emerged in Britain, Brazil and South Africa? The South African variant does appear to make the vaccines less effective at eliminating infections.
Fortunately, there is no evidence yet that it increases deaths among vaccinated people. Two of the five vaccines — from Johnson & Johnson and Novavax — have reported some results from South Africa, and none of the people there who received a vaccine died of Covid. “People are still not getting serious illness. They’re still not dying,” Dr. Rebecca Wurtz of the University of Minnesota School of Public Health told me.
The most likely reason, epidemiologists say, is that the vaccines still provide considerable protection against the variant, albeit not quite as much as against the original version. Some protection appears to be enough to turn this coronavirus into a fairly normal disease in the vast majority of cases.
“This variant is clearly making it a little tougher to get the most vigorous response that you would want to have,” Dr. Francis Collins, director of the National Institutes of Health, said. “But still, for severe disease, it’s looking really good.”

What would an expert do?

The biggest caveat is the possibility that future data will be less heartening. Johnson & Johnson and Novavax, for example, have issued press releases about their data, but no independent group has yet released an analysis. It will also be important to see much more data about how the vaccines interact with the variants.
But don’t confuse uncertainty with bad news. The available vaccine evidence is nearly as positive as it could conceivably be. And our overly negative interpretation of it is causing real problems.
Some people worry that schools cannot reopen even after teachers are vaccinated. Others are left with the mistaken impression that only the two vaccines with the highest official effectiveness rates — from Moderna and Pfizer — are worth getting.
In truth, so long as the data holds up, any of the five vaccines can save your life.
Last week, Dr. William Schaffner of Vanderbilt University told my colleague Denise Grady about a conversation he had with other experts. During it, they imagined that a close relative had to choose between getting the Johnson & Johnson vaccine now or waiting three weeks to get the Moderna or Pfizer vaccine. “All of us said, ‘Get the one tomorrow,’” Schaffner said. “The virus is bad. You’re risking three more weeks of exposure as opposed to getting protection tomorrow.”

Source: New York Times The Morning

2. Should People Who Have Recently Had C19 Be Vaccinated?

A recent report from Public Health England showed that 83% of people who had had COVID were protected from reinfection five months later. Given that 3.7 million people in the UK have had COVID, should those with antibodies be at the back of the vaccine queue?
With the current high death rate, rising case numbers, closed schools and a seemingly interminable lockdown, it is natural to look for ways to speed up the vaccination rollout. Surely those who have already had COVID and recovered can be deprioritized so that people shielding at home can receive the vaccine sooner?
Certainly, the government is not afraid of hacking the process to increase short-term vaccine coverage. The recent example of lengthening the wait for a second doseproves that. But how feasible and effective would it be to not vaccinate people who have had the virus?
First, how sure are we that those people recovered remain protected five months later? While there is no doubt that the antibodies that helped you recover from COVID will last for some time after your illness, hopefully reducing the chance of reinfection, this study was on recovered healthcare professionals, looking at whether they went on to catch COVID again.
Despite the rising case number, a lot improved in those five months, particularly in the availability of protective equipment for healthcare workers and the isolation of COVID patients in hospital. This complicates checking healthcare worker’s antibody-derived protection rates and the calculation for how long you may remain protected.

Antibody Testing

But can’t we just check the antibodies at the test centers, sending those home that don’t need their immune system trained in COVID-focused jiu-jitsu? We can definitely test for antibodies. The test has been available – with a few stop-starts – for some time, but critically it relies on a blood test.
England’s test-and-trace program, which has struggled to process swab tests on the scale needed to match case numbers, would surely collapse at the request to process antibody tests for the entire UK population. Shipping, extraction, processing, testing … all while poor Mrs Jones sits in a school hall with a nurse poised with a vaccine jab waiting for the green light.
How about using the test-and-trace data to sort those that need the jab from those that don’t?
While I will overlook that use of “don’t” (antibodies are not everlasting, even if you have had COVID) the real question here is how much do you trust the accuracy of test and trace, and of people’s ability to self-declare accurately? At the start of the pandemic everyone I spoke with had “had that COVID” despite being untested and unable to identify any exposure other than “I went on a train”.
This improved with mass swab-testing, but accuracy, particularly false positives would be an issue if used to exclude vulnerable people from the vaccine queue.
Like many things related to this pandemic, a good idea is complicated by the detail. Vaccine deployment could be targeted more precisely if we knew how long each of us retained antibodies and had an instant test capable of estimating how much and for how long we would be protected. Given that we have neither – and the NHS is under immense pressure already – the approach of vaccinating in demographic groups currently appears to be our only option.

Source: https://globalbiodefense.com/2021/01/30/should-people-who-have-recently-had-covid-19-be-vaccinated/

3. Racing the virus: Why tweaking vaccines to fight variants won’t be simple

After developing and rolling out C19 vaccines at record speed, drugmakers are already facing variants of the rapidly-evolving coronavirus that may render them ineffective, a challenge that will require months of research and a massive financial investment, according to disease experts.
Executives from Moderna Inc and Pfizer Inc and partner BioNTech SE are considering new versions of their vaccines to respond to the most concerning variants identified so far. That is just one piece of the work needed to stay ahead of the virus, nearly a dozen experts told Reuters.
A global surveillance network to assess emerging variants must be built. Scientists need to establish what level of antibodies will be required to protect people from C19 and determine when vaccines need to be altered. And regulators must convey what is needed to demonstrate updated vaccines are still safe and effective.
“At this point, there is no evidence that these variants have changed the equation in terms of protection from the vaccine,” said Dr. Michael Osterholm, an infectious disease expert at the University of Minnesota. “But we have to be prepared for that.”
Johnson & Johnson told Reuters the concerning variant first identified in South Africa has got its attention and will tweak its vaccine accordingly if needed. Pfizer said it could produce a new vaccine relatively quickly, but a top vaccine executive said manufacturing it presents additional challenges.
Moderna on Monday said lab studies showed antibodies made in response to its vaccine were six times less effective at neutralizing a lab-created version of a South African variant than prior versions of the virus.
A study released on Wednesday ahead of peer review found the South African variant reduced neutralizing antibodies 8.6-fold for the Moderna vaccine and by 6.5-fold for the Pfizer/BioNTech shot, although a separate Pfizer-backed study released on Wednesday suggests its vaccine may be more hardy. Moderna said this week it is starting work on a potential booster shot.

Could Take Months

Just how far protection can drop before a C19 vaccine needs to be altered is not yet known. With influenza, an eightfold drop in vaccine-induced antibody protection means time to update. That does not necessarily apply to this coronavirus.
“The problem is we don’t know what the cut point is for coronavirus,” said Dr. John Mascola, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), whose scientists helped develop Moderna’s vaccine.
Mascola said both studies testing the Moderna vaccine against the South African variant are roughly in the “same ballpark.” It could be that antibody protection is high enough from the vaccine that it will still be effective, he said.
NIAID scientists are analyzing data from Moderna’s late-stage trial to see what level of neutralizing antibodies is required for protection. They are comparing individuals who were vaccinated but got sick anyway to vaccinated people who remained healthy.
It could take two months to complete this work, Mascola said. They hope to produce a benchmark for the minimum level of vaccine-induced antibodies needed to protect against C19.
Companies are waiting for the FDA to relay what testing will be needed for altered vaccines, said Phil Dormitzer, one of Pfizer’s top viral vaccine scientists. With influenza vaccines, companies can make changes without new trials. “But that’s after doing it for 50 years,” he said.
Peter Marks, who oversees the FDA’s vaccine approval process, has said small trials testing updated vaccines in around 400 participants may be needed at first. Even that could add months to the process.
Norman Baylor, chief executive of Biologics Consulting and a former FDA vaccines official, said the agency will lay out the regulatory road. But public health agencies like the U.S. Centers for Disease Control and Prevention and the World Health Organization would decide when vaccines should be updated, as with flu.
Altering Pfizer’s vaccine would require “a very minor change,” Dormitzer said.
Like Moderna’s, it uses messenger RNA (mRNA) technology, which relies on synthetic genes that can be generated and manufactured in weeks.
He estimates the company could make a prototype version in a week or so, and take another two months to scale up and update their lab tests.
J&J, which is expected to release late-stage trial data on its vaccine within days, has laid the groundwork to address troubling virus changes, Chief Scientific Officer Paul Stoffels told Reuters. Its trial included sites in South Africa, which should give the company insight on that variant.
If a change is necessary, Stoffels said J&J likely would add a second strain into its existing vaccine.
“We are looking at this with a lot of attention,” he said.

Source: https://www.reuters.com/article/us-health-coronavirus-vaccines-variant-f/racing-the-virus-why-tweaking-vaccines-to-fight-variants-wont-be-simple-idUSKBN29X1DI

4. Vaccine delivered via skin could help in fight against respiratory diseases

Among infectious diseases that have caused pandemics and epidemics, smallpox stands out as a success story. Smallpox vaccination led to the disease’s eradication in the twentieth century.
Until very recently, smallpox vaccine was delivered using a technique known as skin scarification (s.s.), in which the skin is repeatedly scratched with a needle before a solution of the vaccine is applied. Almost all other vaccines today are delivered via intramuscular injection, with a needle going directly into the muscle, or through subcutaneous injection to the layer of tissue beneath the skin.
But Thomas Kupper, MD, chair of the Department of Dermatology, and colleagues, had reason to suspect that vaccines delivered by skin scarification may offer better protection against respiratory diseases. In a study published in Npj vaccines, Kupper and co-authors present results from preclinical studies suggesting skin scarification may help generate lung T cells and provide protection against infectious diseases, with implications for prevention of C19.
“We have known for years that this technique was a good way to generate T cells that would home to the skin, but our study shows that skin scarification is also an effective way to generate T cells that home to the lungs,” said Kupper. “Vaccine development today is focused on selecting the best antigen(s) for T cells and B cells. But for a vaccine to work to its full potential, it also needs to direct T cells to where they are needed most. For respiratory pathogens, that means getting T cells to the lungs.”
Historically, smallpox vaccines used live vaccinia virus (VACV). More recently, the FDA has approved the use of modified vaccinia Ankara (MVA), a modern alternative that lacks about 10% of the parent genome and cannot replicate in human cells, thus avoiding the serious side effects seen with VACV. MVA, as a smallpox vaccine, is injected subcutaneously.
Kupper and colleagues set out to determine if the skin scarification route of immunization with MVA could provoke a more effective T cell response than other routes of immunization. The team inoculated mice using either skin scarification, intramuscular, subcutaneous, or intradermal injection. Skin scarification generated more T cells, produced greater numbers of lung-specific T cells and provided superior protection against lethal viral doses than the others.
“We used to think that lung-homing T cells could only be generated by direct lung infection, but here we find overlap between T cells appearing after lung infection and T cells generated through skin scarification,” said Kupper.
The authors note that their work is preclinical — until clinical trials are conducted in humans, it’s unknown if the phenomenon seen in the mouse model can be replicated in people. But the work has spurred the Kupper lab to explore the potential for using the MVA vector and skin scarification technique to develop more powerful — and, potentially universal — vaccines against other infectious illnesses such as influenza and coronaviruses.
“We have known for a while that you can program T cells to go where you want them to go in the body — if you want protective T cells in the lungs, this is one way to achieve that. It is a serendipitous finding, but it seems to work very well,” said Kupper.

Source: https://www.eurekalert.org/pub_releases/2021-01/bawh-vdv012721.php

5. New 23andMe Tool Assesses Risk of C19 Becoming Severe

DNA-testing company 23andMe Inc. has launched a new tool that aims to predict an infected person’s risk of developing a severe case of C19, expanding the company’s bid to deliver actionable insight on health.
The company’s new C19 Severity Calculator was launched on Wednesday. It pulls data from a C19 study begun in April that queried more than a million participants on their ethnicity, lifestyle, height, weight, health conditions, genetics and experience with the disease, among other things. The calculator is based on data from about 10,000 study participants who tested positive for the virus, and more than 750 who were hospitalized.
An algorithm was created from the data that the company says can predict the likelihood of hospitalization for those infected. The ability of companies such as 23andMe to show that DNA tests can do more than help people explore their heritage is key to the growth of the consumer genomics industry.
“We quickly published the results and sought ways to help people benefit more directly from the research,” said Anne Wojcicki, 23andMe’s co-founder and chief executive officer. “We’ve found giving people actionable information – like this tool – drives meaningful results.”
Anyone can use the tool. Just input data points like age, sex and pre-existing health conditions, and the algorithm will spit out the percentage of people with those characteristics likely to be hospitalized with the virus.
The tool does not incorporate genetic factors in analyzing a person’s risk, but as more research uncovers associations between genetics and the coronavirus, that may come down the line.
For Wojcicki, becoming more valuable to the company’s customers by bringing them useful health information has been a key goal all along.
“More than 75% of our customers have told us they’ve taken a positive health action based on their 23andMe results,” she said in an interview. The company has not only sought to use its data to generate new genetic insights, but also to turn those insights into therapeutics.

