Recent Developments & Information
January 5, 2021
South African variant of coronavirus is different than the UK variant, and vaccines may be less effective against the South African mutation. (See stories below for more details)
“As data on the new variant coronavirus roll in, there is cause for real concern.”Zeynep Tufekci, The Atlantic
“The South African variant has a number of additional mutations, including changes to some of the virus’ spike protein which are concerning.”Dr Simon Clarke, an expert in cell microbiology at the University of Reading
“My concern, as a virologist, is that if you wanted to make a vaccine-resistant strain, what you would do is to build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection. You are essentially maximizing the opportunity for the virus to learn about the human immune system. Learn about antibodies. Learn how to evade them.”Paul Bieniasz, a retrovirologist at Rockefeller University, who expressed concern over the UK’s strategy to partially vaccinate people so that more can be vaccinated quickly
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.
- Cases & Tests
- Top 5 States in Cases, Deaths, Hospitalizations & Positivity
- U.S. Covid-19 Hospitalizations Hit Record
- The Virus Is Still Winning And There Is Cause for Real Concern (!)
- What we do and don’t know about new C19 mutations (!) (*)
- South Africa coronavirus variant: What is the risk? (!)
- Alcohol can reduce effectiveness of C19 vaccine (!) (*)
- C19 Vaccines Focus on the Spike Protein – But Here’s Another Target (!)
- New research may explain severe virus attacks on the lungs
- As Rollout Falters, Scientists Debate New Vaccination Tactics (!) ©
- Allergists offer reassurance regarding potential allergic reactions to C19 vaccines (!) (*)
- Britain takes a gamble with C19 vaccines, upping the stakes for the rest of us (!)
- The vaccine blame game
- Cheap hair lice drug may cut risk of C19 death by 80% (!)
- Drug used to treat cancer ‘could cure C19’ (!)
- ‘Natural compounds’ could kill C19 spike protein
- 3 surprising drugs being repurposed to fight C19
- New Strategy Identifies Existing Drug That Inhibits Coronavirus – Outperforms Remdesivir
- NIH Researchers Uncover Brain Damage in C19 Patients, Despite No Infection of the Brain
- Loss of Smell and Taste May Affect Nutrition and Mental Health (*)
- New MIT Model Could Help Determine Quarantine Measures Needed to Reduce C19’s Spread
- How Does New York Keep Transit Riders Safe From C19? Trial & Error.
- Children are wearing masks up to 4.5 hours per day. What effect is this having on their health? (*)
- Children much more likely to asymptomatic than adults
- Some Masks Can Be Worse Than Not Wearing One at All (*) (!) ©
- Six Ways to ‘Reboot Your Brain’ After a Hard Year of C19 (*)
L. Linked Stories
- Here’s Why Distribution of the Vaccine Is Taking Longer Than Expected
- Pharmaceutical Scientist Warns of Potential Problems With Remdesivir As C19 Treatment
- Scientists Develop System for Visualizing Breath to Provide Insights Into C19 Transmission
- ‘Still waiting for my turn’: Primary care doctors are being left behind in the vaccine rollout
- Tracking C19 in transmission in Chicago schools: Public health officials take data-driven approach to reopening city public schools With good mitigation, in-school transmission risk appears lower than outside school
- Coronavirus Stigma Lingers Long After Disease Fades
- How modelling C19 has changed the way we think about epidemics
- A quirk of C19 tests can track the new coronavirus variant
- C19 Pandemic Likely Improved Your Commute to Work
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A. Pandemic Headlines
(In no particular order)
- 94.1% Efficacy Shown in Moderna COVID-19 Vaccine Trial
- Feds may cut Moderna vaccine doses in half so more people get shots, Warp Speed adviser says
- The F.D.A. opposes halving Moderna vaccine doses
- Biggest Vaccination Effort in U.S. History, yet Some States May Lack Facilities for Administering COVID-19 Vaccine to Residents
- Dr. Fauci Says Mandatory COVID Vaccines Are “On The Table”, Especially For Travel, School
- Alarming number of US health care workers are refusing COVID-19 vaccine
- New data shows intensive care units filling up across the U.S.
- Mexico approved the Oxford-AstraZeneca vaccine for emergency use
- India defends the decision to approve a homegrown vaccine before trials finish
- NY Assemblyman Defends Bill Permitting Detainment Of Carriers Of “Contagious Disease”
- South African COVID variant poses greater risk than UK strain
- COVID-19 vaccine’s effect on South African strain still unknown
- Ex-FDA boss predicts new COVID strain will ‘grow quickly’ in US
- The highly contagious strain of the coronavirus found in New York and California
- One in four doctors attacked, harassed on social media (!)
- NYC only vaccinated 2,617 people in first 2 days of 2021, more than 8 million to go
- ‘Blithering incompetence’: Critics pan NY’s COVID vaccine rollout
- NY Gov. Cuomo blames NYC Mayor de Blasio, hospitals for slow COVID-19 vaccine rollout
- Cuomo Threatens To Fine Hospitals For Not Meeting COVID Vaccination Targets
- Use them or lose them, Florida’s governor warns hospitals about vaccine supplies
- LA EMS workers told not to transport patients with ‘little chance of survival’
- California city to remove public seating as coronavirus cases spike
- California endures more hospitalizations and deaths after its post-holiday infection surgeEx-FEMA honcho blasts vaccine rollout, nursing home deaths
- Operation Warp Speed advisor says vaccine rollout ‘needs to improve’
- New York’s total coronavirus cases exceed 1,000,000
- Tennessee vaccine administrators gave doses to family, friends hours after turning away at-risk citizens
- Second California hospital busted for giving COVID-19 vaccine to relatives
- California Funeral Homes Run Out of Space as COVID-19 Rages
- A pharmacist at a Wisconsin hospital, an “admitted conspiracy theorist,” destroyed 500 doses of coronavirus vaccine because he thought they weren’t safe, police said
- 900,000 excess deaths expected over next 15 years from pandemic rise in unemployment
- Prime Minister Boris Johnson closed schools and declared a strict national lockdown in England in an attempt to contain a more contagious variant
- India approved a locally made vaccine, as well as one made by Oxford-AstraZeneca, for emergency use
- Putin Pushes Plan To Roll Out COVID “Immunity Passports” In Russia
- Top US Official Says ‘Growing Body Of Evidence’ Shows COVID-19 Leaked From Chinese Lab
- England goes back into national lockdown amid another COVID-19 surge
- Britain reimposes a strict lockdown as hospitalizations are up 30% from last week
- British Prime Minister Johnson: Stricter Lockdown Restrictions Likely on the Way
- UK reports 50,000+ cases for 7th day
- UK starts Astra-Zeneca vaccine rollout
- UK reopens field hospitals as COVID-19 cases surge
- US begins 2nd doses
- UK to delay second vaccine doses
- In Europe, more countries delay second vaccine doses or mull plans to do so
- London to close all elementary schools amid COVID surge, new strain
- Japan expected to declare second emergency for Tokyo area
- Germany Leads Europe Into New Wave Of Lockdowns As COVID Numbers Surge
- Greece announced 1-week lockdown
- Thou shall not comply: Greek Church tells priests to defy COVID lockdown orders
- Norway imposes new restrictions to halt third COVID-19 wave
- South Korea widens ban on private gatherings
- Norway imposes new restrictions
- Thailand sees 745 new cases Monday
- Scotland to enter another national lockdown
- In Somalia, COVID-19 vaccines are distant as virus spreads
- Americans have fled their local lockdowns for Mexico City, where coronavirus restrictions have been more relaxed. But hospitals in the Mexican capital are overwhelmed, and cases of Covid-19 are surging
- NYC teachers worry about school safety as COVID-19 cases spike
- Virus cases in U.S. jails and prisons surpass 500,000
- Pope Francis criticized people who traveled abroad to sidestep pandemic lockdowns, saying they were ignoring those who were suffering
- Struggling substance-abuse centers are shutting down or relying on virtual programming. People who struggle with dependence have started relapsing
- The NCAA intends to hold its men’s basketball tournament entirely in Indiana in an effort to limit the spread of the coronavirus
- Israel has distributed the first of two doses to more than 10% of its population, in an unusually successful vaccination campaign
- Amid Erectile Dysfunction Fears, India Claims COVID Vaccine Is “110% Safe”
- As post-holiday infections surge, Lebanon gears for lockdown
- Real estate moguls allegedly help rich pals jump COVID vaccine line
- Rich New Yorkers pony up $400 or more for COVID-test house calls
- Breadlines Stretch Across America: This Economic Collapse Is Much Worse Than You Are Being Told
- The surging virus prompts a call to halt in-person TV and film production
- Flu cases down 99.5% from this point last year
- Marriage rates have declined dramatically since onset of pandemic
- Life’s a breach: Sandals Caribbean resorts in hot water over COVID violations
- Disney opens ‘park-hopping’ despite new COVID-19 strain found in Florida
- Police struggle to keep skiers off slopes in Germany amid COVID lockdown
- French police shut down illegal rave that drew over 2,500 people
- Florida beach and bar parties rage on amid alarming surge in COVID-19 cases
- 2020 taught us one good thing: Celebrities are meaningless
- South Koreans scramble to arrange cosmetic surgery before mask-wearing ends
- California college offering students COVID-19 tests inside vending machines
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) the number of cases and deaths reported during the holidays may below actual numbers due to delays in reporting, which could result in subsequent reports being higher than actual numbers as the reporting catches up.
1. Cases & Tests
- Total Cases = 86,095,596
- New Cases (7 day average) = 622,932
- Record high number of new cases (753,595) was reported on 12/31
- After declining from 12/21 to 12/29, the 7 day average of new cases has been rising at a rapid rate
- Total Cases = 21,353,051
- New Cases (7 day average) = 218,967
- Percentage of New Global Cases (7 day average) = 35.2%
- After declining from 12/17 to 12/28, the 7 day average of new cases have been rapidly increasing
- US percentage of new global cases is very high
- Total Deaths = 1,859,886
- New Deaths (7 day average) = 11,105
- Record high number of new deaths (15,123) occurred on 12/30
- After declining from 12/22 to 11/28, the 7 day average has been increasing
- US percentage of new global deaths is high
- Total Deaths = 362,123
- New Deaths (7 day average) = 2,702
- Percentage of Global New Deaths = 24.3%
- Record high number of new deaths (3,876) occurred on 12/30
- After declining from 12/23 to 12/27, the 7 day average of new deaths have been rapidly increasing
3. Top 5 States in Cases, Deaths, Hospitalizations, Patients in ICU & Positivity (1/5)
- After reaching 12.6% on 12/27, the US Positivity Rate climbed for the 8th consecutive day to 16.7% on 1/4. We expect the rate to continue climbing following New Year’s.
- Overall, 45 states reported higher positivity rates over the last seven days (+12 states since 12/29).
- IN leads the US with an average of 48.1% of all tests resulting positive
- Eleven states: 7-day positivity rates greater than 40%. (+6 since 12/29)
- Nine states: 7-day positivity rates greater than 30%. (+1 since 12/29)
- Seven states: 7-day positivity rates greater than 20%. (-4 since 12/29)
- One state (OR): 7-day positivity rates less than 5%. (-2 since 12/29)
- In total, 49 states have 7-day positivity rates greater than 5% (+2 since 12/29)
- Hospitalizations in the US reached an all-time high of 128,210, up 5.9% since a week ago. Hospitalizations are up 26.7% over the last 30 days and are expected to continue increasing due to the holidays.