In-House Drug

Last year, the Mountain View, California-based company licensed a drug it developed in-house to another company for the first time, and it also has a deal to collaborate on drug development with GlaxoSmithKline Plc, which took a $300 million stake in the company in 2018.
When the pandemic hit, 23andMe sought to demonstrate the value of genomics and a more personalized health care approach. In April, 23andMe launched its study to shed light on the role genetics play in the disease, research that could be especially helpful when it comes to C19.
Factors such as age and underlying health conditions can determine how people fare once they’ve contracted C19, but those things alone don’t explain the wide diversity of symptoms, or why some people contract the disease and others don’t.
Studying the genetics of the people who are more susceptible to the coronavirus (SARS-CoV-2) could help identify and protect those more at risk, as well as help speed treatment and drug development.

Blood-Type Research

In June, 23andMe published research that bolstered evidence that a person’s blood type can affect a person’s susceptibility to C19 by looking at a gene that influences blood type. Further study revealed another interesting finding that the company unveiled with the new tool: how much a person exercises seems to significantly influence their disease experience, regardless of other factors, according to Janie Shelton, a 23andMe senior scientist and epidemiologist.
“The things we found to be associated are informative, but they can’t necessarily predict the future,” she said. “What it does do is motivate people to continue their exercise habit.” Or, perhaps, start one.
The study only looked at correlations — it did not examine underlying mechanisms that might, for example, make exercise a good defense against the coronavirus. Exercise has been shown to benefit the immune system, however, Shelton said.
“This is sort of a first step where we’re trying to give people more accessible information about themselves,” Shelton said.

Source: https://www.bloomberg.com/news/articles/2021-02-02/u-k-covid-strain-picks-up-mutation-that-raises-vaccine-concern

6. Smartphone-Based C19 Test Delivers Results in 10 Minutes

Researchers at the University of Arizona are developing a C19 testing method that uses a smartphone microscope to analyze saliva samples and deliver results in about 10 minutes.
The University of Arizona research team, led by biomedical engineering professor Jeong-Yeol Yoon, aims to combine the speed of existing nasal swab antigen tests with the high accuracy of nasal swab PCR, or polymerase chain reaction, tests. The researchers are adapting an inexpensive method that they originally created to detect norovirus — the microbe famous for spreading on cruise ships — using a smartphone microscope.
They plan to use the method in conjunction with a saline swish-gargle test developed by Michael Worobey, head of the UArizona Department of Ecology and Evolutionary Biology and associate director of the University of Arizona BIO5 Institute.
The team’s latest research using water samples — done in collaboration with Kelly A. Reynolds, chair of the Department of Community, Environment and Policy in the UArizona Mel and Enid Zuckerman College of Public Health — is published today in Nature Protocols.
“We’ve outlined it so that other scientists can basically repeat what we did and create a norovirus-detecting device,” said Lane Breshears, a biomedical engineering doctoral student in Yoon’s lab. “Our goal is that if you want to adapt it for something else, like we’ve adapted it for C19, that you have all the ingredients you need to basically make your own device.”
Yoon — a BIO5 Institute member who is also a professor of biosystems engineering, animal and comparative biomedical sciences, and chemistry and biochemistry — is working with a large group of undergraduate and graduate students to develop the smartphone-based C19 detection method.
“I have a couple of friends who had C19 that were super frustrated, because their PCR results were taking six or seven days or they were getting false negatives from rapid antigen tests. But when they got the final PCR tests, they found out they had been sick, like they’d suspected,” said Katie Sosnowski, a biomedical engineering doctoral student who works in Yoon’s lab. “It’s really cool to be working on a detection platform that can get fast results that are also accurate.”

Cheaper, Simpler Detection

Traditional methods for detection of norovirus or other pathogens are often expensive, involve a large suite of laboratory equipment or require scientific expertise. The smartphone-based norovirus test developed at UArizona consists of a smartphone, a simple microscope and a piece of microfluidic paper — a wax-coated paper that guides the liquid sample to flow through specific channels. It is smaller and cheaper than other tests, with the components costing about $45.
The basis of the technology, described in a 2019 paper published in the journal ACS Omega, is relatively simple. Users introduce antibodies with fluorescent beads to a potentially contaminated water sample. If enough particles of the pathogen are present in the sample, several antibodies attach to each pathogen particle. Under a microscope, the pathogen particles show up as little clumps of fluorescent beads, which the user can then count. The process — adding beads to the sample, soaking a piece of paper in the sample, then taking a smartphone photograph of it under a microscope and counting the beads — takes about 10 to 15 minutes. It’s so simple that Yoon says a nonscientist could learn how to do it by watching a brief video.
The version of the technology described in the Nature Protocols paper makes further improvements, such as creating a 3D-printed housing for the microscope attachment and microfluidic paper chip. The paper also introduces a method called adaptive thresholding. Previously, researchers set a fixed value for what quantity of pathogen constituted a danger, which limited precision levels. The new version uses artificial intelligence to set the danger threshold and account for environmental differences, such as the type of smartphone and the quality of the paper.

On-Campus Impact

The researchers plan to partner with testing facilities at the University of Arizona to fine-tune their method as they adapt it for C19 detection. Pending approval of the university’s institutional review board, students who are already being tested on campus through other methods will have the option to provide written consent for their sample to be run through the smartphone-based testing device as well. Ultimately, the researchers envision distributing the device to campus hubs so that the average person — such as a resident assistant in a dorm — could test saliva samples from groups of people.
“Adapting a method designed to detect the norovirus — another highly contagious pathogen — is an outstanding example of our researchers pivoting in the face of the pandemic,” said University of Arizona President Robert C. Robbins. “This promising technology could allow us to provide fast, accurate, affordable tests to the campus community frequently and easily. We hope to make it a regular part of our ‘Test, Trace, Treat’ strategy, and that it will have a broader impact in mitigating the spread of the disease.”
Yoon and his team are also working on another idea, based on a 2018 paper they published in Chemistry—A European Journal, which is even simpler but leaves slightly more room for error. It involves the same technology, but instead of a smartphone microscope and specially designed enclosure, users would only need to download a smartphone app and use a microfluidic chip stamped with a QR code.
“Unlike the fluorescent microscope technique, where you get the chip into just the right position, you just take a snapshot of the chip,” said biomedical engineering master’s student Pat Akarapipad. “No matter the angle or distance the photo is taken from, the smartphone app can use AI and the QR code to account for variances and run calculations accordingly.”
The method requires no training, so, if perfected, it could potentially allow students to pick up microfluidic chips from a campus location and test their own samples. The team is also working with other members of the university’s C19 testing group, including Deepta Bhattacharya, an associate professor in the Department of Immunobiology.

Source: https://scitechdaily.com/smartphone-based-covid-19-test-developed-that-delivers-results-in-10-minutes/

7. 10-minute C19 diagnostic test that wage workers can afford

A test that detects antibodies to the novel coronavirus in 10 minutes and costs only a fifth of the market average has been developed by researchers at the University of São Paulo’s São Carlos Chemistry Institute (IQSC-USP) and Brazilian startup Biolinker, with São Paulo Research Foundation – FAPESP’s support.
The device works similarly to the rapid tests available now in pharmacies. It analyzes a drop of blood, and two red LEDs light up if it detects the presence of immunoglobulin G (IgG) antibodies, which are produced in the acute phase of C19 (ten days after the onset of symptoms on average).
“The more antibodies there are in the blood, the brighter the red color. We believe this means the test can also be used to monitor the response to vaccination. We know not everyone develops protective immunity after being vaccinated. We also know the level of antibodies declines over time,” Frank Crespilho, a professor at IQSC-USP and principal investigator for the study, told.
The study was conducted by two of Crespilho’s students, Karla Castro and Isabela Mattioli. According to Crespilho, the technology can easily be adapted to the novel SARS-CoV-2 variants, if necessary.
The test can be sold for 30 Brazilian Reais (now about 5.50 US dollars) once it has been approved by ANVISA, the national health surveillance authority, he said. Similar tests can currently be purchased in Brazil for about 140 BRL. The researchers optimized the quantity of raw materials and reagents to lower its production cost and developed a technology based on nanoparticles to facilitate IgG detection.
“We combined a gold nanoparticle [which originates the red color] with a piece of the virus’s spike protein recognized by human antibodies. This bioconjugate is about a millionth of the size of a human hair,” Crespilho said.
The virus’s spikes form the corona-like structure that suggested its family name. They enable the virus to enter and infect human cells by binding to the ACE-2 receptor on the cell surface.
To develop the molecule used in the test device, Biolinker’s researchers worked in the laboratory to synthesize the docking tip of the spike protein, known as the receptor-binding domain (RBD). According to Mona Oliveira, Biolinker’s chief science officer and co-founder, they used a recombinant DNA technology involving bacteria genetically modified to express the viral protein in vitro. This part of the process was supported by São Paulo Research Foundatin – FAPESP’s Innovative Research in Small Business Program (PIPE) and FINEP, the Brazilian Innovation Agency.
“All reagents and other inputs used by the device are produced in Brazil, which helps reduce the cost. We worked around the clock to develop it in just four months,” said Crespilho, who heads the University of São Paulo’s Bioelectrochemistry and Interface Laboratory. The aim is to expand testing in Brazil by making it affordable for low-income families. “We designed it as a means of enabling mass testing at a competitive cost in line with economic reality,” he said.
Testing is underway to determine the accuracy of the method developed by the IQSC-USP group. The scientists are also working on a plan to ramp up production and have other groups perform trials to validate the methodology. Around 500 units will be produced and tested using samples from patients treated at São Paulo State University (UNESP) in Botucatu, the Federal University of São Carlos (UFSCar) and the Federal University of São Paulo (UNIFESP).
“We’re also negotiating with groups in the Northeast region,” Crespilho said. “Validation will take about a month. Then we’ll apply for approval by ANVISA.”

Source: https://www.eurekalert.org/pub_releases/2021-02/fda-rd1020221.php

F. Improved & Potential Treatments

1. Powerful Antiviral Treatment for C19 Discovered That Could Change How Epidemics Are Managed

Researchers from the University of Nottingham have discovered a novel antiviral property of a drug that could have major implications in how future epidemics / pandemics — including C19 — are managed.
The study, published in Viruses, shows that thapsigargin is a promising broad spectrum antiviral, highly effective against C19 virus (SARS-CoV-2), a common cold coronavirus, respiratory syncytial virus (RSV), and the influenza A virus.
Given that acute respiratory virus infections caused by different viruses are clinically indistinguishable on presentation, an effective broad-spectrum that can target different virus types at the same time could significantly improve clinical management. An antiviral of this type could potentially be made available for community use to control active infection and its spread.
The study is a collaborative project led by Professor Kin-Chow Chang and experts at the University of Nottingham (Schools of Veterinary Medicine and Sciences, Biosciences, Pharmacy, Medicine, and Chemistry), and colleagues at the Animal and Plant Health Agency (APHA), China Agricultural University and the Pirbright Institute.
In this ground-breaking study, the team of experts found that the plant-derived antiviral, at small doses, triggers a highly effective broad-spectrum host-centered antiviral innate immune response against three major types of human respiratory viruses — including C19.
The key features based on cell and animal studies, which make thapsigargin a promising antiviral are that it is:
- effective against viral infection when used before or during active infection;
- able to prevent a virus from making new copies of itself in cells for at least 48 hours after a single 30-minute exposure;
- stable in acidic pH, as found in the stomach, and therefore can be taken orally, so could be administered without the need for injections or hospital admission;
- not sensitive to virus resistance;
- at least several hundred-fold more effective than current antiviral options;
- just as effective in blocking combined infection with coronavirus and influenza A virus as in single-virus infection; and
- safe as an antiviral (a derivative of thapsigargin has been tested in prostate cancer).
Professor Chang said: “Whilst we are still at the early stages of research into this antiviral and its impact on how viruses such as C19 can be treated, these findings are hugely significant.”
“The current pandemic highlights the need for effective antivirals to treat active infections, as well as vaccines, to prevent the infection. Given that future pandemics are likely to be of animal origin, where animal to human (zoonotic) and reverse zoonotic (human to animal) spread take place, a new generation of antivirals, such as thapsigargin, could play a key role in the control and treatment of important viral infections in both humans and animals.”
Indeed, influenza virus, coronavirus, and RSV are global pathogens of humans as well as animals. Thapsigargin represents a lead compound in the development of a new generation of powerful host-centered antivirals (as opposed to conventional antiviral drugs that directly target viruses) that could even be adopted in a holistic “One Health” approach to control human and animal viruses.
Professor Chang adds: “Although more testing is clearly needed, current findings strongly indicate that thapsigargin and its derivatives are promising antiviral treatments against C19 and influenza virus, and have the potential to defend us against the next Disease X pandemic.”

Source: https://scitechdaily.com/powerful-antiviral-treatment-for-covid-19-discovered-that-could-change-how-epidemics-are-managed/

2. How Vitamins, Steroids and Potential Antivirals Might Help Combat C19

Evidence is emerging that vitamin D — and possibly vitamins K and A — might help combat C19. A new study from the University of Bristol published in the journal of the German Chemical Society Angewandte Chemie has shown how they — and other antiviral drugs — might work. The research indicates that these dietary supplements and compounds could bind to the viral spike protein and so might reduce coronavirus (SARS-CoV-2) infectivity. In contrast, cholesterol may increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious disease.
Recently, Bristol researchers showed that linoleic acid binds to a specific site in the viral spike protein, and that by doing so, it locks the spike into a closed, less infective form. Now, a research team has used computational methods to search for other compounds that might have the same effect, as potential treatments. They hope to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with a human protein (ACE2). New anti-viral drugs can take years to design, develop and test, so the researchers looked through a library of approved drugs and vitamins to identify those which might bind to this recently discovered ‘druggable pocket’ inside the SARS-CoV-2 spike protein.
The team first studied the effects of linoleic acid on the spike, using computational simulations to show that it stabilizes the closed form. Further simulations showed that dexamethasone — which is an effective treatment for C19 — might also bind to this site and help reduce viral infectivity in addition to its effects on the human immune system.
The team then conducted simulations to see which other compounds bind to the fatty acid site. This identified some drugs that have been found by experiments to be active against the virus, suggesting that this may be one mechanism by which they prevent viral replication such as, by locking the spike structure in the same way as linoleic acid.
The findings suggested several drug candidates among available pharmaceuticals and dietary components, including some that have been found to slow SARS-CoV-2 reproduction in the laboratory. These have the potential to bind to the SARS-CoV-2 spike protein and may help to prevent cell entry.
The simulations also predicted that the fat-soluble vitamins D, K and A bind to the spike in the same way making the spikeless able to infect cells.
Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modelling) in the School of Biochemistry, who modeled the spike, explained: “Our findings help explain how some vitamins may play a more direct role in combatting COVID than their conventional support of the human immune system.
“Obesity is a major risk factor for severe COVID. Vitamin D is fat-soluble and tends to accumulate in fatty tissue. This can lower the amount of vitamin D available to obese individuals. Countries in which some of these vitamin deficiencies are more common have also suffered badly during the course of the pandemic. Our research suggests that some essential vitamins and fatty acids including linoleic acid may contribute to impeding the spike/ACE2 interaction. Deficiency in any one of them may make it easier for the virus to infect.”
Pre-existing high cholesterol levels have been associated with increased risk for severe C19. Reports that the SARS-CoV-2 spike protein binds cholesterol led the team to investigate whether it could bind at the fatty acid-binding site. Their simulations indicate that it could bind, but that it may have a destabilizing effect on the spike’s locked conformation, and favor the open, more infective conformation.
Dr. Shoemark continued: “We know that the use of cholesterol-lowering statins reduces the risk of developing severe COVID and shortens recovery time in less severe cases. Whether cholesterol de-stabilizes the “benign”, closed conformation or not, our results suggest that by directly interacting with the spike, the virus could sequester cholesterol to achieve the local concentrations required to facilitate cell entry and this may also account for the observed loss of circulating cholesterol post-infection.”
Professor Adrian Mulholland, of Bristol’s School of Chemistry, added: “Our simulations show how some molecules binding at the linoleic acid site affect the spike’s dynamics and lock it closed. They also show that drugs and vitamins active against the virus may work in the same way. Targeting this site may be a route to new anti-viral drugs. A next step would be to look at effects of dietary supplements and test viral replication in cells.”
Alison Derbenwick Miller, Vice President, Oracle for Research, said: “It’s incredibly exciting that researchers are gaining new insights into how SARS-CoV-2 interacts with human cells, which ultimately will lead to new ways to fight C19. We are delighted that Oracle’s high-performance cloud infrastructure is helping to advance this kind of world-changing research. Growing a globally-connected community of cloud-powered researchers is exactly what Oracle for Research is designed to do.”

Source: https://scitechdaily.com/how-vitamins-steroids-and-potential-antivirals-might-might-help-combat-covid-19/

3. 18 FDA-approved drugs that could halt coronavirus infection earlier

A team of Boston University researchers—hailing from BU’s National Emerging Infectious Diseases Laboratories (NEIDL), the Center for Regenerative Medicine (CReM) at BU’s Medical Campus, and BU’s Center for Network Systems Biology (CNSB)—embarked on a months-long, collaborative and interdisciplinary quest, combining multiple areas of expertise in virology, stem cell–derived lung tissue
The result of that challenging and massive undertaking? The BU team has revealed the most comprehensive map to date of all the molecular activities that are triggered inside lung cells at the onset of coronavirus infection. They also discovered there are at least 18 existing, FDA-approved drugs that could potentially be repurposed to combat C19 infections shortly after a person becomes infected. Experimentally, five of those drugs reduced coronavirus spread in human lung cells by more than 90%. Their findings were recently published in Molecular Cell.
Now, academic and industry collaborators from around the world are in contact with the team about next steps to move their findings from bench to bedside, the researchers say. (Although C19 vaccines are starting to be rolled out, it’s expected to take the better part of a year for enough people to be vaccinated to create herd immunity. And there are no guarantees that the current vaccine formulations will be as effective against future coronavirus (SARS-CoV-2) strains that could emerge over time.) More effective and well-timed therapeutic interventions could help reduce the overall number of deaths related to C19 infections.
“What makes this research unusual is that we looked at very early time points [of infection], at just one hour after the virus infects lung cells. It was scary to see that the virus already starts to damage the cells so early during infection,” says Elke Mühlberger, one of the study’s senior investigators and a virologist at BU’s NEIDL. She typically works with some of the world’s most lethal viruses like Ebola and Marburg.
“The most striking aspect is how many molecular pathways are impacted by the virus,” says Andrew Emili, another of the study’s senior investigators, and the director of BU’s CNSB, which specializes in proteomics and deep sequencing of molecular interactions. “The virus does wholesale remodeling of the lung cells—it’s amazing the degree to which the virus commandeers the cells it infects.”
Viruses can’t replicate themselves because they lack the molecular machinery for manufacturing proteins—that’s why they rely on infecting cells to hijack the cells’ internal machinery and use it to spread their own genetic material. When SARS-CoV-2 takes over, it completely changes the cells’ metabolic processes, Emili says, and even damages the cells’ nuclear membranes within three to six hours after infection, which the team found surprising. In contrast, “cells infected with the deadly Ebola virus don’t show any obvious structural changes at these early time points of infection, and even at late stages of infection, the nuclear membrane is still intact,” Mühlberger says.
The nuclear membrane surrounds the nucleus, which holds the majority of a cell’s genetic information and controls and regulates normal cellular functions. With the cell nucleus compromised by SARS-CoV-2, things rapidly take a bad turn for the entire cell. Under siege, the cells—which normally play a role in maintaining the essential gas exchange of oxygen and carbon dioxide that occurs when we breathe—die. As the cells die, they also emit distress signals that boost inflammation, triggering a cascade of biological activity that speeds up cell death and can eventually lead to pneumonia, acute respiratory distress, and lung failure.
“I couldn’t have predicted a lot of these pathways, most of them were news to me,” says Andrew Wilson, one of the study’s senior authors, a CReM scientist, and a pulmonologist at Boston Medical Center (BMC), BU’s teaching hospital. At BMC, Boston’s safety net hospital, Wilson has been on the front lines of the C19 pandemic since March 2020, trying to treat and save the sickest patients in the hospital’s ICU. “That’s why our [experimental] model is so valuable.”
The team leveraged the CReM’s organoid expertise to grow human lung air sac cells, the type of cell that lines the inside of lungs. Air sac cells are usually difficult to grow and maintain in traditional culture and difficult to extract directly from patients for research purposes. That’s why much coronavirus research to date by other labs has relied on the use of more readily available cell types, like kidney cells from monkeys. The problem with that is kidney cells from monkeys don’t react the same way to coronavirus infection as lung cells from humans do, making them a poor model for studying the virus—whatever is learned from them doesn’t easily translate into clinically relevant findings for treating human patients.
“Our organoids, developed by our CReM faculty, are engineered from stem cells—they’re not identical to the living, breathing cells inside our bodies, but they are the closest thing to it,” says Darrell Kotton, one of the study’s senior authors. He is a director of the CReM and a pulmonologist at BMC, where he has worked alongside Wilson in the ICU treating C19 patients. The two of them often collaborated with Mühlberger, Emili, and other members of their research team via Zoom calls that they managed to join during brief moments of calm in the ICU.
In another recent study using the CReM’s engineered human lung cells, the research team confirmed that existing drugs remdesivir and camostat are effective in combating the virus, though neither is a perfect fix for controlling the inflammation that C19 causes. Remdesivir, a broad-use antiviral, has already been used clinically in coronavirus patients. But based on the new study’s findings that the virus does serious damage to cells within hours, setting off inflammation, the researchers say there’s likely not much that antiviral drugs like remdesivir can do once an infection has advanced to the point where someone would need to be put on a ventilator in the ICU. “[Giving remdesivir] can’t save lives if the disease has already progressed,” Emili says.
Seeing how masterfully SARS-CoV-2 commandeers human cells and subverts them to do the manufacturing work of replicating the viral genome, it reminded the researchers of another deadly invader.
“I was surprised that there are so many similarities between cancer cells and SARS-CoV-2-infected cells,” Mühlberger says. The team screened a number of cancer drugs as part of their study and found that several of them are able to block SARS-CoV-2 from multiplying. Like viruses, cancer cells want to replicate their own genomes, dividing over and over again. To do that, they need to produce a lot of pyrimidine, a basic building block for genetic material. Interrupting the production of pyrimidine—using a cancer drug designed for that purpose—also blocks the SARS-CoV-2 genome from being built. But Mühlberger cautions that cancer drugs typically have a lot of side effects. “Do we really want to use that heavy stuff against a virus?” she says. More studies will be needed to weigh the pros and cons of such an approach.
The findings of their latest study took the four senior investigators and scientists, postdoctoral fellows, and graduate students from their laboratories almost four months, working nearly around the clock, to complete the research. Of critical importance to the team’s leaders was making sure that the experimental setup had rock-solid foundations in mimicking what’s actually happening when the SARS-CoV-2 virus infects people.
“Science is the answer—if we use science to ask the lung cells what goes wrong when they are infected with coronavirus, the cells will tell us,” Kotton says. “Objective scientific data gives us hints at what to do and has lessons to teach us. It can reveal a path out of this pandemic.”
He’s particularly excited about the outreach the team has received from collaborators around the world. “People with expertise in supercomputers and machine learning are excited about using those tools and the datasets from our publication to identify the most promising drug targets [for treating C19],” he says.
Kotton says the theme that’s become obvious among C19 clinicians and scientists is understanding that timing is key. “Once a patient is on a ventilator in the ICU, we feel limited in what we can do for their body,” he says. “Timing is everything, it’s crucial to identify early windows of opportunity for intervention. You can keep guessing and hope we get lucky—or you [do the research] to actually understand the infection from its inception, and take the guesswork out of drug development.”