- Fourteen states have had increases of hospitalized patients of more than 10% in the past week. (+2 since 12/29)
- CA hospitalizations reached an all-time high of 22,003 (+6.6% since 12/28)
- 30 states have more than 1,000 hospitalized patients (-unch since 12/29)
- 22 states saw decreases in the number of hospitalized patients over the past week. (-6 since 12/29)
- ICU Patients in the US reached an all-time high of 23,435 up 3.7% since a week ago. The number of ICU patients are up 17.5% over the last 30 days and are expected to continue increasing due to the holidays.
- Six states have seen the number of ICU patients increase by more than 10% since a week ago (unch since 12/29)
- 30 states have more than 100 patients in ICU, (-unch since 12/29)
- 22 states saw decreases in the number of ICU patients over the past week (-3 since 12/29).
4. U.S. Covid-19 Hospitalizations Hit Record
What to Know
- New York reported its first case of a highly contagious new C19 strain.
- Travel over the holidays set a new pandemic record, as some experts warn gatherings could lead to a new surge in cases.
- U.S. hospitalizations were at a record-high 125,544 Sunday. Newly reported U.S. cases exceeded 210,000.
- Thousands more workers are needed to meet this year’s big vaccine production push.
Key US Trends
- The number of newly reported C19 cases in the U.S. was down from a day earlier, but the number hospitalized with the disease hit a record.
- The nation reported more than 210,000 new cases for Sunday, according to data compiled by Johns Hopkins University. That was down from the previous day’s reported 297,491, which included data backlogs from states that didn’t report numbers for New Year’s Day. The holiday may still be affecting some reporting.
- As of Saturday, the seven-day moving average of newly reported cases was 205,093, according to a Wall Street Journal analysis of Johns Hopkins data, topping 200,000 for the first time since Christmas Day. The 14-day average was 197,321. When the seven-day average exceeds the 14-day average, it suggests cases are on the rise.
- Hospitalizations in the U.S. hit a record 125,544 on Sunday—exceeding 125,000 for the fourth time in five days—according to the Covid Tracking Project, with 23,231 people in intensive care. Hospitals in hard-hit areas have run short of beds, and nurses and doctors find themselves overwhelmed.
- Federal officials on Sunday acknowledged that the rollout of the coronavirus vaccine in 2020 was disappointing, but predicted the pace will quicken and could soon surpass 1 million shots a day.
C. New Variants of Coronavirus
1. The Virus Is Still Winning And There Is Cause for Real Concern
- This simple chart shows why the new variants of the coronavirus — first detected in Britain and South Africa — are so worrisome.
- The above chart compares the spread of the virus in each of those two countries with the spread in a group of nearby countries. As you can see, cases have surged in Britain and South Africa since the variants first surfaced — while holding fairly steady in the rest of western Europe and southern Africa.
- The new variants may not be the only reason. Britain and South Africa differ from their neighbors in other ways, as well. But there is no obvious explanation for the contrast besides the virus’s mutations.
- This suggests the rest of the world may now be at risk of a new C19 surge.
- The variants already seem to have spread around much of the world. More than 30 other countries, including the U.S., have diagnosed cases with the variant first detected in Britain, which is known as B.1.1.7. Scientists say that it could soon become the dominant form of the virus.
- The B.1.1.7 variant appears to be between 10% and 60% more transmissible than the original version. One possible reason: It may increase the amount of the virus that infected people carry in their noses and throats (the viral load), which in turn would raise the likelihood that they infect others through breathing, talking, sneezing, coughing and so on.
- As I’ve explained before, the biggest factor that will determine how many more people die from the virus isn’t likely to be the precise effectiveness of the vaccines or even the speed of their rollout. The biggest factor is instead likely to be how much we reduce the spread of the virus over the next few months, through a combination of mask wearing, social distancing and expanded testing. Those efforts can cut caseloads — and, by extension, deaths — more rapidly than a mass vaccination campaign can.
- But the U.S. was struggling to hold down new infections even before the variants appeared, and they will probably make the job more difficult. “I dismissed the news initially because viruses mutate all the time and there have been too many baseless ‘mutant-ninja virus’ doomsaying headlines this year,” Zeynep Tufekci wrote in The Atlantic last week. “However, as data on the new variant roll in, there is cause for real concern.”
2. What we do and don’t know about new C19 mutations
- The emergence in Britain and South Africa of two new variants of the coronavirus (SARS-CoV-2), which are potentially far more infectious versions of the virus, has prompted widespread concern. Here is what we know—and what we don’t—about the mutations.
What are they?
- Scientists have tracked multiple mutations of SARS-CoV-2 since it appeared in China in late 2019. The vast majority of mutations did not materially alter either the virus’s virulence or transmissibility.
- However, one mutation—variant B.1.1.7, which likely emerged in southeastern England in September, according to Imperial College London—has now been detected in countries across the world, including the US, France and India.
- Another variant, 501.V2, was detected in South Africa in October, and has since spread to several nations, including Britain and France. Read more about the South Afrianc variant here (https://www.bbc.com/news/health-55534727)
- Both have multiple mutations to the virus, most notably on its spike protein—the part of the virus that latches on to human cells and helps it spread.
- Specifically, the mutated versions have an altered receptor binding domain known as N501Y, which is situated on the virus’ protein spike and which allows easier access to the ACE2 receptor in human cells.
- This makes the mutated versions potentially more infectious than other strains.
Are they more contagious?
- Indeed, several recent studies— yet to be peer-reviewed—have concluded that the British variant of SARS-CoV-2 is likely to be far more transmissible than other strains.
- The NERVTAG expert committee which advises the British government on disease control has estimated the new mutation (B.1.1.7) is between 50% and 70% more transmissible.
- Last week researchers at Imperial College London released the results of a study into thousands of genetic sequences of SARS-CoV-2 found in Britain between October and December.
- They found that the new variant had a “substantial transmission advantage”, with a reproduction rate between 0.4 and 0.7 higher than the unmutated virus.
- Preliminary studies on the South African variant have also concluded it is more contagious than regular SARS-CoV-2.
- Although initial data seems to confirm that the two new versions are more contagious, experts have urged caution.
Are they more dangerous?
- There is currently no evidence to suggest that the mutated viruses are any stronger than normal.
- But increased transmissibility alone poses an enormous problem, given that a small but consistent percentage of C19 patients require hospital care.
- “Increased transmissibility eventually translates to a far higher incidence rate, and even with the same mortality, this means significant pressure on health systems,” said Coignard.
- Adam Kucharski, an epidemiologist at LSHTM, said that a virus that is 50 percent more contagious would be a “much bigger problem” than one that is 50 percent more deadly.
- In a Twitter thread, he explained how a disease such as C19, with a reproduction (R) rate of 1.1—where each patient on average infects 1.1 others—and a mortality rate of 0.8 percent would be expected to produce 129 deaths within a month.
- If the mortality rate increased 50 percent, the number of deaths would rise to 193.
- But due to the exponential growth in cases with a more contagious variant, a disease with a 50% higher transmission rate would see the death toll hit 978.
- Arnaud Fontanet, an epidemiologist with France’s science council, admitted on Monday that the new British variant was “extremely concerning right now”.
- Initial studies also concluded that the British variant was significantly more contagious among young people, which raises the issue of whether or not to keep schools open.
- The LSHTM study concluded that lockdowns similar to those seen across Britain in November would be insufficient to stem the new variant’s spread “unless primary schools, secondary schools, and universities are also closed”.
Will vaccines still work?
- As vaccination campaigns get underway across the world, is there any reason to fear that the new mutations may not respond to the host of vaccines already on the market?
- After all, the messenger RNA vaccines developed by Pfizer and Moderna trick the body into reproducing the virus’s spike protein—the precise part of the pathogen that has mutated in the new versions.
- The ECDC said it was too soon to know if the mutations will impact vaccine efficacy.
- Last week Henry Walke from the American Centers for Disease Control told reporters that “experts believe our current vaccines will be effective against these strains”.
- On Monday however, Francois Balloux, professor of Computational Systems Biology and Director at University College London’s Genetics Institute said that the South African variant’s spike protein mutation “helps the virus to bypass immune protection provided by prior infection or vaccination”.
- German vaccine developer BioNTech has said that if needed it could develop a new vaccine that would work on mutated versions within six weeks.
What can we do about them?
- Coignard said it was impossible to eradicate the new viral variants entirely, although the goal from policymakers should be “maximum delay” of their spread.
- The ECDC says that in countries currently unaffected by the new mutations, “efforts to delay the spread should mirror those made during the earlier stage of the pandemic”.
- These include tests and quarantining of new arrivals, contact tracing and limited travel, it said.
- By sheer luck, certain existing PCR tests can detect the British variant.
- Fontanet therefore advocated “extremely aggressive surveillance” through widespread testing.
- “We need to be even more vigilant in our prevention measures to slow the spread of C19 by wearing masks, staying at least six feet apart from people we don’t live with, avoiding crowds, ventilating indoor spaces and washing our hands,” said Walke.
3. South Africa coronavirus variant: What is the risk?
- A new variant of coronavirus circulating in South Africa is now being seen in other countries.
- Experts are urgently studying it to understand what risk it poses.
- The South African variant is called 501.V2.
What do experts say?
- The South African variant carries a mutation called E484K.
- It’s different to another recently discovered variant that scientists have been studying in the UK.
- Both the new South African and UK ‘Kent’ variants appear to be more contagious, which is a problem because tougher restrictions on society may be needed to control the spread.
- While changes in the new UK variant are unlikely to harm the effectiveness of current vaccines, there is a chance those in the South African variant may do so to some extent, say scientists.
- It is too soon to say for sure, or by how much, until more tests are completed, although it is extremely unlikely the mutations would render vaccines useless.
- Dr Simon Clarke, who is an expert in cell microbiology at the University of Reading, said: “The South African variant has a number of additional mutations including changes to some of the virus’ spike protein which are concerning.”
- The spike protein is what coronavirus uses to gain entry into human cells. It is also the bit that vaccines are designed around, which is why experts are worried about these particular mutations.
- “They cause more extensive alteration of the spike protein than the changes in the UK (“Kent”) variant and may make the virus less susceptible to the immune response triggered by the vaccines,” said Dr Clarke.
- Prof Francois Balloon from University College London, said: “The E484K mutation has been shown to reduce antibody recognition. As such, it helps the virus SARS-CoV-2 to bypass immune protection provided by prior infection or vaccination.”
- But even in the worst case scenario, vaccines can be redesigned and tweaked to be a better match in a matter or weeks or months, if necessary, say experts.
Is it more dangerous?
- There is currently no evidence to suggest that any of the mutated viruses cause more serious illness.
How far has it spread?
- It is already the dominant virus variant in the Eastern and Western Cape provinces of South Africa.
- Other countries including Austria, Norway and Japan, have also found cases.
D. New Scientific Findings & Research
1. Alcohol can reduce effectiveness of C19 vaccine
- Drinking alcohol can reduce the effectiveness of C19 vaccines, according to UK experts.
- They found that even three glasses of Prosecco halved the levels of white blood cells like lymphocytes that are crucial in creating antibodies to attack viruses, the report said.
- “You need to have your immune system working tip-top to have a good response to the vaccine, so if you’re drinking the night before, or shortly afterward, that’s not going to help,” University of Manchester professor Sheena Cruickshank told the paper.
- Cruickshank advised people to avoid drinking in the days around getting vaccinated.
- Meanwhile, in vodka-loving Russia, officials have been even stricter — telling citizens to avoid booze for two months after getting jabbed.
3. C19 Vaccines Focus on the Spike Protein – But Here’s Another Target
- The spike protein is the focus of most C19 vaccines as it is the part of the virus that enables it to enter our cells. Virus replication only happens inside cells, so blocking entry prevents more virus being made. If a person has antibodies that can recognize the spike protein, this should stop the virus in its tracks.
- The three most advanced vaccines (from Oxford/AstraZeneca, Pfizer/BioNTech and Moderna) all work by getting our own cells to make copies of the virus spike protein. The Oxford vaccine achieves this by introducing the spike protein gene via a harmless adenovirus vector. The other two vaccines deliver the spike protein gene directly as mRNA wrapped in a nanoparticle. When our own cells make the spike protein, our immune response will recognize it as foreign and start making antibodies and T cells that specifically target it.
- However, the coronavirus (SARS-CoV-2) is more complicated than just a spike protein. There are, in fact, four different proteins that form the overall structure of the virus particle: spike, envelope (E), membrane (M) and nucleocapsid (N). In a natural infection, our immune system recognizes all of these proteins to varying degrees. So how important are immune responses to these different proteins, and does it matter that the first vaccines will not replicate these?
Parts of the coronavirus, including the N protein.
- Following SARS-CoV-2 infection, researchers have discovered that we actually make the most antibodies to the N protein – not the spike protein. This is the same for many different viruses that also have N proteins. But how N protein antibodies protect us from infection has been a long-standing mystery. This is because N protein is only found inside the virus particle, wrapped around the RNA. Therefore, N protein antibodies cannot block virus entry, will not be measured in neutralization assays that test for this in the lab, and so have largely been overlooked.
New mechanism discovered
- Our latest work from the MRC Laboratory of Molecular Biology in Cambridge has revealed a new mechanism for how N protein antibodies can protect against viral disease. We have studied another virus containing an N protein called lymphocytic choriomeningitis virus and shown a surprising role for an unusual antibody receptor called TRIM21.
- Whereas antibodies are typically thought to only work outside of cells, TRIM21 is only found inside cells. We have shown that N protein antibodies that get inside cells are recognized by TRIM21, which then shreds the associated N protein. Tiny fragments of N protein are then displayed on the surface of infected cells. T cells recognize these fragments, identify cells as infected, then kill the cell and consequently any virus.
- We expect that this newly identified role for N protein antibodies in protecting against virus infection is important for SARS-CoV-2, and work is ongoing to explore this further. This suggests that vaccines that induce N protein antibodies, as well as spike antibodies, could be valuable, as they would stimulate another way by which our immune response can eliminate SARS-CoV-2.
- Adding N protein to SARS-CoV-2 vaccines could also be useful because N protein is very similar between different coronaviruses – much more so than the spike protein. This means it’s possible that a protective immune response against SARS-CoV-2 N protein could also offer some protection against other related coronaviruses, such as MERS.
- Another potential benefit that may arise from including N protein in SARS-CoV-2 vaccines is due to the low mutation rates seen in the N protein sequence. Some changes to the sequence of SARS-CoV-2 have been reported over the course of this pandemic, with the most significant changes occurring in the spike protein. There is some concern that if the spike sequence alters too much, then new vaccines will be required. This could be similar to the current need for annual updating of influenza vaccines. However, as the N protein sequence is much more stable than the spike, vaccines that include a component targeting the N protein are likely to be effective for longer.
3. New research may explain severe virus attacks on the lungs
- In some cases, immune cells in the lungs can contribute to worsening a virus attack. In a new study, researchers at Karolinska Institutet in Sweden describe how immune cells called macrophages develop in the lungs and which of them may be behind severe lung diseases. The study, which was published in Immunity, may contribute to future treatments for C19, among other diseases.
- The structure of the lungs exposes them to viruses and bacteria from both the air and the blood. Macrophages are immune cells that, among other things, protect the lungs from such attacks. But under certain conditions, lung macrophages can also contribute to severe lung diseases such as chronic obstructive pulmonary disease (COPD) and C19.
- Macrophages can have different origins and develop, among other things, from white blood cells, monocytes, that are divided into genetically determined main types. In humans, two of these are “classical” CD14+ monocytes and “non-classical” CD16+ monocytes.
- In a new study at Karolinska Institutet, researchers have used a model to study the development of lung macrophages directly in a living lung. They combined the model with RNA sequencing, a method to study gene activity in individual cells, and thereby discovered how blood monocytes become human lung macrophages.
- “In our study, we show that classical monocytes migrate into airways and lung tissue and are converted into macrophages that protect the health and function of the lungs. We have also identified a special kind of monocyte, HLA-DRhi, which is an intermediate immune cell between a blood monocyte and an airway macrophage. These HLA-DRhi monocytes can leave the blood circulation and migrate into the lung tissue,” says Tim Willinger, Associate Professor at the Department of Medicine, Huddinge, Karolinska Institutet, who led the study.
- The nonclassical monocytes, however, develop into macrophages in the many blood vessels of the lungs and do not migrate into the lung tissue.
- “Certain macrophages in the lungs probably have a connection to a number of severe lung diseases. In respiratory infections, for example, monocytes in the lungs develop into macrophages, which combat viruses and bacteria. But a certain type of macrophage may also contribute to severe inflammation and infections,” says the study’s first author Elza Evren, a doctoral student in Tim Willinger’s research team.
- In an infection with the novel coronavirus, SARS-COV-2, which causes C19, researchers believe that protective, anti-inflammatory macrophages are replaced by pro-inflammatory lung macrophages from blood monocytes.
- “The existence of these blood monocyte-derived macrophages has been shown in other studies to correlate with how severely ill a person becomes in C19 and how extensive the damage to the lungs is. Patients with severe C19 also have fewer HLA-DRhi monocytes in their blood, probably because they move away from the blood into the lungs. Given their important role in rapid inflammatory responses, our results indicate that future treatments should focus on inflammatory macrophages and monocytes to reduce lung damage and mortality from severe C19,” says Tim Willinger.
E. Vaccines & Testing
1. As Rollout Falters, Scientists Debate New Vaccination Tactics
- As governments around the world rush to vaccinate their citizens against the surging coronavirus, scientists are locked in a heated debate over a surprising question: Is it wisest to hold back the second doses everyone will need, or to give as many people as possible an inoculation now — and push back the second doses until later?
- Since even the first shot appears to provide some protection against C19, some experts believe that the shortest route to containing the virus is to disseminate the initial injections as widely as possible now.
- Officials in Britain have already elected to delay second doses of vaccines made by the pharmaceutical companies AstraZeneca and Pfizer as a way of more widely distributing the partial protection afforded by a single shot.
- Health officials in the United States have been adamantly opposed to the idea. “I would not be in favor of that,” Dr. Anthony S. Fauci, the nation’s top infectious disease expert, told CNN on Friday. “We’re going to keep doing what we’re doing.”
- But on Sunday, Moncef Slaoui, scientific adviser of Operation Warp Speed, the federal effort to accelerate vaccine development and distribution, offered up an intriguing alternative: giving some Americans two half-doses of the Moderna vaccine, a way to possibly milk more immunity from the nation’s limited vaccine supply.
- The rising debate reflects nationwide frustration that so few Americans have gotten the first doses — far below the number the administration had hoped would be inoculated by the end of 2020. But the controversy itself carries risks in a country where health measures have been politicized and many remain hesitant to take the vaccine.
- “Even the appearance of tinkering has negatives, in terms of people having trust in the process,” said Natalie Dean, a biostatistician at the University of Florida.
- The public rollout remained bumpy over the weekend. Seniors lined up early for vaccinations in one Tennessee town, but the doses were gone by 10 a.m. In Houston, the Health Department phone system crashed on Saturday, the first day officials opened a free vaccination clinic to the public.
- Nursing home workers in Ohio were opting out of the vaccination in great numbers, according to Gov. Mike DeWine, while Mayor Eric Garcetti of Los Angeles, now a center of the pandemic, warned that vaccine distribution was moving far too slowly. Hospitalizations of C19 patients during the past month have more than doubled in California.
- The vaccines authorized so far in the United States are produced by Pfizer-BioNTech and Moderna. Britain has greenlit the Pfizer-BioNTech and Oxford-AstraZeneca vaccines.
- All of them are intended to be delivered in multiple doses on a strict schedule, relying on a tiered protection strategy. The first injection teaches the immune system to recognize a new pathogen by showing it a harmless version of some of the virus’s most salient features.
- After the body has had time to study up on this material, as it were, a second shot presents these features again, helping immune cells commit the lesson to memory. These subsequent doses are intended to increase the potency and durability of immunity.
- Clinical trials run by Pfizer-BioNTech and Moderna showed the vaccines were highly effective at preventing cases of C19 when delivered in two doses separated by three or four weeks.
- Some protection appears to kick in after the first shot of vaccine, although it’s unclear how quickly it might wane. Still, some experts now argue that spreading vaccines more thinly across a population by concentrating on first doses might save more lives than making sure half as many individuals receive both doses on schedule.
- That would be a remarkable departure from the original plan. Since the vaccine rollout began last month in the United States, second shots of the vaccines have been held back to guarantee that they will be available on schedule for people who have already gotten their first injections.
- But in Britain, doctors have been told to postpone appointments for second doses that had been scheduled for January, so that those doses can be given instead as first shots to other patients. Officials are now pushing the second doses of both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines as far back as 12 weeks after the first one.
- In a regulatory document, British health officials said that AstraZeneca’s vaccine was 73% effective in clinical trial participants three weeks after the first dose was given and before the second dose was administered. (In cases in which participants never received a second dose, the interval ended 12 weeks after the first dose was given.)
- But some researchers fear the delayed-dose approach could prove disastrous, particularly in the United States, where vaccine rollouts are already stymied by logistical hurdles and a patchwork approach to prioritizing who gets the first jabs.
- “We have an issue with distribution, not the number of doses,” said Saad Omer, a vaccine expert at Yale University. “Doubling the number of doses doesn’t double your capacity to give doses.”
- Federal health officials said last week that some 14 million doses of the Pfizer-BioNTech and Moderna vaccines had been shipped out across the country. But as of Saturday morning, just 4.2 million people in the United States had gotten their first shots.
- That number is most likely an underestimate because of lags in reporting. Still, the figure falls far short of the goal that federal health officials set as recently as last month to give 20 million people their first shots by the end of 2020.
- Many of these rollout woes are caused by logistical issues — against the backdrop of a strained health care system and skepticism around vaccines. Freeing up more doses for first injections won’t solve problems like those, some researchers argue.
- Shweta Bansal, a mathematical biologist at Georgetown University, and others also raised concerns about the social and psychological impacts of delaying second doses.
- “The longer the duration between doses, the more likely people are to forget to come back,” she said. “Or people may not remember which vaccine that they got, and we don’t know what a mix and match might do.”
- In an emailed statement, Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, endorsed only the strictly scheduled two-dose regimens that were tested in clinical trials of the vaccines.
- The “depth or duration of protection after a single dose of vaccine,” he said, can’t be determined from the research published so far. “Though it is quite a reasonable question to study a single-dose regimen in future clinical trials, we simply don’t currently have these data.”
- Dr. Slaoui of Operation Warp Speed said in an emailed statement on Sunday that “the approach some countries are taking of delaying the booster shot could backfire and could decrease confidence in the vaccines.”
- The vaccine makers themselves have taken divergent positions.
- In a trial of the Oxford-AstraZeneca vaccine, volunteers in Britain were originally intended to receive two doses given four weeks apart. But some vaccinated participants ended up receiving their doses several months apart, and still acquired some protection against C19.
- An extended gap between doses “gives you a lot of flexibility for how you administer your vaccines, dependent on the supply that you have,” said Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca.
- Delayed dosing could help get countries “in very good shape for immunizing large swaths of their populations to protect them quickly.”
- Steven Danehy, a spokesman for Pfizer, struck a far more conservative tone. “Although partial protection from the vaccine appears to begin as early as 12 days after the first dose, two doses of the vaccine are required to provide the maximum protection against the disease, a vaccine efficacy of 95%,” he said.