Source: https://scitechdaily.com/how-coronavirus-damages-lung-cells-within-mere-hours-and-what-drugs-could-halt-covid-19-infection/

4. Scientists devise method for improving safety of drug used to treat C19

A collaboration led by Scripps Research has developed a way to separate the beneficial anti-inflammatory properties of a group of steroids called glucocorticoids from some of their unwanted side-effects, through an optimization process they named “ligand class analysis.”
Their process enabled them to engineer two new, drug-like compounds that show steroidal anti-inflammatory action and other specific traits. One boosts muscle and energy supply, while the other reduces risk of muscle-wasting and bone loss typical of such drugs.
Their report, titled, “Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling,” appeared Jan. 28 in the journal Nature Chemical Biology.
Glucocorticoids are steroid hormones, a group that includes cortisone, prednisone and dexamethasone. Among the most frequently prescribed of medications, their anti-inflammatory properties make them useful in an array of forms and doses.
Glucocorticoids are used as injections for hip or back pain, tablets for autoimmune disease, nasal spray for sinus congestion, anti-itch cremes for soothing rashes or insect bites, and more.
Most recently, the glucocorticoid drug dexamethasone has become the standard of care for C19 treatment later in illness, as it can help quiet overaggressive immune attacks in delicate lung tissue and blood vessels.
But glucocorticoids are also among the more problematic of medicines, as prolonged use or high doses can lead to adverse events including high blood pressure, muscle wasting, bone loss, vulnerability to infections, vision problems, anxiety, swelling, weight gain, high blood sugar, insulin resistance, diabetes, and more, while naturally occurring glucocorticoids in the body can contribute to prostate cancer progression.

Pursuing safety

A key goal of the team was to engineer more precise glucocorticoids able to act in tissue-specific or activity-specific way, while limiting specific adverse events, says the study’s lead author, Kendall Nettles, PhD, associate professor of Integrative and Structural Biology at the Scripps Research, Florida campus.
“There is a great unmet need to improve glucocorticoids,” Nettles says. “We asked, ‘Can we develop glucocorticoids that have more selective effects on inflammation and the immune system, instead of hitting the body with a hammer?’ This method is showing that we can do that now.”
The project pooled the expertise of many collaborators, in areas including chemistry, bioinformatics, structural biology, proteomics, genomics, cell metabolism and more. Contributors included Scripps Research, Florida-based faculty and their scientific staff and students; a researcher from the institute’s California-based drug discovery division, Calibr, and scientists from Weill Cornell Medicine, Emory University School of Medicine, the National Cancer Institute and others.
Nettles says their “ligand class analysis” process began with selection of a known corticosteroid compound. Scripps Research chemist Theodore Kamenecka, PhD, modified the compound in many ways to build a collection of new molecules.
One substitution at a time, the scientists created 22 new compounds that showed an ability to actively bind with cell receptors for steroids. They then devised an experimental platform for testing precisely how these compounds affected muscle, bone and lung cells, to indicate each one’s risk of causing muscle loss or bone loss, while keeping anti-inflammatory activity.
One of the greatest challenges they encountered was devising a way to accurately test the molecules in cultured cells, Nettles says. At first, they seemed to require 1,000 times more compound than expected to measure impact.

Stress produces results

First author Nelson Bruno had the breakthrough idea of testing only after stress, specifically, fasting followed by brief insulin challenge. That’s because stress is the trigger for release of endogenous steroid hormones in real life, Nettles explains.
“It took us two years just to develop the experimental assays to reproduce the effects of what glucocorticoids do in people,” Nettles says. “We found we needed realistic physiology.”
They also used a machine learning approach to predict how the compounds would affect insulin receptor signaling, gene transcription, protein balance and glucose disposal in the cells, depending on chemical structure.
Through repeated challenges and tests in the cells and in mice, they settled on two compounds, SR11466 and SR16024, as ones with medically useful traits including inflammation control, plus muscle-sparing ability, or mitochondria-building potential. Mitochondria convert cellular nutrients into energy.
The process they developed to refine the compounds has implications well beyond the improvement of glucocorticoids, Nettles adds. It can power more-selective drug-discovery for any number of medicines that work via the cell surface and nuclear receptors to impact signaling and gene transcription in cells, he says.
This project started long before the C19 pandemic began, Nettles says, but it has potential to benefit people sickened with C19. In the context of an infectious disease, the ideal anti-inflammatory would be one that suppressed overly aggressive immune attack without impairing ability to fight off infection, so that’s the next goal, he says. More work is needed to address bone loss risk as well, he says.
“These drugs could be used more widely if we could reduce the side-effects profile,” Nettles says. “We brought together many recent scientific advances to address a significant problem that affects huge numbers of people. Our findings show that using ligand class analysis, we can potentially improve the safety and specificity of steroids and other needed medicines.”

Source: https://www.eurekalert.org/pub_releases/2021-02/sri-tss020221.php

G. Concerns & Unknowns

1. New diabetes cases linked to C19

Mihail Zilbermint is used to treating diabetes — he heads a special team that cares for patients with the metabolic disorder at Suburban Hospital in Bethesda, Md. But as the hospital admitted increasing numbers of patients with C19, his caseload ballooned.
“Before, we used to manage maybe 18 patients per day,” he said. Now his team cares for as many as 30 daily.
Many of those patients had no prior history of diabetes. Some who developed elevated blood sugar while they had C19, the illness caused by the novel coronavirus, returned to normal by the time they left the hospital. Others went home with a diagnosis of full-blown diabetes. “We’ve definitely seen an uptick in patients who are newly diagnosed,” Zilbermint said.
Although C19 often attacks the lungs, it is increasingly associated with a range of problems including blood clots, neurological disorders, and kidney and heart damage. Researchers say new-onset diabetes may soon be added to those complications — both Type 1, in which people cannot make the insulin needed to regulate their blood sugar, and Type 2, in which they make too little insulin or become resistant to their insulin, causing their blood sugar levels to rise. But scientists do not know whether C19 might hasten already developing problems or actually cause them — or both.
As early as January 2020, doctors in Wuhan, China, noticed elevated blood sugar in patients with C19. Physicians in Italy, another early hot spot, wondered whether diabetes diagnoses might follow, given the long-observed association between viral infections and the onset of diabetes. That association was seen in past outbreaks of other coronavirus illnesses such as SARS.
A year after the pandemic began, the precise nature and scope of the covid-diabetes link remain a mystery. Many of those who develop diabetes during or after C19 have risk factors, such as obesity or a family history of the disease. Elevated blood glucose levels also are common among those taking dexamethasone, a steroid that is a front-line treatment for C19. But cases also have occurred in patients with no known risk factors or prior health concerns. And some cases develop months after the body has cleared the virus.
John Kunkel, a 47-year-old banking executive in Evening Shade, Ark., was one of the surprise cases. He was hospitalized with C19 in early July. During a follow-up visit with his doctor, he learned he had dangerously high blood glucose levels and was readmitted. Kunkel has since received a diagnosis of Type 2 diabetes.
“I had no preexisting health issues,” he said. “I was blown away. Why?”
Kunkel has had five emergency room visits and three hospital stays since getting C19. He recently lost his job because he was unable to return to work, given his continuing health problems. “Will you get your life back?” he asked. “Nobody knows.”
As many as 14.4% of people hospitalized with severe C19 developed diabetes, according to a global analysis published Nov. 27 in the journal Diabetes, Obesity and Metabolism. The international group of researchers sifted through reports of uncontrolled hyperglycemia, or high blood sugar, in more than 3,700 C19 patients across eight studies. While those diagnoses might be the result of a long-observed response to severe illness, or to treatment with steroids, the authors wrote, a direct effect from C19 “should also be considered.”
Concerns that C19 might be directly implicated also were supported, they said, by the exceptionally high doses of insulin that diabetes patients with severe C19 often require and the dangerous complications they develop.
Researchers do not understand exactly how C19 might trigger Type 1 or Type 2 diabetes, or whether the cases are temporary or permanent. But they are racing to find answers to these and other questions, including whether the novel coronavirus may have spawned an entirely new type of diabetes that might play out differently from the traditional forms of the disease.
Francesco Rubino, a diabetes surgery professor at King’s College London, is convinced there is an underlying connection between the diseases.
Over the summer, he and a group of other diabetes experts launched a global registry of patients with C19-related diabetes. After they spread the word with an editorial in the New England Journal of Medicine, more than 350 institutions from across the world responded, he said.
The database is accumulating patients — over 150 so far — although it will take months for researchers to sift through the data to draw any conclusions. “We really need to dig deeper,” Rubino said. “But it sounds like we do have a real problem with covid and diabetes.”
Some of the cases reported to his database do not fit the usual profile of Type 1 diabetes, in which the pancreas produces little or no insulin, or Type 2, in which people become insulin resistant, he said. Usually, a patient with one type of diabetes will experience specific complications; for instance, those with Type 1 may burn through their fat stores, or those with Type 2 may experience a syndrome that can involve severe dehydration and coma as the body pumps excess blood sugar into the urine. In some patients with C19, though, complications cross types.
“There’s a good chance that the mechanism of the diabetes isn’t typical,” Rubino said. “There could be a hybrid form. It’s concerning.”
Rubino is especially worried about reports of diabetes diagnoses after mild or asymptomatic coronavirus infections. As the number of novel coronavirus infections continues to rise, he said, “you could see a significant new volume of diabetes diagnoses.”
Diabetes already is increasing at an alarming rate in the United States. An estimated 34.2 million people, or 10.5% of the population, have the disorder, according to federal health data. And approximately 1 in 3 Americans, or 88 million people, have prediabetes, which indicates they are on a path to Type 2. If left uncontrolled, the disease can damage many parts of the body and is associated with serious complications including heart disease, stroke, blindness, kidney failure and nerve damage.
But whether those with diabetes that is newly diagnosed after C19 will have a lifelong problem is unclear. After the 2003 SARS pandemic, Chinese researchers tracked 39 patients with no history of diabetes who had developed acute diabetes within days of hospitalization with SARS. For all but six, blood sugar level had fallen by the time they were discharged, and only two still had diabetes after two years. The researchers also found evidence that the SARS virus might attack insulin-producing beta cells in the pancreas.
Beta cells play starring roles in both types of diabetes: The bodies of those with Type 1 attack and destroy the cells altogether, halting insulin production. Type 2 diabetics become resistant to the insulin they produce, so the beta cells make more and more, and eventually are worn out.
“If scientists could figure out how or if viral infection can damage beta cells, or what role viruses play in the development of the disease, it would be a real turning point,” said Katie Colbert Coate, a diabetes researcher and research instructor in medicine at Vanderbilt University Medical Center.
Though people with diabetes are no more susceptible to contracting C19 than those without, they are at much higher risk of severe complications or death once they do. In the early days of the pandemic, just over a third of those who died of C19 in British hospitals had preexisting cases of diabetes. Doctors in Wuhan also noticed that those with newly diagnosed diabetes were more likely to need intensive care than those who had diabetes before they contracted C19.
New diagnoses of diabetes in people with no classic risk factors also are scattered throughout case reports: A 37-year-old, previously healthy Chinese man who went to the hospital with a severe, and in some cases fatal, diabetes complication; a 19-year-old German who developed Type 1 diabetes five to seven weeks after a novel coronavirus infection but who lacked the antibodies commonly associated with the autoimmune disease.
Doctors at Children’s Hospital Los Angeles, meanwhile, noticed an increase in the number of Type 2 diagnoses in children, as well as a severe complication of diabetes. After some of them showed evidence of past coronavirus infections, Senta Georgia, an investigator in the hospital’s Saban Research Institute, began looking deeper. Her research, which repurposes tissue from primates used in vaccine tests, is undergoing peer review.
“Only with the scientific public square can we put all of this data out there, evaluate its strengths and weaknesses … until we really get the information we need,” Georgia said.
Such reports also have increased the sense of urgency for researchers like Coate, who dropped other work and began looking for keys to understanding the mechanism of the disease by examining how C19 might damage beta cells or other structures in the pancreas. She and others are asking whether certain covid symptoms predict whether a patient is vulnerable to diabetes and, most important, whether the disease’s onset is an effect of the immune response or a result of the virus directly attacking insulin-producing cells.
ACE2 receptor cells, the novel coronavirus’s entryway into the body, could provide one answer. When the spike proteins that surround the virus latch onto a host cell with an ACE2 receptor, they open up a cellular doorway that allows the virus to hijack the cell.
Strong evidence of ACE2 receptors on beta cells could confirm the long-standing suspicion that viruses trigger diabetes. But the research findings are inconclusive: Since the pancreas breaks down quickly after death, obtaining good samples from autopsied humans is difficult. And each study has its own limitations.
Last year, Cornell University researchers grew human pancreas cells and managed to infect them with SARS-CoV-2, as the novel coronavirus is technically known. They found ACE2 receptors on the cells, but the cells had been cultivated in a laboratory, not a human body.
Coate and her colleagues at Vanderbilt University were able to confirm the presence of ACE2 receptors in the physical structures of the pancreas, but their study focused on patients without C19 and found no evidence of the receptors on the insulin-producing beta cells. An Italian study did find the receptors in beta cells, but the donors did not have C19, either. Until receptors in pancreatic beta cells in tissue from C19 patients can be consistently confirmed by other researchers, the hunt for the mechanism underlying the diabetes-C19 connection continues. So does research on ways C19 might harm other parts of the endocrine system, which also might play a role in the disease mechanism.
For newly diagnosed patients such as nurse practitioner Tanisha Flowers, the answers can’t come soon enough.
Infected in April while working in a C19 ward in a Richmond hospital, the 40-year-old was diagnosed with diabetes in October. She now takes daily medications, watches her diet and is all too aware that she may be diabetic for life.
“I’m not myself anymore,” Flowers said. “No one knows what the lasting outcomes are.”