- “There are no data to demonstrate that protection after the first dose is sustained after 21 days,” he added.
- There is no dispute that second doses should be administered sometime near the first dose. “They key is to expose the immune system at a time when it still recognizes” the immunity-stimulating ingredients in the vaccine, said Angela Rasmussen, a virologist affiliated with Georgetown University.
- During a public health emergency, “companies will tend to pick the shortest period they can that gives them that full, protective response,” said Dr. Dean of the University of Florida.
- But it’s unclear when that critical window really starts to close in the body. Akiko Iwasaki, an immunologist at Yale University who supports delaying second doses, said she thought the body’s memory of the first injection could last at least a few months.
- Doses of other routine vaccines, she noted, are scheduled several months apart or even longer, to great success. “Let’s vaccinate as many people as possible now, and give them the booster dose when they become available,” she said.
- Dr. Robert Wachter, chair of the department of medicine at the University of California, San Francisco, said he was originally skeptical of the idea of delaying second doses.
- But the disappointingly slow vaccine rollout in the United States, coupled with concerns about a new and fast-spreading variant of the coronavirus, have changed his mind, and he now believes this is a strategy worth exploring.
- “The past couple weeks have been sobering,” he said.
- Other researchers are less eager to take the gamble. Delaying doses without strong supporting data “is like going into the Wild West,” said Dr. Phyllis Tien, an infectious disease physician at the University of California, San Francisco. “I think we need to follow what the evidence says: two shots 21 days apart for Pfizer, or 28 days apart for Moderna.”
- Some experts also fear that delaying an immunity-boosting second dose might give the coronavirus more opportunity to multiply and mutate in partly protected people.
- There is some evidence to support the alternative strategy of halving the dose of each shot, suggested on Sunday by Mr. Slauoi of Operation Warp Speed.
- In an interview on the CBS program “Face the Nation,” Dr. Slaoui pointed to data from clinical trials run by Moderna, whose vaccine is typically given in two doses, four weeks apart, each containing 100 micrograms of active ingredient.
- In the trials, people between the ages of 18 and 55 who received two half-doses produced an “identical immune response to the 100 microgram dose,” Dr. Slaoui said. The F.D.A. and Moderna are now considering implementing this regimen on a more widespread scale, he added.
- While there’s little or no data to support the soundness of delayed dose delays, Dr. Slaoui said, “injecting half the volume” might constitute “a more responsible approach that will be based on facts and data to immunize more people.”
- But Dr. Dean and John Moore, a vaccine expert at Cornell University, both pointed out that this regimen would still represent a departure from the ones rigorously tested in clinical trials.
- A half-dose that elicits an immune response that appears similar to that triggered by a full dose may not in the end deliver the expected protection against the coronavirus, Dr. Moore noted. Halving doses “is not something I would want to see done unless it were absolutely necessary,” he said.
- “Everyone is looking for solutions right now, because there is an urgent need for more doses,” Dr. Dean said. “But the dust has not settled on the best way to achieve this.”
2. Allergists offer reassurance regarding potential allergic reactions to C19 vaccines
- Reports of possible allergic reactions to the C19 vaccines produced by Pfizer-BioNTech and Moderna, both recently approved for emergency use by the U.S. Food and Drug Administration (FDA), have raised public concern. A team of experts led by allergists at Massachusetts General Hospital (MGH) has now examined all relevant information to offer reassurance that the vaccines can be administered safely even to people with food or medication allergies. The group’s review is published in the Journal of Allergy and Clinical Immunology: In Practice.
- In response to accounts of potential allergic reactions in some people following C19 vaccination in the United Kingdom, that country’s medical regulatory agency advised that individuals with a history of anaphylaxis to a medicine or food should avoid C19 vaccination.
- After closer review of the data related to allergic reactions, however, the FDA recommended that the vaccines be withheld only from individuals with a history of severe allergic reactions to any component of the C19 vaccine, and the Centers for Disease Control and Prevention advised that all patients be observed for 15 minutes post-vaccination by staff who can identify and manage such reactions. The U.S. agencies do not recommend that people with food or medication allergies avoid vaccination.
- To provide insights from allergists’ perspectives, Aleena Banerji, MD, clinical director of the Allergy and Clinical Immunology Unit at MGH and associate professor at Harvard Medical School, and her colleagues have summarized what’s currently known about allergic reactions to vaccines like those developed against C19, and they have proposed detailed advice so that individuals with different allergy histories can safely receive their first C19 vaccine. They also outline steps on safely receiving the second dose in individuals who develop a reaction to their first dose of C19 vaccine.
- “As allergists, we want to encourage vaccination by reassuring the public that both FDA-approved C19 vaccines are safe. Our guidelines are built upon the recommendations of U.S. regulatory agencies and provide clear steps to the medical community on how to safely administer both doses of the vaccine in individuals with allergic histories,” says Banerji.
- The experts note that allergic reactions to vaccines are rare, with a rate of about 1.3 per 1 million people. They also determined that the Pfizer-BioNTech and Moderna C19 vaccine allergic reactions will have a similarly low rate of occurrence. They stress that vaccine clinics will be monitoring all patients for 15 to 30 minutes and can manage any allergic reactions that occur. Banerji and her co-authors recommend that individuals with a history of anaphylaxis to an injectable drug or vaccine containing polyethylene glycol or polysorbate speak with their allergists before being vaccinated. They stress that patients with severe allergies to foods, oral drugs, latex, or venom can safely receive the C19 vaccines.
3. Britain takes a gamble with C19 vaccines, upping the stakes for the rest of us
- In an extraordinary time, British health authorities are taking extraordinary measures to beat back C19. But some experts say that, in doing so, they are also taking a serious gamble.
- In recent days, the British have said they will stretch out the interval between the administration of the two doses required for C19 vaccines already in use — potentially to as long as three months, instead of the recommended three or four weeks. And they have said they will permit the first dose and second dose for any one person to be from different vaccine manufacturers, if the matching vaccine is not available.
- The moves are borne of a desire to begin vaccinating as many people as quickly as possible, particularly with Britain facing high levels of transmission of an apparently more infectious form of the coronavirus (SARS-CoV-2).
- But they are also effectively turning that country into a living laboratory. The moves are based on small slices of evidence mined from “subsets of subsets” of participants in clinical trials, as one expert described it for STAT, and on general principles of vaccinology rather than on actual research into the specific vaccines being used. If the efforts succeed, the world will have learned a great deal. If they fail, the world will also have gained important information, though some fear it could come at a high cost.
- American health officials have dismissed the possibility that the U.S. would follow Britain’s lead, with Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, saying the vaccines in use — one made by Moderna, the other by the Pfizer and BioNTech partnership — will be deployed here using the schedules that were tested in Phase 3 trials that generated the evidence on which the Food and Drug Administration authorized the vaccines for emergency use.
- While data from both suggest the vaccines start to protect about 10 or 12 days after the first dose, it’s not known how long that initial protection lasts. In clinical trials, levels of neutralizing antibodies, which are thought to play a critical role in protecting against infection, were not substantial after the first dose of vaccine for the Pfizer vaccine.
- “While we think that single shot could give protection for more than four weeks, we just don’t know that. We don’t know when it’s going to drop off,” said John Mascola, director of NIAID’s Vaccine Research Center. Mascola said Operation Warp Speed, the federal government’s project to fast-track Covid vaccines, ruled out the possibility of altering vaccination schedules before Britain decided to do so.
- Paul Bieniasz of Rockefeller University is one of those who is watching the evolving situation in Britain with dread. A retrovirologist who turned from HIV research to work on SARS-2, Bieniasz is studying how the virus acquires mutations that allow it to evade the protective antibodies people develop when they have contracted Covid-19, or when they have been vaccinated against it.
- Bieniasz believes Britain is replicating in people the experiments he’s been doing in his lab — and could be fostering vaccine-resistant forms of the virus.
- On New Year’s Day he posted a short, sarcastic treatise — “Musings of an anonymous, pissed off virologist”— on Twitter outlining how one could go about rendering Covid vaccines “impotent,” if that was one’s goal. Giving millions of people who are at daily risk of contracting the disease incomplete protection by delaying the second dose of vaccine was key, he suggested.
- “My concern, as a virologist, is that if you wanted to make a vaccine-resistant strain, what you would do is to build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection,” Bieniasz told STAT. Even rolling out the vaccine at all when there is so much transmission occurring is far from ideal, he said, suggesting it would have been safer to beat down the amount of virus in circulation before beginning the vaccine deployment.
- “You are essentially maximizing the opportunity for the virus to learn about the human immune system. Learn about antibodies. Learn how to evade them,” he said.
- Isabella Eckerle, a coronavirus researcher at the Geneva Center for Emerging Viral Diseases, shares Bieniasz’s concern that Britain is increasing the potential for so-called escape mutants. She understands the public health imperative behind its approach, but worries about having large numbers of partially protected people for several months at a stretch. Britain is vaccinating its oldest citizens first. The immune systems of the elderly don’t function as well as those of younger adults; some will inevitably contract Covid while waiting for their second dose of vaccine, she said.
- Reports of partially vaccinated people contracting Covid may also erode confidence in the vaccines, Eckerle said: “If we fail to use this vaccine in a good way, it will damage the whole field of vaccinology for many, many years, I think.”
- Stephen Goldstein, a virologist at the University of Utah who specializes in coronaviruses, said that taking Britain’s approach at a time of limited supply of vaccine could create other problems.
- “If we vaccinate everybody with one dose and … six weeks later, the efficacy is now like 30% and we don’t have the doses to boost them at that point because we’ve used up their second doses on another round of first doses, it’s a disaster potentially,” he said.
- Not everyone agrees there is a disaster in the making. Some believe it makes sense, given Britain’s surge in cases and the rapid spread there of the B.1.1.7 variant, which studies suggest may be 50% more transmissible than the viruses it is quickly replacing.
- “At the core of my being, I really wish that we could adhere to the original schedule of vaccines, because that’s the safest thing to do,” said Akiko Iwasaki, a virologist and immunologist at Yale University who tweeted about her support for the British approach. “But seeing what’s happening in the world and just sort of looking at the situation of poor rollout and distribution, I’m feeling frustrated that we need to come up with some other options.”
- (Iwasaki was dismayed, though, to realize Britain’s instructions to clinicians that they could use a non-matching second dose of vaccine if that is their only option was not going to be done in the context of a clinical trial. While there is reason to believe boosting with a different type of vaccine might actually be useful in some cases — particularly if the first dose is a vaccine like the AstraZeneca vaccine that uses a harmless virus onto which genetic material from SARS-2 has been fused — the approach has not been studied at all in clinical trials.
- “They’re kind of wasting the opportunity if they’re just sort of randomly doing it and not even following up on the effectiveness of that combination,” Iwasaki said. “So yeah, I’m a lot more comfortable if it was a trial of some sort.”)
- Rajeev Venkayya, president of global vaccines for Takeda Pharmaceuticals, also believes Britain’s decision to stretch out the interval between vaccine doses is “justifiable.”
- “Of course we would all want to see vaccines used exactly as they were tested in Phase 3 efficacy trials. I don’t think there’s any debate about that. The question is: Do you have evidence to support flexibility? And here, I do think that — and this is specific to the AstraZeneca vaccine — it does appear that there is additional evidence that can support a modified recommendation,” said Venkayya, who served as special assistant to President George W. Bush and senior director for biodefense. In that role, Venkayya was the White House point person for pandemic preparedness efforts triggered by the spread of H5N1 bird flu.
- While the U.S.-based trial of the AstraZeneca vaccine is testing two doses given four weeks apart, studies the company conducted elsewhere gave some participants the two doses at intervals of six to eight weeks, or nine to 11 weeks, and some received the doses at an interval greater than 12 weeks.
- The Pfizer and Moderna vaccines are the first using mRNA technology, and the companies did not study those extended dosing schedules. Pfizer has objected to the proposal that the vaccine be used with a longer interval between vaccinations.
- Venkayya, whose thinking is influenced by his years in the White House, said sometimes policy has to be made without perfect data.
- “I think that to take the standards that we typically apply to the body of evidence we require before reaching decisions and recommendations on how to use vaccines, that by necessity has to change in the midst of a crisis like this,” he said. “I think there is the way we do medicine and public health in peacetime … where we have the luxury of taking the time we need and investing the resources and effort to collect enough data to reach a conclusion. You just don’t have that luxury in the midst of a crisis.”
4. The vaccine blame game
- In the week since our last newsletter, U.S. distribution of coronavirus vaccines has descended into turmoil. Now, millions of vaccines could expire before they reach people in need.
- The Trump administration predicted 20 million people would receive at least one dose of a C19 vaccine by the end of 2020. The final figure was about four million. And only 365,294 people in nursing homes and long-term-care centers have been vaccinated, despite more than 2.5 million doses distributed for those facilities, the Centers for Disease Control and Prevention reported.
- Critics say the U.S. government has mismanaged the rollout from top to bottom. Federal, state, and local officials blamed each other for botched logistics and funding shortfalls.
- State officials — struggling to handle outbreaks, mass testing campaigns, overflowing intensive care units and uncertain contact tracing — say they need more help from the federal government. And local governments are chafing at state restrictions.
- In New York City, only 110,000 people have received a vaccine dose — about a quarter of the total number received by the city. Mayor Bill de Blasio called on the state government — which has limited vaccinations to health care workers and those living and working at nursing homes — to allow older people and essential workers to receive the vaccine.
- Gov. Andrew Cuomo asserted that the problem was a local issue, and urging Mr. de Blasio and other local leaders to take “personal responsibility” for their performance. Mr. Cuomo also threatened to fine hospitals if they did not step up the vaccination rate.
- The $900 billion federal pandemic relief package will provide an additional $9 billion toward vaccination costs. But funds will arrive long after local health departments have started vaccinating residents. Slowdowns touch almost every part of the country.
- In Puerto Rico, a shipment of vaccines did not arrive until the workers who would have administered them had left for the Christmas holiday.
- In Houston, the city health department’s phone system crashed on the first day of a free vaccination clinic, after receiving more than 250,000 calls.
- In Tennessee, older people lined up on a sidewalk, leaning on walkers and wrapping themselves in blankets while they waited for a county health department to open its free clinic. The clinic exhausted its supply of vaccine before 10 a.m.
- In Florida, vaccine rollout sites continue to be overwhelmed in some places, with people waiting for hours. Gov. Ron DeSantis said hospitals may have future supplies of coronavirus vaccine reduced if they do not administer doses quickly enough.
- The U.S. is not alone: The Netherlands and France are just two of several countries that have been slow to roll out vaccinations. But the level of disorder in the U.S., as with the virus’s toll, seems unique.
- You can follow the U.S. rollout with the New York Times’ vaccine tracker.
Source: New York Times Coronavirus Briefing
F. Improved & Potential Treatments
1. Cheap hair lice drug may cut risk of C19 death by 80%
- A simple treatment for C19 could be cheaper than 20 bucks — and familiar to most grade school nurses.
- Head lice drug ivermectin is being explored as a potential treatment for the coronavirus following a promising new study that showed an 80% reduction in hospitalized C19 patient deaths.
- Just 8 out of 573 patients who received ivermectin passed away, compared to the 44 individuals out of 510 who died after being given a placebo.
- An earlier study of the antiparasitic prescription drug, which costs between $17 and $43 for a course of treatment, according to GoodRx, revealed promising results in April — by removing all viral RNA within 48 hours of a single dose.
- Liverpool University virologist Andrew Hill has called the new study “transformational” in the search for a coronavirus therapy. His findings, based on data from over 1,400 patients, were made public in a video posted to YouTube in which Hill discusses his results in a previously aired livestream. The research currently awaits peer review prior to publishing.
- “If we see these same trends observed consistently across more studies, then this really is going to be a transformational treatment,” said Hill.
- However, critics have called Hill’s study conclusion premature, urging further research before declaring ivermectin an effective treatment — citing other buzzed-about methods that ultimately failed to deliver, such as hydroxychloroquine and tocilizumab.
- “All we have are observational studies and clinicians’ opinions,” said University of Sydney professor Andrew McLachlan, the Daily Mail reported.
- “Many of the current studies have low numbers of participants, weak study designs, and inconsistent (and relatively low) ivermectin dosing regimes, with ivermectin frequently given in combination with other drugs.”
2. Drug used to treat cancer ‘could cure C19’
- A drug used to kill off cancer tumors for the last decade could cure C19, according to new research. In lab tests it outperformed remdesivir – the current standard anti-viral given to seriously ill patients.
- Pralatrexate, sold under the brand name Folotyn, was originally developed to kill lymphomas – tumours that originate in the glands.
- Study lead author Dr Haiping Zhang, of the Shenzhen Institutes of Advanced Technology in China, said: ‘Our study discovered it is able to potently inhibit coronavirus (SARS-CoV-2) replication. ‘It was stronger than remdesivir within the same experimental conditions.’
- The study, published in the journal PLOS Computational Biology, offers hope of reformulating it into a nasal spray. Remdesivir was the first major pharmacalogical breakthrough of the pandemic – speeding up recovery and boosting survival chances.
- Pralatrexate acts as a receptor – trapping the virus as it harmlessly degrades. Experiments on human cells found it worked by homing in on a viral protein known as RdRP.
- He explained: ‘Given current emergencies, repurposing approved drugs for C19 may provide a shortcut. They can be immediately tested in clinical trials. ‘These findings suggest pralatrexate could potentially be repurposed to treat C19.
- However, this chemotherapy drug can prompt significant side effects and is used for people with terminal lymphoma.’ It was approved by the US Food and Drug Administration in 2009 for patients with terminal disease – in spite of its toxicity. Dr Zhang said: ‘Therefore, we should be aware it does not guarantee the possibility of immediate use of the drug against C19.’
- The nose is a main entry point of the disease. Dissolving pralatrexate may offer hope of a nasal spray if side effects can be overcome. They include vomiting and fatigue.
- Pralatrexate, sold under the brand name Folotyn, belongs to a group of medicines called antifolates. It is used to treat patients aged 18 years or older with aggressive lymphoma after previous treatments have failed. It slows or stops the growth of cancer cells.
3. ‘Natural compounds’ could kill C19 spike protein
- A Tel Aviv-based start-up company claims it has proven in lab results that a combination of plant-based “natural compounds” can decompose the C19 spike protein that connects the virus to human cells.
- “The spike protein is the part in the virus that connects the virus to the cell,” explained Dr. Rachel R. Alkalay, a lawyer who holds a PhD from Queen Mary College in London but is not a medical doctor. “All the research in the world is focused on this spike protein. We managed to decompose it. Essentially, this is the equivalent of taking the fuel out of a car.”
- Alkalay told the Post that all of the compounds tested in the lab are “already approved and sold in the world for other purposes.” She add that, “Our findings show that it is very possible to have an immediate effect in inhibiting the virus in people who have been exposed.”
- Specifically, the research indicated that after six hours of treatment, the spike protein showed a 26% signal decrease relative to the non-treated incubated protein.
- Alkalay clarified that the pre-clinical experiments were meant to show early-bird proof that the virus proteins are decomposed by her company’s invention. She said that Novel Concepts Medical plans to carryout the necessary clinical trials and is looking for collaborators.
- The press release on the research did not name which specific natural compounds were included in the formula and Alkalay said she could not share specifics due to the pending patent.
- In a release, Alkalay said that, “We have encountered some resistance to the formula incorporating only natural compounds, but the lab results speak for themselves, and we are happy to be able to publish and share them in full. We are now looking for collaboration with hospitals to roll out clinical trials.”
4. 3 surprising drugs being repurposed to fight C19
- Here are three surprisingly ubiquitous drugs that are being tested as treatments for C19.
The BCG Vaccine
- Although you may not have heard of this vaccine, it’s one of the most widely used in the world, as well as one of the oldest. The Bacille Calmette-Guérin vaccine, named for the two French scientists who developed it, is one of the only vaccines being tested for C19 that was created to prevent a completely different disease: tuberculosis (TB).
- The vaccine has shown some promise in treating respiratory infections like C19, and studies examining the vaccine’s effect on C19 have had some encouraging results. A study published in November showed that in a group of about 6,000 healthcare workers, those who had received the BCG vaccine previously were less likely to have had C19 and generally had fewer symptoms.
- But an October analysis did not find a notable link between areas where the BCG vaccine is more frequently given and fewer deaths from C19, despite earlier analyses that did. The World Health Organization also says there’s not yet enough evidence to say if the vaccine is useful against C19.
- Importantly, no true clinical trials, which compare those who receive the vaccine to people who get a placebo, have been completed. But there are more than two dozen current clinical trials of the vaccine related to C19 worldwide, with one, a Mexican trial of 900 healthcare workers, due to be completed in January 2021.
- Although that trial and others might provide valuable data about how well the vaccine works against C19, the first U.S. BCG trials aren’t set to finish until November 2021. Although the U.S. and other counties have already approved C19-specific vaccines, the BCG vaccine, if proven effective against C19, could still provide protection to people unable to get one of the new vaccines. “It is a potentially important bridge that could offer some benefit until we have the most effective and safe C19 vaccines made widely available,” said Arditi. So a century-old TB vaccine could still become a valuable tool in fighting the C19 pandemic.
- To many, the name of the drug thalidomide conjures up horrifying images of the public health crisis it once caused. In the later ’50s and early ’60s, many pregnant women took thalidomide to treat morning sickness. But the drug, which hadn’t been tested in pregnant women, caused severe birth defects, like stunted or missing limbs. The crisis was so severe that it prompted the U.S. to impose many of the strict guidelines for drug testing that we have today.
- Thalidomide is still used, although not for morning sickness. In the U.S., it’s approved to treat multiple myeloma, a type of blood cancer, and complications of leprosy. It’s also been investigated as a treatment for many other conditions, like the H1N1 “swine flu” and idiopathic pulmonary fibrosis, a chronic lung disease that causes scar tissue to grow in the lungs. A small 2012 study of 23 patients with this condition found that thalidomide improved cough and other respiratory symptoms.
- Because thalidomide seems to decrease inflammation, can calm the immune system, and has had some success treating serious respiratory disease, some scientists think it could help decrease the inflammation that C19 causes and combat a “cytokine storm” — an immune system overreaction that severe C19 often induces.
- Given thalidomide’s history, however, researchers are understandably cautious about its repurposing. In a paper examining the evidence for thalidomide’s use against C19, researchers at the American University of Beirut in Lebanon and Hamad Bin Khalifa University in Qatar noted that thalidomide is approved to treat very few conditions because of its serious side effects. These include causing blood clots and long-term nerve damage. “Repurposing thalidomide based on the first glance at its proven efficiency in some pulmonary inflammatory conditions is inadequate,” write the authors.
- You might not think of melatonin as a drug at all; in the U.S, melatonin is considered a supplement and is not strictly regulated the way drugs are, although it’s a prescription drug in other counties. Melatonin is a hormone which helps regulate when we sleep and wake up, and many people take it to help them fall asleep. However, there’s conflicting data on whether it actually works as a sleep aid. In the U.S., melatonin is not approved to treat any medical condition, although it has been investigated, with mixed results, as a treatment for everything from cancer to high blood pressure.