Source: https://www.washingtonpost.com/health/2021/02/01/covid-new-onset-diabetes/

2. How the Coronavirus Turns the Body Against Itself

The coronavirus can warp the body’s defenses in many ways — disarming the body’s early warning systems, for example, or causing immune cells to misfire. But a spate of new studies suggests another insidious consequence: The infection can trigger the production of antibodies that mistakenly attack the patient’s own tissues instead of the virus.
The latest report, published online this week, suggests that so-called autoantibodies can persist months after the infection has resolved, perhaps causing irreparable harm. If other studies confirm the finding, it may explain some of the lingering symptoms in people who have recovered from C19. The syndrome, sometimes referred to as long Covid, can include dementia, “brain fog” and joint pain.
Autoantibodies are not new to science: They are the misguided soldiers of the immune system, tied to debilitating diseases such as lupus and rheumatoid arthritis, which arise when the body attacks its own tissues.
The newest study is small, with just nine patients, five of whom had autoantibodies for at least seven months. It has not yet undergone peer review for publication, and the authors urged caution in interpreting the results.
“It’s a signal; it is not definitive,” said Dr. Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Center, who led the study. “We don’t know how prevalent it is, and whether or not it can be linked to long Covid.”
The question of autoimmunity following coronavirus infection is urgent and important, Dr. Bhadelia added. As many as one in three survivors of C19 say they still experience symptoms.
“This is a real phenomenon,” she said. “We’re looking at a second pandemic of people with ongoing potential disability who may not be able to return to work, and that’s a huge impact on the health systems.”
A growing body of evidence suggests that autoimmunity contributes to the severity of C19 in some people. A study published online in October found that among 52 patients with severe C19, more than 70% carried antibodies against their own DNA and against proteins that help with blood clotting.
In another study, also published online in October, researchers discovered autoantibodies to carbohydrates made by the body in C19 patients, which could explain neurological symptoms. And a study in the journal Science Translational Medicine in November found that half of patients hospitalized for C19 had at least transient autoantibodies that cause clots and blockages in blood vessels.
The gathering research raises the worrying possibility that lingering autoantibodies might lead to autoimmune disease in some people infected with the coronavirus.
“Once these autoantibodies are induced, there is no going back,” said Akiko Iwasaki, an immunologist at Yale University. “They will be a permanent part of the person’s immune system.”
She added: “What does it do to vaccine response? What does it do to newly acquired infections? These are all questions that will have to be addressed.”
Dr. Iwasaki’s team showed in December that severely ill patients had dramatic increases in a wide array of autoantibodies that target parts of the immune system, brain cells, connective tissue and clotting factors.
“We really see broadly reactive autoantibody responses in these patients,” Dr. Iwasaki said. She had suspected that autoimmunity might play some role, but “even I didn’t expect to see this much auto-reactivity.”
Dr. Iwasaki and her colleagues collected blood from 172 patients with a range of symptoms, 22 health care workers who had been infected, and 30 uninfected health care workers.
One in five infected patients had autoantibodies to five proteins in their own bodies, and up to 80% to at least one protein, the researchers found. Patients with severe C19 had many more of these antibodies, which hindered their immune responses and exacerbated illness. Of 15 patients who died during the study, 14 had autoantibodies to at least one constituent of the immune system.
The study convincingly shows that autoantibodies “alter the course of disease,” said Marion Pepper, an immunologist at the University of Washington in Seattle who was not involved in the research.
Autoimmunity after an illness is not unique to the coronavirus. Other intensely inflammatory infections, including malaria, leprosy and respiratory viruses, are also known to trigger autoantibodies. But autoimmunity and C19 may be a particularly hazardous mix, experts said.
One analysis of nearly 170,000 people with rare autoimmune rheumatic diseases like lupus and scleroderma indicated that they face increased odds of death from C19. And a study of more than 130,000 people found that autoimmune conditions like Type 1 diabetes, psoriasis and rheumatoid arthritis increase the risk of respiratory complications and death from C19.
Some of the antibodies seemed to be the result of inborn defects in the immune system. For example, a study in the journal Science in October found that about 10 percent of severely ill C19 patients had existing autoantibodies that attacked key components of the immune system that were supposed to kick in after exposure to the virus. Without that rapid response, the body’s defense is hopelessly delayed, fighting a losing battle against the multiplying virus.
Yet the mere presence of autoantibodies does not indicate harm. They are in the general population and don’t always lead to illness, some experts noted.
“Anywhere from 10 to 15% of the population has some level of this auto-reactivity,” said Dr. Iñaki Sanz, an immunologist at Emory University. “The issue is that you need many other events downstream of the autoantibodies to induce disease.”
At least in some patients, autoantibodies clearly emerged as a result of the illness, Dr. Iwasaki’s study showed. Extreme inflammation caused by viral infections can cause cells to burst open, spewing their contents and befuddling the immune system’s ability to distinguish “self” from “other.”
But autoantibodies induced in this manner may level off after a few months, said Dr. Shiv Pillai, an immunologist at Harvard University: “Probably in the vast majority of C19 patients, autoantibodies emerge in the acute phase, then decline.”
“That being said — yes, it would be interesting if long Covid might be explained by specific autoantibodies,” he added.
Several researchers, including Dr. Bhadelia and Dr. Iwasaki, are following patients over time to see how long autoantibodies persist and whether they wreak permanent damage. Although scientists have known that acute infections can trigger their presence, the phenomenon has never been studied in such detail.
“That’s maybe the one silver lining here,” Dr. Pepper said. “We’re going to learn some fundamental principles about acute viral infections in people which haven’t been easy to study in this way before.”

Source: https://www.nytimes.com/2021/01/28/health/coronavirus-antibodies-immunity.html

3. Dangerous new coronavirus strains may incubate in C19’s sickest

Among the 100 million people around the world who have battled coronavirus infections, scientists are turning to the case of a 45-year-old C19 patient in Boston to understand how the virus is able to outwit humans.
During his 154-day illness — one of the longest on record — the patient’s body became a crucible of riotous viral mutation. He offered the world one of the first sightings of a key mutation in the virus’ spike protein that set off alarm bells when it was later found in strains in the United Kingdom, South Africa and Brazil.
The Boston patient is now being viewed as an important harbinger of the coronavirus’ ability to spin off new and more dangerous versions of itself. Though he died over the summer, the medical file he left behind is helping experts anticipate the emergence of new strains by focusing on the role of a growing population of patients with compromised immune systems who battle the virus for months.
Among the sickest of C19 patients, this population of “long haulers” appears to play a key role in incubating new variants of the coronavirus, some of which could change the trajectory of the pandemic.
The mutations that arose from this single patient are “a microcosm of the viral evolution we’re seeing globally,” said Dr. Jonathan Z. Li, an infectious-disease specialist at Brigham and Women’s Hospital in Boston who treated him. “He showed us what could happen” when a germ with a knack for genetic shape-shifting stumbles upon conditions that reward it for doing so.
Indeed, situations in which patients can’t clear a viral infection are “the worst possible scenario for developing mutations,” said Dr. Bruce Walker, an immunologist and founding director of the Ragon Institute in Boston.
As weeks of illness turn into months, a virus copies itself millions of times. Each copy is an opportunity to make random mistakes. As it spins off new mutations, the virus may happen upon ones that help it resist medications, evade the immune system and come back stronger.
C19 patients were just beginning to fill the beds of Brigham and Women’s Hospital in the spring of 2020, when the Boston patient was first admitted. He had a fever, nausea, and a CT of his lungs that bore the hallmark “ground glass” appearance of the new disease, said Li, who was part of a team that detailed the man’s case in the New England Journal of Medicine.
But C19 was just one of his challenges. For 22 years, he suffered from a rare disorder called antiphospholipid syndrome, which caused his immune system to attack his own organs and spawn dangerous blood clots throughout his body.
To keep his rogue immune system from killing him, the patient required an arsenal of immunosuppressive drugs. But in his fight against the coronavirus, those medicines kept the patient’s punching arm tied behind his back.
The Boston patient tested positive for SARS-CoV2 infections four separate times over 22 weeks. He was admitted to the hospital six times, including stints in intensive care. Doctors treated him with three courses of the antiviral medication remdesivir and once with Regeneron’s experimental cocktail of monoclonal antibodies.
Swabs taken from his nose and throat during his second hospital stay provided the first hint of the virus’ startling pace of genetic transformation: Compared with a sample taken during his first hospitalization, 11 letters in the coronavirus’ 30,000-letter sequence had flipped, and nine such nucleotides had dropped out.
His next trip to the hospital landed him in the ICU. Tests revealed that 10 more letters in the virus’ genetic code had changed and that one more had been deleted in a period of just five weeks. Three weeks later, after he had seemed to recover, he tested positive again and was put on a mechanical ventilator to help him breathe. This time, researchers found 11 more letter changes and 24 more deletions in the virus’ genome.
Scientists couldn’t say whether the Boston patient was failing to kick the virus or whether it was changing so completely that his immune system couldn’t recognize it.
One thing was clear: More than half of the alterations occurred in a stretch of genetic code that dictates the structure of the virus’ spike protein, the protuberance that latches onto human cells and initiates an infection. The virus’ “receptor binding domain” — essentially the key that picks the lock on a human cell — accounts for only 2% of the virus’ genetic code. But 38% of the mutations spun off during the Boston patient’s prolonged illness were concentrated in just that spot.
In late December, British scientists speculated that just such a scenario involving an immunocompromised patient somewhere in England may have spawned the mutations that distinguish the U.K. strain.
Walker said he fears there are many more such patients out there, including people with untreated HIV infections. Immunocompromised by HIV, sick with C19 and given drugs that reward SARS-CoV-2 for devising “escape” mutations, such people could become crucibles of viral mutation.
Scientists in South Africa share that anxiety.
“In South Africa, the country with the world’s biggest HIV epidemic, one concern has been the prolonged viral replication and intra-host evolution in the context of HIV infection,” wrote the authors of a preliminary study that alerted the world to the new variant in early December.
So far, there’s no evidence that patients with HIV are more prone to long-lasting cases of C19. And even if they were, a lengthy chain of immunocompromised patients probably would have been necessary to generate the numerous mutations that distinguish the South Africa strain, its discoverers said.
Scientists are still trying to understand how certain mutations like N501Y have cropped up in so many places at once. Has the mushrooming scale of the pandemic given the virus too many opportunities to alter itself? Or are these mutations arising in a small number of people, like the Boston patient, and then somehow hitching a ride around the world?
Both factors are probably at work, and the longer and hotter the pandemic rages, the more chances the virus will have to devise random mutations.
The Boston patient shows why that can be so dangerous. In his case, the stretches of genetic code that were most prone to change affected structures that C19 vaccines and drugs are designed to recognize. Now there are hints that the changes could undermine the value of those remedies.
Tulio de Oliveira, an infectious-disease researcher at South Africa’s University of KwaZulu-Natal, sees a pattern in which uncontrolled spread and long-haul infections work in tandem to fuel coronavirus mutations.
Many of the places where new variants have been identified — including South Africa, Britain and California — experienced two waves of outbreaks divided by just a few months. That, De Oliveira suspects, is no mere coincidence.
In the first wave, he said, the proliferation of infections gives the virus ample opportunity to take on genetic changes that may live on in bodies of immunocompromised patients. By the time a second wave begins, novel variants that were incubating in these long-haulers have also begun to circulate. When they encounter vast numbers of new hosts, the result is a fertile environment for strains to establish themselves — if their genetic modifications confer some advantage.
The best way to prevent the emergence of more mutations is to both expand vaccinations and do more to protect people with compromised immune systems, De Oliveira said.
“If we keep the virus around for a long time, we will be giving it more opportunities to outsmart us,” he said.