- So it would be surprising if melatonin were approved to treat any medical condition, let alone C19. But many researchers think melatonin could benefit C19 patients. A team of Chinese and U.S. researchers published a paper in June asserting that melatonin might be useful as a C19 treatment because of effects it can have related to reducing inflammation, calming the immune system, and helping the body repair damage. Other researchers have echoed its promise, emphasizing that melatonin is very safe to use.
- Research so far has been promising, but preliminary. A recent analysis done by researchers at the Cleveland Clinic found that patients taking melatonin were nearly 30% less likely to be diagnosed with C19, and among African Americans, who have been particularly impacted by the pandemic, that number rose to 52%. Another study, which has not yet been reviewed by other scientists, found that both C19 and other patients who had to use ventilators fared better when given melatonin.
- “It is very important to note these findings do not suggest people should start to take melatonin without consulting their physician,” Feixiong Cheng, a computational biologist at the Cleveland Clinic’s Genomic Medicine Institute and the lead author on the first study, said in a press release. But he is “excited about the associations put forth in this study and the opportunity to further explore them.”
5. New Strategy Identifies Existing Drug That Inhibits Coronavirus – Outperforms Remdesivir
` Colorized scanning electron micrograph of an apoptotic cell (pink) heavily infected with the coronavirus (SARS-COV-2) particles (green), isolated from a patient sample.
- In lab experiments, pralatrexate outperforms remdesivir against the coronavirus (SARS-CoV-2).
- A novel computational drug screening strategy combined with lab experiments suggest that pralatrexate, a chemotherapy medication originally developed to treat lymphoma, could potentially be repurposed to treat C19. Haiping Zhang of the Shenzhen Institutes of Advanced Technology in Shenzhen, China, and colleagues present these findings in the open-access journal PLOS Computational Biology.
- With the C19 pandemic causing illness and death worldwide, better treatments are urgently needed. One shortcut could be to repurpose existing drugs that were originally developed to treat other conditions. Computational methods can help identify such drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes C19.
- To aid virtual screening of existing drugs, Zhang and colleagues combined multiple computational techniques that simulate drug-virus interactions from different, complimentary perspectives. They used this hybrid approach to screen 1,906 existing drugs for their potential ability to inhibit replication of SARS-CoV-2 by targeting a viral protein called RNA-dependent RNA polymerase (RdRP).
- The novel screening approach identified four promising drugs, which were then tested against SARS-CoV-2 in lab experiments. Two of the drugs, pralatrexate and azithromycin, successfully inhibited replication of the virus. Further lab experiments showed that pralatrexate more strongly inhibited viral replication than did remdesivir, a drug that is currently used to treat some C19 patients.
- These findings suggest that pralatrexate could potentially be repurposed to treat C19. However, this chemotherapy drug can prompt significant side effects and is used for people with terminal lymphoma, so immediate use for C19 patients is not guaranteed. Still, the findings support the use of the new screening strategy to identify drugs that could be repurposed.
- “We have demonstrated the value of our novel hybrid approach that combines deep-learning technologies with more traditional simulations of molecular dynamics,” Zhang says. He and his colleagues are now developing additional computational methods for generating novel molecular structures that could be developed into new drugs to treat C19.
G. Concerns & Unknowns
1. NIH Researchers Uncover Brain Damage in C19 Patients, Despite No Infection of the Brain
In an in-depth study, NIH researchers consistently found blood vessel damage in the brains of C19 patients but no signs of SARS-CoV-2 infections. Here is a high-resolution scan of a patient’s brain stem. Arrows point to light and dark spots that are indicative of blood vessel damage observed in the study.
- In an in-depth study of how C19 affects a patient’s brain, National Institutes of Health researchers consistently spotted hallmarks of damage caused by thinning and leaky brain blood vessels in tissue samples from patients who died shortly after contracting the disease. In addition, they saw no signs of the coronavirus (SARS-CoV-2) in the tissue samples, suggesting the damage was not caused by a direct viral attack on the brain. The results were published as a correspondence in the New England Journal of Medicine.
- “We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the body’s inflammatory response to the virus” said Avindra Nath, M.D., clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”
- Although C19 is primarily a respiratory disease, patients often experience neurological problems including headaches, delirium, cognitive dysfunction, dizziness, fatigue, and loss of the sense of smell. The disease may also cause patients to suffer strokes and other neuropathologies. Several studies have shown that the disease can cause inflammation and blood vessel damage. In one of these studies, the researchers found evidence of small amounts of SARS-CoV-2 in some patients’ brains. Nevertheless, scientists are still trying to understand how the disease affects the brain.
- “We were completely surprised. Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases,” said Dr. Nath.
- Finally, the researchers saw no signs of infection in the brain tissue samples even though they used several methods for detecting genetic material or proteins from SARS-CoV-2.
- “So far, our results suggest that the damage we saw may not have been not caused by the SARS-CoV-2 virus directly infecting the brain,” said Dr. Nath. “In the future, we plan to study how C19 harms the brain’s blood vessels and whether that produces some of the short- and long-term symptoms we see in patients.”
2. Loss of Smell and Taste May Affect Nutrition and Mental Health
- Until March, when everything started tasting like cardboard, Katherine Hansen had such a keen sense of smell that she could recreate almost any restaurant dish at home without the recipe, just by recalling the scents and flavors.
- Then the coronavirus arrived. One of Ms. Hansen’s first symptoms was a loss of smell, and then of taste. Ms. Hansen still cannot taste food, and says she can’t even tolerate chewing it. Now she lives mostly on soups and shakes.
- “I’m like someone who loses their eyesight as an adult,” said Ms. Hansen, a realtor who lives outside Seattle. “They know what something should look like. I know what it should taste like, but I can’t get there.”
- A diminished sense of smell, called anosmia, has emerged as one of the telltale symptoms of C19, the illness caused by the coronavirus. It is the first symptom for some patients, and sometimes the only one. Often accompanied by an inability to taste, anosmia occurs abruptly and dramatically in these patients, almost as if a switch had been flipped.
- Most regain their senses of smell and taste after they recover, usually within weeks. But in a minority of patients like Ms. Hansen, the loss persists, and doctors cannot say when or if the senses will return.
- Scientists know little about how the virus causes persistent anosmia or how to cure it. But cases are piling up as the coronavirus sweeps across the world, and some experts fear that the pandemic may leave huge numbers of people with a permanent loss of smell and taste. The prospect has set off an urgent scramble among researchers to learn more about why patients are losing these essential senses, and how to help them.
- “Many people have been doing olfactory research for decades and getting little attention,” said Dr. Dolores Malaspina, professor of psychiatry, neuroscience, genetics and genomics at Icahn School of Medicine at Mount Sinai in New York. “Covid is just turning that field upside down.”
- Smell is intimately tied to both taste and appetite, and anosmia often robs people of the pleasure of eating. But the sudden absence also may have a profound impact on mood and quality of life.
- Studies have linked anosmia to social isolation and anhedonia, an inability to feel pleasure, as well as a strange sense of detachment and isolation. Memories and emotions are intricately tied to smell, and the olfactory system plays an important though largely unrecognized role in emotional well-being, said Dr. Sandeep Robert Datta, an associate professor of neurobiology at Harvard Medical School.
- “You think of it as an aesthetic bonus sense,” Dr. Datta said. “But when someone is denied their sense of smell, it changes the way they perceive the environment and their place in the environment. People’s sense of well-being declines. It can be really jarring and disconcerting.”
- Many sufferers describe the loss as extremely upsetting, even debilitating, all the more so because it is invisible to others.
- “Smell is not something we pay a lot of attention to until it’s gone,” said Pamela Dalton, who studies smell’s link to cognition and emotion at the Monell Chemical Senses Center in Philadelphia. “Then people notice it, and it is pretty distressing. Nothing is quite the same.”
- British scientists studied the experiences of 9,000 C19 patients who joined a Facebook support group set up by the charity group AbScent between March 24 and September 30. Many members said they had not only lost pleasure in eating, but also in socializing. The loss had weakened their bonds with other people, affecting intimate relationships and leaving them feeling isolated, even detached from reality.
- “I feel alien from myself,” one participant wrote. “It’s also kind of a loneliness in the world. Like a part of me is missing, as I can no longer smell and experience the emotions of everyday basic living.”
- Another said, “I feel discombobulated — like I don’t exist. I can’t smell my house and feel at home. I can’t smell fresh air or grass when I go out. I can’t smell the rain.”
- Loss of smell is a risk factor for anxiety and depression, so the implications of widespread anosmia deeply trouble mental health experts. Dr. Malaspina and other researchers have found that olfactory dysfunction often precedes social deficits in schizophrenia, and social withdrawal even in healthy individuals.
- “From a public health perspective, this is really important,” Dr. Datta said. “If you think worldwide about the number of people with Covid, even if only 10% have a more prolonged smell loss, we’re talking about potentially millions of people.”
- The most immediate effects may be nutritional. People with anosmia may continue to perceive basic tastes — salty, sour, sweet, bitter and umami. But taste buds are relatively crude preceptors. Smell adds complexity to the perception of flavor via hundreds of odor receptors signaling the brain.
- Many people who can’t smell will lose their appetites, putting them at risk of nutritional deficits and unintended weight loss. Kara VanGuilder, who lives in Brookline, Mass., said she has lost 20 pounds since March, when her sense of smell vanished.
- “I call it the Covid diet,” said Ms. VanGuilder, 26, who works in medical administration. “There no point in indulging in brownies if I can’t really taste the brownie.”
- But while she jokes about it, she added, the loss has been distressing: “For a few months, every day almost, I would cry at the end of the day.”
- Smells also serve as a primal alarm system alerting humans to dangers in our environment, like fires or gas leaks. A diminished sense of smell in old age is one reason older individuals are more prone to accidents, like fires caused by leaving burning food on the stove.
- Michele Miller, of Bayside, N.Y., was infected with the coronavirus in March and hasn’t smelled anything since then. Recently, her husband and daughter rushed her out of their house, saying the kitchen was filling with gas.
- She had no idea. “It’s one thing not to smell and taste, but this is survival,” Ms. Miller said.
- Humans constantly scan their environments for smells that signal changes and potential harms, though the process is not always conscious, said Dr. Dalton, of the Monell Chemical Senses Center.
- Smell alerts the brain to the mundane, like dirty clothes, and the risky, like spoiled food. Without this form of detection, “people get anxious about things,” Dr. Dalton said.
- Even worse, some C19 survivors are tormented by phantom odors that are unpleasant and often noxious, like the smells of burning plastic, ammonia or feces, a distortion called parosmia.
- Eric Reynolds, a 51-year-old probation officer in Santa Maria, Calif., lost his sense of smell when he contracted C19 in April. Now, he said, he often perceives foul odors that he knows don’t exist. Diet drinks taste like dirt; soap and laundry detergent smell like stagnant water or ammonia.
- “I can’t do dishes, it makes me gag,” Mr. Reynolds said. He’s also haunted by phantom smells of corn chips and a scent he calls “old lady perfume smell.”
- It’s not unusual for patients like him to develop food aversions related to their distorted perceptions, said Dr. Evan R. Reiter, medical director of the smell and taste center at Virginia Commonwealth University, who has been tracking the recovery of some 2,000 C19 patients who lost their sense of smell.
- One of his patients is recovering, but “now that it’s coming back, she’s saying that everything or virtually everything that she eats will give her a gasoline taste or smell,” Dr. Reiter said.
- The derangement of smell may be part of the recovery process, as receptors in the nose struggle to reawaken, sending signals to the brain that misfire or are misread, Dr. Reiter said.
- After loss of smell, “different populations or subtypes of receptors may be impacted to different degrees, so the signals your brain is used to getting when you eat steak will be distorted and may trick your brain into thinking you’re eating dog poop or something else that’s not palatable.”