Source: https://www.latimes.com/science/story/2021-01-30/long-term-covid-19-patients-are-incubating-dangerous-new-coronavirus-strains

4. Schizophrenia increases risk of dying from C19

People with schizophrenia have an almost three times greater risk of dying from C19 than people without the mental disorder, a new study finds, even after accounting for higher rates of heart disease, diabetes, and smoking. Schizophrenia ranks second — after age — in the odds of dying after C19 infection.
People with mood or anxiety disorders had no increased risk of death from coronavirus infection in the cohort study of more than 7,300 patients treated in New York last spring.
Researchers in the field previously thought underlying conditions were to blame because people with schizophrenia, on average, die 15 years earlier than those without the disorder. Now the authors wonder if genetic variation in immune response might be at fault. Click on the link below to read the study.

Source: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2775179

H. The Road Back?

1. More Freedom Is the Whole Point of Vaccines

When Americans began receiving coronavirus vaccines last month, people started fantasizing about the first thing they’d do when the pandemic ends: go back to work, visit family, hug friends. But the public discussion soon shifted.
One news article after another warned about everything that could go wrong: Protection isn’t immediate; vaccinated people can still transmit the virus; vaccinated people might get mild infections that could become chronic; vaccines might not work as well against new coronavirus variants.
“COVID-19 Vaccine Doesn’t Mean You Can Party Like It’s 1999,” one headline admonished. Can vaccinated people at least hang out with one another? Nope, masks and distancing are still required. “Bottom line,” another article concluded ominously: “You will need to wear a face mask after you’re vaccinated until C19 cases become nearly nonexistent.”
Although scientists are still learning about how much the two government-approved vaccines reduce transmission of the coronavirus, the evidence shows that their efficacy against disease is phenomenal. Although not zero-risk, close contact between two people is safer if one has received a vaccine, and safer still if both are vaccinated.
For this reason, public-health experts elsewhere in the world are emphasizing hope. In a new social-media campaign, health officials from across the European Union stress that vaccination will help people get their lives back. “I’ll do it to protect my father and organise a big family weekend get-together,” declares Belgium’s chief scientific adviser. “I did it because I want us to live normally again,” says the chief coronavirus adviser in Romania.
But in the United States, the prevailing message is that, because vaccines aren’t perfect, people who have received them shouldn’t let down their guard in any way—not even at gatherings with just a few other vaccinated people. “Based on science and how vaccines work, it certainly is likely that [such a gathering] will end up being lower-risk,” a pharmacologist from Johns Hopkins University told The Washington Post. “But right now, we just don’t know.”
Government officials are no more upbeat. In response to the question of whether a vaccinated person needs to continue taking precautions, the CDC states that “not enough information is currently available” to say when—or even if—it will stop recommending the use of masks and distancing.
The message that vaccines aren’t 100 percent effective in preventing disease, and that the data are still out on how much they reduce transmission, is an accurate and important one. Risk-mitigation strategies are needed in public spaces, particularly indoors, until more people are vaccinated and infections wane.
But not all human interactions take place in public. Advising people that they must do nothing differently after vaccination—not even in the privacy of their homes—creates the misimpression that vaccines offer little benefit at all. Vaccines provide a true reduction of risk, not a false sense of security. And trying to eliminate even the lowest-risk changes in behavior both underestimates people’s need to be close to one another and discourages the very thing that will get everyone out of this mess: vaccine uptake.
From the beginning, many government officials and media commentators have made a habit of blaming the pandemic on the public’s misbehavior. Concerns that vaccinated people will start throwing “rona raves” or exhibit other irresponsible behavior therefore come as no surprise.
But people are likely to behave far more cautiously. Survey data from Great Britain suggest that a large majority of people there plan to continue following public-health guidelines after vaccination—albeit, for some, less strictly. Nearly a third of epidemiologists who responded to a New York Times survey late last year said they would be comfortable returning to more activities of daily life after vaccination, but these are likely to be baby steps, not leaps.
Maybe a grandparent will decide to hold a grandchild for the first time in a year. Maybe people will send their kids back to school, fly to visit aging loved ones, socialize with a few other vaccinated friends, try to go on a date or two. Even if those decisions are unlikely to cause harm, they appear selfish if the goal is to eliminate the tiniest risk of spreading the coronavirus. But health is more than the absence of disease.
The question of how vaccines change people’s individual and collective risk-benefit calculus has implications beyond whether vaccinated adults can have drinks together inside one of their homes. It also affects decisions about how crucial parts of society will function: whether unvaccinated children can go back to school after teachers are vaccinated, or whether an unvaccinated person can visit a vaccinated elderly relative in a nursing home. Those discussions suffer when experts and other commentators belabor the potential pitfalls of vaccines out of fear that some people will abuse their freedom.
The vaccines are poised to deliver what people so desperately want: an end, however protracted, to this pandemic. Everyone’s focus needs to be on getting the highest-risk people vaccinated as quickly as possible, not on faulting vaccinated people for a few unmasked hugs.

Source: https://www.theatlantic.com/ideas/archive/2021/01/giving-people-more-freedom-whole-point-vaccines/617829/

I. Back to School!?

1. C19 Spread Appears Limited in Schools When Precautions Followed

The spread of C19 appears to be limited within schools when masking and other safety precautions are implemented, according to a report from the Centers for Disease Control and Prevention released on Tuesday.
Health officials looked at C19 transmission in K-12 schools in Wood County, Wis., which suggested that “schools might be able to safely open with appropriate mitigation efforts in place,” according to the CDC report summary.
The schools had a number of mitigation measures in place, the report said, including an estimated masking compliance of more than 92% among students. Class sizes ranged from 11 to 20 students, and different cohorts of students rarely interacted. Staff members were told to wear masks and keep 6 feet away from others.
Among the 5,530 students and staff members across 17 schools, a total of 191 C19 cases were reported from Aug. 31 through Nov. 29. Based on individual case investigations, only seven cases, or 3.7%, were attributed to in-school transmission, all of which were students.
Meanwhile, between 7% and 40% of tests in the surrounding communities were coming back positive.
“Attending school where recommended mitigation strategies are implemented might not place children in a higher risk environment than exists in the community,” the report said. “In-person schooling for children has numerous health and societal benefits, especially for children and parents of lower socioeconomic status.”
Three researchers at the CDC also published an editorial in the Journal of the American Medical Association on Tuesday, saying there is growing data showing there is “a path forward” to return to full in-person instruction for schools, if communities take steps to reduce transmission and limit other activities such as indoor sports practice.
The editorial called for universal face mask use in schools and improving ventilation and screening testing, among other measures. Staff and students should continue to have online options, especially for those at an increased risk of severe illness or death from C19, the editorial said.
“Ultimately the decision whether a particular school opens or stays open is up to the school and local community,” a CDC spokesman said in a statement. “Kids need to be and should be in school for many reasons provided schools can strictly adhere to recommended guidelines to prevent transmission in school settings.”
A second report published by the CDC on Tuesday found that the virus spread during two high-school wrestling tournaments in Florida in early December. Following the tournaments, at least 38 attendees, or roughly 30%, ended up testing positive for the virus, and the virus spread to 41 close contacts. One contact, an adult over 50 years old, died. All winter indoor and outdoor high-school athletics in the county were suspended.
Physical distancing isn’t feasible for sports such as wrestling, the report noted, and the American Academy of Pediatrics has recommended against wearing masks during wrestling because of the choking hazard.
“High-contact school athletic activities for which mask wearing and physical distancing are not possible should be postponed during periods with substantial or high levels of SARS-CoV-2 community transmission,” the report said.

Source: https://www.wsj.com/articles/covid-19-spread-appears-limited-in-schools-when-safety-precautions-followed-cdc-says-11611697861

J. Innovation & Technology

1. New Biosensors Quickly Detect C19 Coronavirus Proteins and Antibodies

Scientists have created a new way to detect the proteins that make up the pandemic coronavirus, as well as antibodies against it. They designed protein-based biosensors that glow when mixed with components of the virus or specific C19 antibodies. This breakthrough could enable faster and more widespread testing in the near future. The research appears in Nature.
To diagnose coronavirus infection today, most medical laboratories rely on a technique called RT-PCR, which amplifies genetic material from the virus so that it can be seen. This technique requires specialized staff and equipment. It also consumes lab supplies that are now in high demand all over the world. Supply-chain shortfalls have slowed C19 test results in the United States and beyond.
In an effort to directly detect coronavirus in patient samples without the need for genetic amplification, a team of researchers led by David Baker, professor of biochemistry and director of the Institute for Protein Design at UW Medicine, used computers to design new biosensors. These protein-based devices recognize specific molecules on the surface of the virus, bind to them, then emit light through a biochemical reaction.
Antibody testing can reveal whether a person has had C19 in the past. It is being used to track the spread of the pandemic, but it too requires complex laboratory supplies and equipment.
The same team of UW researchers also created biosensors that glow when mixed with C19 antibodies. They showed that these sensors do not react to other antibodies that might also be in the blood, including those that target other viruses. This sensitivity is important for avoiding false-positive test results.
“We have shown in the lab that these new sensors can readily detect virus proteins or antibodies in simulated nasal fluid or donated serum, said Baker. “Our next goal is to ensure they can be used reliably in a diagnostic setting. This work illustrates the power of de novo protein design to create molecular devices from scratch with new and useful functions.”
Beyond C19, the team also showed that similar biosensors could be designed to detect medically relevant human proteins such as Her2 (a biomarker and therapy target for some forms of breast cancer) and Bcl-2 (which has clinical significance in lymphoma and some other cancers), as well as a bacterial toxin and antibodies that target Hepatitis B virus.

Source: https://scitechdaily.com/new-biosensors-quickly-detect-covid-19-coronavirus-proteins-and-antibodies/

K. Projections & Our (Possible) Future

1. Global analysis suggests C19 is seasonal

With cities around the globe locking down yet again amid soaring C19 numbers, could seasonality be partially to blame? New research from the University of Illinois says yes.
In a paper published in Evolutionary Bioinformatics, Illinois researchers show C19 cases and mortality rates, among other epidemiological metrics, are significantly correlated with temperature and latitude across 221 countries.
“One conclusion is that the disease may be seasonal, like the flu. This is very relevant to what we should expect from now on after the vaccine controls these first waves of C19,” says Gustavo Caetano-Anollés, professor in the Department of Crop Sciences, affiliate of the Carl R. Woese Institute for Genomic Biology at Illinois, and senior author on the paper.
The seasonal nature of viral diseases is so widespread that it has become part of the English vernacular. For example, we often speak of the “flu season” to describe the higher incidence of influenza during the cold winter months. Early in the pandemic, researchers and public health officials suggested SARS-CoV-2 may behave like other coronaviruses, many of which rear their heads in fall and winter. But data was lacking, especially on the global scale. The work of Caetano-Anollés and his students fills that specific knowledge gap.
First, the researchers downloaded relevant epidemiological data (disease incidence, mortality, recovery cases, active cases, testing rate, and hospitalization) from 221 countries, along with their latitude, longitude, and average temperature. They pulled the data from April 15, 2020, because that date represents the moment in a given year in which seasonal temperature variation is at its maximum across the globe. That date also coincided with a time during the early pandemic when C19 infections were peaking everywhere.
The research team then used statistical methods to test if epidemiological variables were correlated with temperature, latitude, and longitude. The expectation was that warmer countries closer to the equator would be the least affected by the disease.
“Indeed, our worldwide epidemiological analysis showed a statistically significant correlation between temperature and incidence, mortality, recovery cases, and active cases. The same tendency was found with latitude, but not with longitude, as we expected,” Caetano-Anollés says.
While temperature and latitude were unmistakably correlated with C19 cases, the researchers are quick to point out climate is only one factor driving seasonal C19 incidence worldwide.
They accounted for other factors by standardizing raw epidemiological data into disease rates per capita and by assigning each country a risk index reflecting public health preparedness and incidence of co-morbidities in the population. The idea was that if the disease was surging in countries with inadequate resources or higher-than-average rates of diabetes, obesity, or old age, the risk index would appear more important in the analysis than temperature. But that wasn’t the case. The risk index did not correlate with the disease metrics at all.
Earlier work from Caetano-Anollés and his coworkers identified areas in the SARS-CoV-2 virus genome undergoing rapid mutation, some represented in the new virus variant out of Britain, and other genomic regions becoming more stable. Since similar viruses show seasonal upticks in mutation rates, the research team looked for connections between mutational changes in the virus and temperature, latitude, and longitude of the sites from which genomes were sampled worldwide.
“Our results suggest the virus is changing at its own pace, and mutations are affected by factors other than temperature or latitude. We don’t know exactly what those factors are, but we can now say seasonal effects are independent of the genetic makeup of the virus,” Caetano-Anollés says.
Caetano-Anollés notes more research is needed to explain the role of climate and seasonality in C19 incidences, but he suggests the impact of policy, such as mask mandates, and cultural factors, such as the expectation to look out for others, are key players as well. However, he doesn’t discount the importance of understanding seasonality in battling the virus.
The researchers say our own immune systems could be partially responsible for the pattern of seasonality. For example, our immune response to the flu can be influenced by temperature and nutritional status, including vitamin D, a crucial player in our immune defenses. With lower sun exposure during the winter, we don’t make enough of Vitamin D. But it’s too soon to say how seasonality and our immune systems interact in the case of C19.
“We know the flu is seasonal, and that we get a break during the summer. That gives us a chance to build the flu vaccine for the following fall,” Caetano-Anollés says. “When we are still in the midst of a raging pandemic, that break is nonexistent. Perhaps learning how to boost our immune system could help combat the disease as we struggle to catch up with the ever-changing coronavirus.”

Source: https://www.eurekalert.org/pub_releases/2021-01/uoic-gas012721.php

2. New C19 projection forecasts more than 650,000 deaths by May 1

The latest C19 forecasts from the Institute for Health Metrics and Evaluation at the University of Washington now incorporate two new virus variants.
In a worst-case scenario, with widespread transmission of the B.1.351 variant first detected in South Africa and mobility returning to pre-pandemic levels in the vaccinated, the US is predicted to see approximately 654,000 total deaths by May 1 and a resurgence of the virus in the spring in some states, including California and Florida, rather than a continued decline. Keeping mobility low and maintaining social distancing could reduce that number by approximately 30,000.
“What we’re seeing is sobering, and will require us to continue taking this pandemic very seriously,” said Christopher Murray, director of IHME. “Getting vaccines out quickly is essential, and masks are still one of the best tools we have to keep transmission low and avoid the worst possible outcome. People will need to continue taking precautions even once they are vaccinated, because of the potential for more contagious variants to spread.”
All scenarios in the new forecasts include vaccine distribution and the presence of the B.1.1.7 C19 variant where it is currently detected. Without transmission of B.1.351, the forecast in the US drops to 595,000 deaths by May 1, an increase of about 26,000 from last week’s predictions. This increase is driven by taking into account that some states are not re-imposing social distancing mandates even when daily death rates are high.
Instead of assuming that decision-makers will re-impose social distancing mandates when deaths reach a threshold of 8 per million, all scenarios now assume – in line with several months of observations – that if mandates are not imposed promptly at that point, they will not be imposed until deaths reach 15 per million.
“We have not been seeing governments taking action to apply cautionary measures as quickly as expected, and have incorporated that information into the modeling,” said Murray. “Without measures to control the spread of the disease, mobility remains higher and transmission is more likely.”
Herd immunity is unlikely to be a factor in slowing transmission in the coming months, even with vaccination campaigns ramping up. Higher levels of immunity are needed with a more contagious variant and during the winter months, and vaccine hesitancy is an obstacle to achieving herd immunity. As important is the fact that we do not know if the vaccines work to block infection even though they prevent severe disease – IHME’s model currently assumes, based on limited data, that vaccines’ effectiveness in blocking infection is only 50% of their effectiveness in preventing severe disease.
In the United States, approximately 25% of people have indicated they would reject a vaccine and another 25% are unsure. IHME’s forecasts predict only 38% of people in the US will be immune by May 1.
In a worst-case scenario, there is also the possibility of a third wave next winter. “Governments and the public need to plan for the real prospect that C19 must be managed on an ongoing basis,” Murray said. “It’s critical to vaccinate as many people as possible and to prepare for long-term behavior change. It’s likely that wearing masks and taking other measures to prevent transmission, especially in the winter months, will become an ongoing part of our lives.”
IHME’s projections are based on an epidemiological model that includes data on cases, deaths, and antibody prevalence, as well as location-specific C19 testing rates, vaccination rollout, mobility, social distancing mandates, mask use, population density and age structure, and pneumonia seasonality, which shows a strong correlation with the trajectory of C19.

Source: https://www.eurekalert.org/pub_releases/2021-01/ifhm-ncf012821.php

3. Temperature, Humidity & Wind Predict Second Wave of C19 Pandemic

Transmission rates of the coronavirus vary in the northern and southern hemispheres depending on the time of year, pointing to a weather dependence.

The “second wave” of the coronavirus pandemic has placed much blame on a lack of appropriate safety measures. However, due to the impacts of weather, research suggests two outbreaks per year during a pandemic are inevitable.
Though face masks, travel restrictions, and social distancing guidelines help slow the number of new infections in the short term, the lack of climate effects incorporated into epidemiological models presents a glaring hole that can cause long-term effects. In Physics of Fluids, from AIP Publishing, Talib Dbouk and Dimitris Drikakis, from the University of Nicosia in Cyprus, discuss the impacts of these parameters.
Typical models for predicting the behavior of an epidemic contain only two basic parameters, transmission rate and recovery rate. These rates tend to be treated as constants, but Dbouk and Drikakis said this is not actually the case.
Temperature, relative humidity, and wind speed all play a significant role, so the researchers aimed to modify typical models to account for these climate conditions. They call their new weather-dependent variable the Airborne Infection Rate index.
When they applied the AIR index to models of Paris, New York City, and Rio de Janeiro, they found it accurately predicted the timing of the second outbreak in each city, suggesting two outbreaks per year is a natural, weather-dependent phenomenon. Further, the behavior of the virus in Rio de Janeiro was markedly different from the behavior of the virus in Paris and New York, due to seasonal variations in the northern and southern hemispheres, consistent with real data.
The authors emphasize the importance of accounting for these seasonal variations when designing safety measures.
“We propose that epidemiological models must incorporate climate effects through the AIR index,” said Drikakis. “National lockdowns or large-scale lockdowns should not be based on short-term prediction models that exclude the effects of weather seasonality.”
“In pandemics, where massive and effective vaccination is not available, the government planning should be longer-term by considering weather effects and design the public health and safety guidelines accordingly,” said Dbouk. “This could help avoid reactive responses in terms of strict lockdowns that adversely affect all aspects of life and the global economy.”
As temperatures rise and humidity falls, Drikakis and Dbouk expect another improvement in infection numbers, though they note that mask and distancing guidelines should continue to be followed with the appropriate weather-based modifications.

Source: https://scitechdaily.com/temperature-humidity-wind-predict-second-wave-of-covid-19-pandemic/

L. Practical Tips & Other Useful Information

1. Air Purifiers Can Actually Increase the Spread of Airborne Viruses Like C19

The positions of air inlets and outlets in confined spaces, such as elevators, greatly affect airborne virus transmission. In Physics of Fluids, by AIP Publishing, researchers from University of Nicosia in Cyprus show while air purifiers would be expected to help, they may actually increase the spread.
Air quality in small spaces can quickly degrade without ventilation. However, adding ventilation will increase the rate at which air, possibly laden with viruses, can circulate in the small space. Elevator manufacturers have added air purifiers to take care of this problem, but the systems have not been designed to account for their effect on overall air circulation.
Air purifiers use ultraviolet radiation to kill viruses and other microbes, but they also circulate air, sucking it in and exhausting cleaned air. This adds to overall circulation, an aspect that has not been considered in previous research.

Installing an air purifier inside an elevator alters the air circulation significantly but does not eliminate airborne transmission. In contrast, an air purifier may increase the droplet spread because the air intake integrated inside the purifier equipment induces flow circulation that can add to the transport of contaminated saliva droplets in the cabin.

Previous work from the scientists indicated droplets of saliva can travel 18 feet in five seconds when an unmasked person coughs. The authors extended the same model to examine the effects of face masks and weather conditions.
Investigators carried out calculations for a 3D space equivalent to an elevator capable of holding five people. A mild cough was simulated at one position in the space, and air inlets and outlets were added in various locations to study their influence on circulation. An air purifier was also included in the simulation.
“We quantified the effect of air circulation on airborne virus transmission and showed that installing an air purifier inside an elevator alters the air circulation significantly but does not eliminate airborne transmission,” said author Dimitris Drikakis.
The investigators found the risk of airborne virus transmission is lowest for low ventilation rates.
“This is due to reduced flow mixing inside the elevator,” said author Talib Dbouk. “Regulatory authorities should thus define the minimum ventilation required depending on the type of building.”
The study looked at the role of an air purifier, considering only the air intake and exhaust associated with the purifier, but not the mechanism inside the purifier that kills the virus. Even with an air purifier in place, airborne virus transmission is still significant.
“Our results show that installing an air purifier may increase the droplet spread,” Drikakis said. “The air intake integrated inside the purifier equipment induces flow circulation that can add to the transport of contaminated saliva droplets in the cabin.”
The observed effect increases with the number of infected persons in the elevator. Restricting the number of people allowed in an elevator would minimize the spread of the virus as would better design of air purifier and ventilation systems.

Source: https://scitechdaily.com/air-purifiers-can-actually-increase-the-spread-of-airborne-viruses-like-covid-19/

2. How to Get a C19 Vaccine: a State-by-State Guide

The CDC has issued recommendations for who should get the vaccines first, but states established their own criteria. Most prioritized health-care workers and long-term-care residents first; now, many have moved on to those over 65 or 75 years of age and people with health conditions that put them at high risk.
While states have set the priorities for inoculations, many have pushed the responsibility for administering them onto individual hospitals, clinics and local public health agencies.
Each state has divided their populations into groups or phases or tiers, and each is working through them at its own pace. Most states’ websites acknowledge the limited vaccine supply, and that many of the hotlines are likely to be experiencing difficulties. Residents are encouraged to keep trying and to check the websites regularly for updates. Some states give residents hotline numbers for direct help with vaccines and appointment scheduling; some offer the option to pre-register for the vaccine even if they aren’t eligible yet, and will notify those people when it’s their turn to schedule an appointment.
The states also request residents don’t go to a clinic or provider without an appointment.
The WSJ has information and links to the appropriate state websites. Click on the link here to find more information about your state.

Source: https://www.wsj.com/articles/how-to-get-a-covid-19-vaccine-a-state-by-state-guide-11611703769

M. Johns Hopkins COVID-19 Update

February 2, 2021

1. Cases & Trends

Overview

The WHO C19 Dashboard reports 102.94 million cases and 2.23 million deaths as of 11am EST on February 2. The weekly global incidence decreased for the third consecutive week, down to 3.63 million new cases. This is a decrease of nearly 15% compared to the previous week, and it is the lowest weekly total since late October. Weekly global mortality also decreased nearly 4% compared to the previous week, down to 93,803 deaths. Considering the reporting interruptions over the winter holidays, it is unclear exactly when the actual global incidence peaked; however, the decrease in mortality could be an early indication of a longer-term trend corresponding to decreases in incidence starting 2-4 weeks ago.
Our World in Data reports that 101.31 million vaccine doses have been administered globally, a 48% increase since this time last week.

United States

The US CDC reported 26.03 million total cases and 439,955 deaths. The US is currently averaging 3,145 deaths per day, and it could surpass 450,000 cumulative deaths in the next 3-4 days.
National-level daily incidence continues to decrease, down from nearly 250,000 new cases in per day in mid-January to around 150,000. While the daily incidence continues to decrease, the current average is still more than double the peak of the summer surge. Daily mortality is also beginning to show signs of declining. The US has reported decreasing daily mortality for 5 consecutive days, down 5% since January 26. Additional data are needed to determine if this is an early indication of a longer-term trend, but a decrease spanning multiple days is an encouraging sign.
The Johns Hopkins CSSE dashboard reported 26.35 million US cases and 444,336 deaths as of 1:30pm EST on February 2.