- Patients desperate for answers and treatment have tried therapies like smell training: sniffing essential oils or sachets with a variety of odors — such as lavender, eucalyptus, cinnamon and chocolate — several times a day in an effort to coax back the sense of smell. A recent study of 153 patients in Germany found the training could be moderately helpful in those who had lower olfactory functioning and in those with parosmia.
- Dr. Alfred Iloreta, an otolaryngologist at Mount Sinai Hospital in New York, has begun a clinical trial to see whether taking fish oil helps restore the sense of smell. The omega-3 fatty acids found in fish oil may protect nerve cells from further damage or help regenerate nerve growth, he suggested.
- “If you have no smell or taste, you have a hard time eating anything, and that’s a massive quality of life issue,” Dr. Iloreta said. “My patients, and the people I know who have lost their smell, are completely wrecked by it.”
- Mr. Reynolds feels the loss most acutely when he goes to the beach near his home to walk. He no longer smells the ocean or salt air.
- “My mind knows what it smells like,” he said. “And when I get there, it’s not there.”
H. The Road Back?
1. New MIT Model Could Help Determine Quarantine Measures Needed to Reduce C19’s Spread
- The number of people who become infected with C19 is directly related to how effectively a state maintains its quarantine measures, a new study finds.
- A key finding: Early reopening last spring led to a dramatic drop in “quarantine strength” in southern and west-central U.S. states.
- As C19 infections soar across the U.S., some states are tightening restrictions and reinstituting quarantine measures to slow the virus’ spread. A model developed by MIT researchers shows a direct link between the number of people who become infected and how effectively a state maintains its quarantine measures.
- The researchers described their model in a paper published in Cell Patterns in November, showing that the system could recapitulate the effects that quarantine measures had on viral spread in countries around the world. In their next study, recently posted to the preprint server medRxiv, they drilled into data from the United States last spring and summer. That earlier surge in infections, they found, was strongly related to a drop in “quarantine strength” — a measure the team defines as the ability to keep infected individuals from infecting others.
- The latest study focuses on last spring and early summer, when the southern and west-central United States saw a precipitous rise in infections as states in those regions reopened and relaxed quarantine measures. The researchers used their model to calculate the quarantine strength in these states, many of which were early to reopen following initial lockdowns in the spring.
The latest study focuses on early summer of this year, when the south and west-central United States saw a precipitous rise in infections. The researchers used their model to show quarantine strength dropped significantly in states that were early to reopen. Cr
- If these states had not reopened so early, or had reopened but strictly enforced measures such as mask-wearing and social distancing, the model calculates that more than 40% of infections could have been avoided in all states that the researchers considered. In particular, the study estimates, if Texas and Florida had maintained stricter quarantine measures, more than 100,000 infections could have been avoided in each of those states.
- “If you look at these numbers, simple actions on an individual level can lead to huge reductions in the number of infections and can massively influence the global statistics of this pandemic,” says lead author Raj Dandekar, a graduate student in MIT’s Department of Civil and Environmental Engineering.
- As the country battles a winter wave of new infections, and states are once again tightening restrictions, the team hopes the model can help policymakers determine the level of quarantine measures to put in place.
- “What I think we have learned quantitatively is, jumping around from hyper-quarantine to no quarantine and back to hyper-quarantine definitely doesn’t work,” says co-author Christopher Rackauckas, an applied mathematics instructor at MIT. “Instead, good consistent application of policy would have been a much more effective tool.”
- The team’s model is a modification of a standard SIR model, an epidemiological model that is used to predict the way a disease spreads, based on the number of people who are either “susceptible,” “infectious,” or “recovered.” Dandekar and his colleagues enhanced an SIR model with a neural network that they trained to process real C19 data.
- The machine-learning-enhanced model learns to identify patterns in data of infected and recovered cases, and from these data, it calculates the number of infected individuals who are not transmitting the virus to others (presumably because the infected individuals are following some sort of quarantining measures). This value is what the researchers label as “quarantine strength,” which reflects how effective a region is in quarantining an infected individual. The model can process data over time to see how a region’s quarantine strength evolves.
In simulated scenarios, the team shows that if states southern and west-central states had opened later, and maintained quarantine strength, more than 40% of Covid-19 infections could have been avoided.
- The researchers developed the model in early February and have since applied it to C19 data from more than 70 countries, finding that it has accurately simulated the on-the-ground quarantine situation in European, South American, and Asian countries that were initially hard-hit by the virus.
- “When we look at these countries to see when quarantines were instituted, and we compare that with results for the trained quarantine strength signal, we see a very strong correlation,” Rackauckas says. “The quarantine strength in our model changes a day or two after policies are instituted, among all countries. Those results validated the model.”
- The team published these country-level results last month in Cell Patterns, and are also hosting the results at covid19ml.org, where users can click on a map of the world to see how a given country’s quarantine strength has changed over time.
What if states had delayed?
- Once the researchers validated the model at the country level, they applied it to individual states in the U.S., to see not only how a state’s quarantine measures evolved over time, but how the number of infections would have changed if a state modified its quarantine strength, for instance by delaying reopening.
- They focused on the south and west-central U.S., where many states were early to reopen and subsequently experienced rapid surges in infections. The team used the model to calculate the quarantine strength for Arizona, Florida, Louisiana, Nevada, Oklahoma, South Carolina, Tennessee, Texas, and Utah, all of which opened before May 15. They also modeled New York, New Jersey, and Illinois — states that delayed reopening to late May and early June.
- They fed the model the number of infected and recovered individuals that was reported for each state, starting from when the 500th infection was reported in each state, up until mid-July. They also noted the day on which each state’s stay-at-home order was lifted, effectively signaling the state’s reopening.
- For every state, the quarantine strength declined soon after reopening; the steepness of this decline, and the subsequent rise in infections, was strongly related to a state’s reopening. States that reopened early on, such as South Carolina and Tennessee, had a steeper drop in quarantine strength and a higher rate of daily cases.
- “Instead of just saying that reopening early is bad, we are actually quantifying here how bad it was,” Dandekar says.
- Meanwhile, states like New York and New Jersey, which delayed reopening or enforced quarantine measures such as mask-wearing even after reopening, kept a more or less steady quarantine strength, with no significant rise in infections.
- “Now that we can give a measure of quarantine strength that matches reality, we can say, ‘What if we kept everything constant? How much difference would the southern states have had in their outlook?’” Rackauckas says.
- Next, the team reversed its model to estimate the number of infections that would have occurred if a given state maintained a steady quarantine strength even after reopening. In this scenario, more than 40% of infections could have been avoided in each state they modeled. In Texas and Florida, that percentage amounts to about 100,000 preventable cases for each state.
- Conceivably, as the pandemic continues to ebb and surge, policymakers could use the model to calculate the quarantine strength needed to keep a state’s current infections below a certain number. They could then look through the data to a point in time where the state exhibited this same value, and refer to the type of restrictions that were in place at that time, as a guide to the policies they could put in place at the present time.
- “What is the rate of growth of the disease that we’re comfortable with, and what would be the quarantine policies that would get us there?” Rackauckas says. “Is it everyone holing up in their houses, or is it everyone allowed to go to restaurants, but once a week? That’s what the model can kind of tell us. It can give us more of a refined quantitative view of that question.”
2. How Does New York Keep Transit Riders Safe From C19? Trial & Error.
- The nation’s largest transit operator, New York’s Metropolitan Transportation Authority, is trying to figure out how to move people safely during the coronavirus pandemic. So far, it hasn’t been easy.
- The MTA is spending hundreds of millions of dollars this year scrubbing stations, commuter trains, subways and buses. It also is investing millions of dollars to test new technologies in a trial-and-error approach.
- The MTA, which has an annual budget of $17 billion, spent $1.3 million on a pilot program to sanitize subway cars and buses using ultraviolet light. But the authority gave up on the technology because the process of emptying the vehicles, setting up the equipment and using it isn’t practical on a fleet numbering in the thousands, Mr. Dowd said.
- The authority spent $775,000 on antimicrobial sprays that were supposed to kill viruses and bacteria for days or weeks after they were applied to surfaces. Mr. Dowd said most of the sprays proved ineffective.
- Officials of the state of Connecticut, which relies on the MTA to carry 95% of its rail commuters on several Metro-North lines, say they have a high degree of confidence in the railroad.
- Connecticut transportation officials have taken a more basic approach to fighting the virus on its bus and rail services, which are operated by third parties.
- Rich Andreski, Connecticut’s bureau chief for public transportation, said he and his colleagues commissioned a report from Yale University earlier this year to assess best practices for making rail travel safe during the pandemic.
- Mr. Andreski said the report was needed, in part, because of the way scientific opinion shifted this year from the importance of cleaning surfaces toward the need to filter out virus particles in the air.
- The Yale researchers rejected technologies such as ultraviolet light as impractical for cleaning surfaces in vehicles. Instead, they recommended the state focus on basics, such as ensuring riders wear masks and social distance to the greatest extent possible while the agency improves ventilation.
- The researchers told Connecticut officials that its railcar ventilation systems already exchange air with outdoor air every six minutes, limiting the risk to riders. “That was an eye opener for us,” Mr. Andreski said.
- Krystal Pollitt, an assistant professor of epidemiology at Yale School of Public Health, recommended the state upgrade the filters on heating, ventilating and air conditioning systems, from a class of filter that removes 50% of aerosols to a filter that removes 80% of aerosols, which would further reduce risk to riders.
- Transit agencies currently are able to maintain social distancing on most trains and buses because ridership is low. Weekday commuter rail ridership in the New York metropolitan region is down more than 70%. Ridership is likely to remain low for some time because many white-collar workers continue to work remotely and many nonessential businesses remain closed.
- Studies and reports this year have drawn conflicting conclusions about the extent to which the coronavirus spreads on mass transit.
- The MTA says trains and buses haven’t been linked to C19 clusters in the U.S. or overseas. But the authority did recently team up with the U.S. Department of Homeland Security and Massachusetts Institute of Technology to study how the virus might spread through a subway car or bus.
- Mr. Dowd said basics such as mask-wearing and ventilation are important. But he said it is also up to transit agencies to test new products that might help reduce risk for passengers.
- In November, Metro-North released a feature in the railroad’s customer phone app that tells riders how much available space there is in each car of an approaching train.
- ”We are not going to have people in the trains unless we can convince them it’s safe,” said Catherine Rinaldi, Metro-North’s president. ”And we need to be innovating constantly to be able to identify the technology to keep them safe.”
I. Back to School!?
1. Children are wearing masks up to 4.5 hours per day. What effect is this having on their health?
- Researchers at the University of Witten in Germany created an online survey and registry where parents, doctors, pediatricians and others could document their observations regarding the effect of children wearing masks. The results, summarized below, report the results from the parents, who entered data on a total of 25,930 children.
- The average wearing time of the mask was 270 minutes per day. Impairments caused by wearing the mask were reported by 68% of the parents. These included irritability (60%), headache (53%), difficulty concentrating (50%), less happiness (49%), reluctance to go to school (44%), malaise (42%) impaired learning (38%) and drowsiness or fatigue (37%).
- According to the researchers, the frequency of the registry’s use and the spectrum of symptoms registry indicate the importance of the topic and call for representative surveys, randomized controlled trials with various masks and a renewed risk benefit assessment for the vulnerable group of children.
2. Children much more likely to asymptomatic than adults
- A key factor in the spread of C19 in schools is symptomless cases. Most scientists believe that between 30% and 40% of adults do not display any Covid symptoms on the day of testing, even if they have been infected. For children, however, this figure is higher.
- “It is probably more like 50% for those in secondary school while for boys and girls in primary school, around 70% may not be displaying symptoms even though they have picked up the virus,” says Professor Martin Hibberd of the London School of Hygiene and Tropical Medicine.