2. RUSSIAN VACCINE

Sputnik V, Russia’s primary vaccine candidate, appears to be safe and effective in preventing symptomatic C19, based on preliminary analysis of Phase 3 clinical trial data published in The Lancet. The clinical trials included nearly 20,000 participants, with 75% randomly assigned to receive the vaccine. The researchers identified 16 cases of C19 among the treatment group (14,964 participants) and 62 cases among the placebo group (4,902), corresponding to an overall efficacy of 91.6% in terms of preventing C19 disease, similar to the results for the Pfizer-BioNTech and Moderna vaccines. Notably, the vaccine also exhibited 91.8% efficacy among adults over the age of 60, and no moderate or severe cases of C19 were reported among the vaccinated participants. No serious adverse events were determined to be associated with the vaccine.
The Sputnik V vaccine is administered in 2 doses, administered 21 days apart. It requires the temperature to be maintained at approximately 0°F (-18°C), with short-term storage at 36-46°F (2-8°C). In contrast, ultra-cold storage (approximately -80°F or -62°C) is required for the Pfizer-BioNTech vaccine.
The Russian government came under criticism in August 2020 after making the Sputnik V vaccine candidate available to the public before Phase 3 clinical trials were completed. More than a dozen other countries have already authorized the use of the Sputnik V vaccine.

3. US VACCINATION

The US CDC C19 Response Team published data from the early stages of SARS-CoV-2 vaccination efforts in the US. The first study, published in the CDC’s MMWR, described demographic characteristics among those vaccinated in the first month—December 14, 2020 to January 14, 2021. The researchers analyzed age, sex, and race/ethnicity data for nearly 13 million individuals who received at least 1 dose of the vaccine. The majority of those vaccinated were older adults, with 55% aged 50 years and older, including 13.4% aged 65-74 years and 15.6% aged 75 years and older. Additionally, 63% of those vaccinated were female.
Among 6.7 million individuals with race/ethnicity data, the majority (60.4%) were White*, compared to 11.5% Hispanic/Latinx, 5.4% Black*, 6.0% Asian*, and 2.3% American Indian, Alaskan Native, Native Hawaiian, or Other Pacific Islander* and 14.4% were listed as Multiple races/ethnicities or Other. The researchers indicate that the demographic distributions appear to largely reflect those of the earliest priority populations outlined by the CDC’s Advisory Committee on Immunization Practices, including LTCF residents and healthcare workers. Notably, however, the proportion of Black vaccinees was lower than would be expected considering the racial/ethnic distribution these priority groups.
The second article, also published in the CDC’s MMWR, discussed vaccination coverage among LTCF residents and staff. The researchers evaluated data on nearly 1.3 million individuals vaccinated through the CDC Pharmacy Partnership for Long-Term Care Program from December 18, 2020 to January 17, 2021. Among these individuals, 713,909 were residents and 582,104 were facility staff. In total 12,702 facilities participated in the program, of which 11,460 (90.2%) conducted at least one on-site vaccination clinic. This effort provided at least 1 dose of the vaccine to an estimated 77.8% of residents at these facilities, but only 37.5% of staff. Due to a combination of factors—including age, underlying health conditions, and prolonged close contact in congregate settings—LTCF residents are at elevated risk for infection, severe disease, and death, so it is important to achieve high vaccination coverage at these facilities.
In addition to state and local governments, tribal nations are also scaling up vaccination efforts. The Navajo Nation, one of the most severely affected tribal nations during the US epidemic (29,860 cases), eased its weekend curfew in an effort to expand vaccination. The principal challenges are addressing vaccine hesitancy, particularly among older adults who are at elevated risk, and reaching individuals who live in rural areas that are unable or unwilling to travel to get vaccinated, especially during adverse winter weather conditions. Proactive effort by tribal leadership and health workers has driven substantial progress in terms of vaccination coverage. To date, Navajo Nation has administered at least 1 dose of SARS-CoV-2 vaccine to more than 20% of its population, higher coverage than any US state or territory.

4. VACCINATION PROTESTS

Dodger Stadium in Los Angeles, California, is currently serving as one of the largest mass vaccination sites in the US, but protests by anti-vaccination groups caused the site to be temporarily shut down on Saturday when protesters blocked the entrance to the stadium. Fortunately, the disruption did not result in the cancellation of any appointments, but Governor Gavin Newsom emphasized that protests will not be deterred by protests. Protesters reportedly attempted to intimidate individuals waiting in line and spread misinformation about C19 and the vaccine. New safety measures at Dodger Stadium will clearly delineate where protesters are permitted to be in order to prevent further disruptions to vaccination operations.

5. GERMANY

On January 29, the European Commission issued a conditional marketing authorization (CMA) for the use of the AstraZeneca-Oxford University SARS-CoV-2 vaccine in adults aged 18 and older. While the announcement acknowledged that the clinical trials primarily included adults aged 18-55 years, the CMA did not include an upper age limit. In a decision stemming from a concern about insufficient efficacy data in older adults, Germany authorized the AstraZeneca-Oxford vaccine only for adults aged 18-64. Currently, vaccine eligibility in Germany is limited to residents and staff of long-term care facilities, adults aged 80 years and older, and frontline healthcare workers. Because the AstraZeneca-Oxford vaccine is not authorized for many high-risk individuals due to Germany’s age restrictions, Germany will reportedly review its eligible populations and prioritize use of that particular vaccine in younger healthcare workers and LTCF staff.
Germany has struggled with a slow start to its vaccination campaign, and Chancellor Angela Merkel reportedly met with state governors, EU leadership, and representatives from the pharmaceutical industry yesterday to identify mechanisms to speed progress toward national vaccination coverage. Following the meeting, Chancellor Merkel indicated that Germany still anticipates being able to vaccinate its entire population by September 2021, even if no additional vaccines are authorized for use.
Like many countries around the world, Germany recently instituted travel restrictions in response to emerging, highly transmissible SARS-CoV-2 variants. Notably, non-German citizens arriving from “areas of variant of concern”—currently Brazil, Eswatini, Ireland, Lesotho, Portugal, South Africa, and the UK—will not be permitted to enter the country, even with a recent negative SARS-CoV-2 test. Individuals who are eligible to enter—including German citizens and residents—and recent travel to “high incidence areas” or “virus variant areas” must provide proof of a negative test prior to entry, and all individuals with recent travel to “risk areas”—which covers most countries, including most in Europe—must be tested within 48 hours after arrival. All travelers arriving from places identified as at risk, high-incidence, or variant areas are required to self-quarantine for 10 days after they arrive. The quarantine can potentially be terminated after 5 days, with a negative test. The new restrictions are expected to remain in place through at least February 17.

6. DRC DRONE VACCINE DISTRIBUTION

Drones have previously been used for the delivery of medical supplies, including vaccines, to areas that are remote or difficult to access. The Democratic Republic of the Congo (DRC) recently announced a partnership between VillageReach, Swoop Aero, and the DRC Ministry of Health—“Drones for Health”—will use drone to promote equitable access to healthcare for half a million people in remote communities of the Equateur province. In addition to standard medical supplies, the new program is expected to support SARS-CoV-2 vaccination efforts in the country. These drones will be used to deliver medicine and other supplies to 75 health facilities in the province.

7. REFUGEES & DISPLACED POPULATIONS

Refugees are among the most vulnerable populations in the world, particularly in the midst of a pandemic. Being displaced from their homes and separated from community support systems, refugees and other displaced populations often live in congregate settings without access to clean water or proper sanitary equipment, which exacerbates risk of transmission and severe disease. Furthermore, displaced populations face significant barriers in terms of accessing healthcare, and medical organizations that work with these populations are often underfunded and overwhelmed. King Abdullah II Ibn Al Hussein of Jordan recently announced that the Jordanian government initiated vaccination operations for refugee population in the country. King Abdullah viewed it as part of Jordan’s “global responsibility” and “moral duty” to protect the most vulnerable from C19. The UN Refugee Agency (UNHCR) applauded Jordan’s initiative to include displaced populations in its vaccination program and encouraged other countries to follow Jordan’s example.
In recognition of the disproportionate C19 burden among immigrant populations, many of whom are racial and ethnic minorities, the US Department of Homeland Security (DHS) is committing resources to ensure equal access to SARS-CoV-2 vaccines for undocumented immigrants. A statement issued by DHS emphasized the “public health imperative” in ensuring access to vaccination, regardless of immigration status. While many undocumented immigrants are not refugees, they may face similar stigma and barriers to accessing public health and healthcare. As part of this effort, the Federal Emergency Management Agency will coordinate vaccination clinics that aim to reach “underserved and rural communities,” and federal immigration officials, including Immigration and Customs Enforcement and Customs and Border Protection, “will not conduct enforcement operations at or near vaccine distribution sites or clinics” in order to encourage participation by vulnerable individuals and communities.

8. PREGNANT WOMEN

On January 26, the WHO updated its guidance on the Moderna SARS-CoV-2 vaccine to include pregnant women. Previously, the WHO recommended against vaccinating pregnant women unless they were at elevated risk, which conflicted with recommendations published by the US CDC. While the current iterations of both sets of guidelines do not explicitly recommend vaccinating pregnant women, both note that there is currently no evidence to suggest that the vaccine poses safety concerns for pregnant women.
A study published in JAMA: Pediatrics provides evidence that pregnant women may be able to pass IgG antibodies against SARS-CoV-2 to their fetus. The study involved 1,417 women who recently gave birth. Among 83 mothers with detectable SARS-CoV-2 antibodies, 72 (86.7%) transferred IgG antibodies to their fetus—as detected in the newborns’ cord blood. IgM antibodies were not detected in any cord blood specimens, and antibodies were not detected in any infants born to mothers without detectable antibodies. The concentration of antibodies in the cord blood was significantly correlated with the concentration in the mother, but the antibodies were successfully transferred by mothers who exhibited symptomatic disease and asymptomatic infection. The study did not explicitly evaluate the ability to transfer antibodies developed as a result of vaccination; however, the researchers indicate that the results align with similar studies on transplacental transfer of vaccine-conferred antibodies for other diseases. Further research is necessary to determine the recommended timing for vaccination of pregnant women in order to achieve sufficient transplacental transfer of SARS-CoV-2 antibodies to the fetus.

9. US ECONOMIC STIMULUS

With the Democratic party now in control of the US House of Representatives, Senate, and White House, pressure is increasing to negotiate additional federal economic relief for the C19 epidemic. US President Joe Biden announced his proposal for a new C19 economic stimulus and recovery package, the American Rescue Plan, which includes US$1.9 trillion in funding. The package includes support for SARS-CoV-2 testing and vaccination efforts ($415 million) and small businesses ($440 million). It also includes $1 trillion in direct support for individuals and families, including another round of stimulus checks and increased and extended unemployment benefits. Additionally, the package includes broader provisions to increase the federal minimum wage and expand access to affordable childcare and healthcare.
While the Democratic party holds a majority in the Senate (with the tie-breaking vote from Vice President Kamala Harris), there are limited options available to pass a funding bill without some degree of Republican support. In hopes of stimulating bipartisan negotiations, 10 Republican Senators visited the White House to outline an alternate funding package, which totals $618 billion. The Republican proposal would include smaller and more targeted direct stimulus checks for individuals; maintain the current $300 federal supplemental unemployment benefits through June, as opposed to $400 through September in the White House plan; and reduce support for schools from $170 billion in the White House plan to $20 billion. The Republican plan would also eliminate funding to expand the national public health workforce; $350 billion in support to state, local, and tribal governments; subsidies for health insurance premiums; and the minimum wage increase. The initial meeting was reportedly productive, and there appears to be interest on both sides to continue negotiations.
As we have covered previously, the large-scale response efforts in many jurisdictions—including testing, surveillance, and vaccination—have posed major financial challenges to jurisdictions across the country. An investigation by STAT News found that senior US government officials under the Trump Administration “actively lobbied Congress to deny state governments any extra funding for the C19 vaccine rollout.” STAT News reports that the primary point of contention reportedly dealt with the speed with which states were using previous federal funding allocations for C19 response.

10. VACCINE DEVELOPMENT & TESTING

Clover Biopharmaceuticals, a Chinese company developing a SARS-CoV-2 vaccine candidate, announced that it is moving forward with Phase 2/3 clinical trials for its candidate SARS-CoV-2 vaccine using an adjuvant manufactured by Dynavax, rather than one produced by GlaxoSmithKline (GSK). According to a press release from Clover, the two adjuvants induced similar immune response in Phase 1 clinical trials, but Clover selected the Dynavax adjuvant for its forthcoming Phase 2/3 clinical trials due to concerns about production capacity for the GSK product. Clover anticipates vaccine production capacity of “hundreds of millions of doses in 2021” and ultimately as high as 1 billion doses per year. Clover expects to have preliminary data available from the Phase 2/3 trials by the middle of 2021.