- That is a large proportion of symptom-free disease-carriers within a population. What is not yet known is just how much infection is being passed on by this cohort of young symptom-free carriers. It is a critically important issue, and one that will play a key role in determining the effect of C19 on the people of Britain in the next few weeks, say researchers.
- Unfortunately a definitive answer on the infectiousness of young people remains tantalisingly out of reach, although there is evidence to suggest that people who don’t display symptoms of C19 may have lower viral loads, which means they are less likely to infect others.
- This tendency correlates with age, so younger children have lower viral loads. As a result, they are less likely to display symptoms – and also less likely to pass on the virus. “It’s a real possibility but we cannot yet be sure,” says Hibberd.
- One solution to the problem is to increase testing in schools. This would require the widespread deployment of rapid testing, particularly with the lateral flow method, which is easily administered and gives results in less than half an hour. It is less accurate than the standard PCR swab test, however, and there have been concerns about a high level of false negative results leading to the continued spread of the new, more infectious, variant of the coronavirus.
- However, scientists point out that rapid tests are better at spotting individuals with high viral loads than those with lower ones.
- “We know that a high viral load is a key issue affecting the virus’s transmission, so even if we can’t detect every carrier, we are most likely to pick up those children who are more likely to transmit,” says Hibberd.
J. Projections & Our (Possible) Future
1. From vaccines to safe socialization: Here’s what to expect in 2021
- So what will life look like in 2021? Here’s when you might be able to do various activities in a post-pandemic world, based on what we know now:
Everyone gets vaccinated
- When to expect it: Second quarter of 2021
- Fauci and other experts predict that by the second quarter of 2021, the “overwhelming majority of the population” will be able to get vaccinated, he told CNBC’s “Healthy Returns” conference Dec. 16. In March and early April, for example, people without underlying health conditions could walk into a drugstore and get the vaccine.
- Testing vaccines for young children will likely begin around the second quarter, and kids could be vaccinated by the end of 2021, Dr. Jose Romero, the chair of the CDC’s Advisory Committee for Immunization Practices, said during an interview on MSNBC Dec. 4.
- But it will still take more data and time to determine whether the current vaccines can effectively prevent transmission, Brittany Kmush, assistant professor of public health at Syracuse University who specializes in infectious disease epidemiology, tells CNBC Make It. “We know they’re very effective at preventing disease, and definitely death, but what we don’t know is how good they are at preventing infection,” she says.
- Given that, “hopefully by the second part of 2021, we can start seeing a significant decline [in infections], and hopefully a control of this disease,” Antonio Crespo infectious diseases physician and medical director at Orlando Health, tells CNBC Make It.
Having a large outdoor gathering without masks
- When to expect it: Summer of 2021
- “I expect in July, to be able to have a barbecue outside of my house and have 15-20 people over not be freaking out,” Jha said. “Try to get people to make a little distance, maybe a little. Masks, we can talk about that. If they come inside the house, definitely mask but maybe outside.”
- In communities where vaccine acceptance is high above 80%, “that’ll make a massive difference,” he said.
Returning to the office
- When to expect it: Second half of 2021
- If workplaces decide that employees will return to physical offices versus work from home permanently, the timing of that transition should depend upon the amount of virus spread and the level of protection (vaccination) in a community.
- Surveillance testing, in which a certain percentage of a specific population is monitored to track increasing or decreasing prevalence, could be crucial for employers to assess the risks and make decisions about returning to the workplace.
- When to expect it: It will be gradual.
- “When you move from one location to another, different places may have different rates of Covid-19,” as well as different percentages of people who are vaccinated, Crespo says.
- According to Fauci, travel will gradually ease up as people begin to get vaccinated, he told the New York Times Dec. 16. “There is no black and white, light switch on, light switch off,” he said.
Safely eating indoors at restaurants
- When to expect it: Fall of 2021
- Safe indoor dining could resume as early as the fall of 2021, when a significant amount of the population has been vaccinated, Fauci told CNBC’s “Healthy Returns” Dec. 16. “But again, it’s going to depend on what proportion of the population gets vaccinated,” he said. And it still may involve some social distancing until there is “a profound degree of herd immunity,” Fauci said.
- Bars, which Fauci has singled out as hotspots that can spread infections, will likely take even longer to resume normal operations without masks or restrictions.
Going to theaters without a mask
- When to expect it: Middle or end of 2021
- “I don’t believe we’re going to be able to throw the masks away and forget about physical separation in congregate settings for a while, probably likely until we get into the late fall and early next winter,” Fauci said during a Center for Strategic and International Studies virtual health event Dec. 15. “But I think we can do it.”
Hosting big weddings
- When to expect: Spring or summer 2022
- People hoping to get married in 2021 should wait until the second half of the year, and make appropriate adjustments to the gathering, Crespo says. “As always, doing it outdoors would be preferable, maybe limiting the amount of people,” he says. “If you’re going to have a reception, you may have to separate the seats and encourage mask wearing.”
K. Practical Tips & Other Useful Information
1. Some Masks Can Be Worse Than Not Wearing One at All
Pressure and particle motions with and without a mask.
- Even though it has been widely known that wearing a face mask will help mitigate the community spread of C19, less is known regarding the specific effectiveness of masks in reducing the viral load in the respiratory tracts of those wearing them.
- In Physics of Fluids, by AIP Publishing, researchers from the University of Massachusetts Lowell and California Baptist University examined the effect of wearing a three-layer surgical mask on inspiratory airflows and the mask’s effects on the inhalation and deposition of ambient particles in the upper respiratory airways.
- “It is natural to think that wearing a mask, no matter new or old, should always be better than nothing. Our results show that this belief is only true for particles larger than 5 micrometers, but not for fine particles smaller than 2.5 micrometers,” said author Jinxiang Xi. (The SARS-CoV-2 virus that causes C19 is about 0.1 micrometers. — ed.)
- The researchers found that wearing a mask with low (less than 30%) filtration efficiency can be worse than without.
- They developed a computational face mask model using a physiologically realistic model of a person wearing a surgical mask with pleats and then using numerical methods to track the particles through the mask. They examined the behavior and fates of aerosols passing through the mask, onto the face, into the airway, and, eventually, where they deposit in the nose, pharynx, or deep lung.
- The model showed a mask changes the airflow around the face, so that instead of air entering the mouth and nose through specific paths, air enters the mouth and nose through the entire mask surface but at lower speeds.
- The lower speed near the face favors the inhalation of aerosols into the nose, so even though masks filter out certain numbers of particles, more particles escaping mask filtration can enter the respiratory tract.
- They found the filtration efficiency of the three-layer surgical mask can vary from 65%, if new, to 25%, when used, so wearing a 65% mask properly will provide good protection, but wearing a 25% filtration mask can be worse than not wearing one at all.
- “We hope public health authorities strengthen the current preventative measures to curb C19 transmission, like choosing a more effective mask, wearing it properly for the highest protection, and avoid using an excessively used or expired surgical mask,” said Xi.
- The researchers found the pleats of a surgical face mask significantly affect airflow patterns, suggesting that mask shape should also be considered as an important factor when estimating mask protection efficiency and designing new masks. Xi said they will further study the effects of mask shapes on human airway protection efficiency.
2. Six Ways to ‘Reboot Your Brain’ After a Hard Year of C19
- There’s no doubt that 2020 was difficult for everyone and tragic for many. But now vaccines against C19 are finally being administered – giving a much needed hope of a return to normality and a happy 2021.
- However, months of anxiety, grief and loneliness can easily create a spiral of negativity that is hard to break out of. That’s because chronic stress changes the brain. And sometimes when we’re low we have no interest in doing the things that could actually make us feel better.
- To enjoy our lives in 2021, we need to snap out of destructive habits and get our energy levels back. In some cases, that may initially mean forcing yourself to do the things that will gradually make you feel better. If you are experiencing more severe symptoms, however, you may want to speak to a professional about therapy or medication.
- Here are six evidenced-based ways to change our brains for the better.
#1 Be kind and helpful
- Kindness, altruism and empathy can affect the brain. One study showed that making a charitable donation activated the brain’s reward system in a similar way to actually receiving money. This also applies to helping others who have been wronged.
- Volunteering can also give a sense of meaning in life, promoting happiness, health and wellbeing. Older adults who volunteer regularly also exhibit greater life satisfaction and reduced depression and anxiety. In short, making others happy is a great way to make yourself happy.
- Exercise has been linked with both better physical and mental health, including improved cardiovascular health and reduced depression. In childhood, exercise is associated with better school performance, while it promotes better cognition and job performance in young adults. In older adults, exercise maintains cognitive performance and provides resilience against neurodegenerative disorders, such as dementia.
- What’s more, studies have shown that individuals with higher levels of fitness have increased brain volume, which is associated with better cognitive performance in older adults. People who exercise also live longer. One of the very best things that you can do to reboot your brain is in fact to go out and get some fresh air during a brisk walk, run or cycling session. Do make sure to pick something you actually enjoy to ensure you keep doing it though.
#3 Eat well
- Nutrition can substantially influence the development and health of brain structure and function. It provides the proper building blocks for the brain to create and maintain connections, which is critical for improved cognition and academic performance. Previous evidence has shown that long-term lack of nutrients can lead to structural and functional damage to the brain, while a good quality diet is related to larger brain volume.
- One study of 20,000 participants from the UK-Biobank showed that a higher intake of cereal was associated with the long-term beneficial effects of increased volume of grey matter (a key component of the central nervous system), which is linked to improved cognition. However, diets rich in sugar, saturated fats or calories can damage neural function. They can also reduce the brain’s ability to make new neural connections, which negatively affects cognition.
- Therefore, whatever your age, remember to eat a well-balanced diet, including fruits, vegetables and cereal.
#4 Keep socially connected
- Loneliness and social isolation is prevalent across all ages, genders and cultures – further elevated by the C19 pandemic. Robust scientific evidence has indicated that social isolation is detrimental to physical, cognitive and mental health.
- One recent study showed that there were negative effects of C19 isolation on emotional cognition, but that this effect was smaller in those that stayed connected with others during lockdown. Developing social connections and alleviating loneliness is also associated with decreased risk of mortality as well as a range of illnesses.
- Therefore, loneliness and social isolation are increasingly recognised as critical public health issues, which require effective interventions. And social interaction is associated with positive feelings and increased activation in the brain’s reward system.
- In 2021, be sure to keep up with family and friends, but also expand your horizons and make some new connections.
#5 Learn something new
- The brain changes during critical periods of development, but is also a lifelong process. Novel experiences, such as learning new skills, can modify both brain function and the underlying brain structure. For example juggling has been shown to increase white matter (tissue composed of nerve fibers) structures in the brain associated with visuo-motor performance.
- Similarly, musicians have been shown to have increased grey matter in the parts of the brain that process auditory information. Learning a new language can also change the structure of the human brain.
- A large review of the literature suggested that mentally stimulating leisure activities increase brain-reserve, which can instil resilience and be protective of cognitive decline in older adults – be it chess or cognitive games.
#6 Sleep properly
- Sleep is an essential component of human life, yet many people do not understand the relationship between good brain health and the process of sleeping. During sleep, the brain reorganises and recharges itself and removes toxic waste byproducts, which helps to maintain normal brain functioning.
- Sleep is very important for transforming experiences into our long-term memory, maintaining cognitive and emotional function and reducing mental fatigue. Studies of sleep deprivation have demonstrated deficits in memory and attention as well as changes in the reward system, which often disrupts emotional functioning. Sleep also exerts a strong regulatory influence on the immune system. If you have the optimal quantity and quality of sleep, you will find that you have more energy, better well being and are able to develop your creativity and thinking.