December 18, 2020
FDA Advisory Panel Confirms Moderna’s C19 Vaccine Benefits Outweigh Risks – clearing the way for up to 6,000,000 doses being distributed as early as next week
US coronavirus cases and deaths break records
“I know the virus is real. But, until I see that vaccines are actually safe for myself or my kids to take, I’m not going to take it.”Jonathan Damato, NYC paramedic for 21 years
“You don’t have to cancel Christmas this year — just keep gatherings small.”Dr. Fauci, denying he ever said that Christmas should be cancelled as widely reported on social media
“Mayors and governors have been ordering soul-crushing shutdowns yet again. It’s excruciatingly obvious at this point that the virus is going to do what it’s going to do. The mitigation measures have catastrophic side effects and — even if intuitively they may seem to make sense — don’t really accomplish anything with this virus.”Thomas E. Woods Jr., author and podcaster
“New York has 25% more COVID hospitalizations per capita than Florida, and is worse in every other cumulative and current metric. Florida is completely open, while New York is irrationally closed. Nobody I talk to in NYC knows that data. Nobody.”Eli Klein, who runs an art gallery in New York City, questioning the effectiveness of lockdowns and New Yorkers’ blind acceptance of them
What We Saw On Our Wedding Trip:
- Wedding took place in Memphis, TN on 12/12 (postponed from May)
- Father of bride tested positive and missed the wedding (watched via live stream)
- Mother walked the bride down the aisle and did “father/daughter” dance
- Approx. 40 guests (out of 200+ invited), most attending live in or near Memphis
- Plenty of space for wedding and reception, but little social distancing (especially on dance floor)
- Almost no one wore a mask (except for staff)
- Many restaurants in Memphis and Nashville are open, but close early (or is that normal there?)
- Little traffic at the malls, hotels, restaurants and tourist attractions we went to
- Not many people on flights or at airports (except for moderate crowds at Atlanta airport)
- Fewer homes seemed to be decorated for Christmas than usual
- Blue Christmas seemed to be playing a lot on the car radio
- Dr. Fauci would not approve
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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, Patients in ICU & Positivity
- U.S. Sets Records for Newly Reported Infections, Deaths
- Safe Social Distancing Alert: Long Streams of Virus-Laden Droplets Can Trail Behind Infected Individuals (!) (*)
- Women at less risk of severe disease or death from C19
- Patients on ACE inhibitors, ARBs, don’t have higher C19 risk (*)
- Gene Identified That Could Explain Why C19 Causes No Symptoms in Some and Serious Illness or Death in Others
- Four genetic variants are linked to severe C19
- Researchers Uncover Evidence That UV Radiation From Sunlight Reduces C19 Transmission
- Ferrets, Cats, Civets, and Dogs Most Susceptible to Coronavirus Infection After Humans (!) (*)
- A C19 Vaccine Playbook: What to Expect and When (Taking Effect, Duration, Returning to Normal Life) (!) (*)
- What are the ingredients of Pfizer’s C19 vaccine?
- A guide to who can safely get the Pfizer C19 vaccine (*)
- Phase III Clinical Trial Success: Oxford C19 Vaccine Is Safe and Protects Against Disease
- FDA approves first over-the-counter C19 test that delivers near-instant results (!)
- New Research Shows Remdesivir Is Likely a Highly Effective Antiviral Against C19 (!) ©
- NIH Clinical Trial: Baricitinib Plus Remdesivir Shows Promise for Treating C19
- Scientists are studying discovery of a new C19 variant (!)
- Research strongly suggests C19 virus enters the brain
- C19 Attacks Testicles, May Affect Male Fertility
- Obese C19 patients have poor outcomes not driven by inflammation
- Coronavirus-like particles very sensitive to temperature ©
- Antibodies as C19 insurance
- At Least 25% of World May Not Have Access to a C19 Vaccine Until 2022 (*)
- Detecting C19 in Less Than 5 Minutes With a Paper-Based Electrochemical Sensor (!)
- Your Old Radiator Is a Pandemic-Fighting Weapon (!) (*)
- Your home is a hotspot for C19 (*)
- Which C19 Rules Are Useless? Too Many of Them (*)
- COVID Face Shields No Match for Sneeze Vortex Rings (*)
M. Linked Stories
- How C19 Is Negatively Impacting Those Who Are Not Infected
- Who’s to Blame? How the Media Has Shaped Public Understanding of the C19 Pandemic
- New C19 Test Targets Three Viral Genes to Increase Reliability – Could Reduce Virus Spread
- A Shock to the PPE System: New Method for Recharging N95 Masks to Meet COVID Demand
- Battling C19: Researchers Discover Materials – Activated With UV Light – That Can Kill Coronavirus and Other Viruses
- Alcohol-Free Hand Sanitizer Just As Effective Against C19 Virus As Alcohol-Based Versions (*)
- Where to Sit in a Car and Which Windows to Put Down to Prevent C19 Transmission (*)
- Portable Saliva-Based Smartphone Platform Could Rapidly Expand C19 Testing
- Researchers Discover How the C19 Virus Hijacks and Rapidly Damages Human Lung Cells
- Why RNA Vaccines for C19 Raced to the Front of the Pack
- New Insights Into Why C19 Infects Some Animals, but Not Others
- Engineers Designing More Responsive Coronavirus Wastewater Testing to Monitor C19 Spread
- New U.S. Research Confirms C19 Complications: Lung, Kidney and Cardiovascular Issues
- Computational Model of a Human Lung Cell Predicts Drug Targets Against C19
- Coronavirus spread during dental procedures could be reduced with slower drill rotation
- Healthcare workers have increased insomnia, risk of severe mental health problems
- UCI researchers create model to calculate C19 health outcomes
- C19 has an odor, and the dogs are detecting it
- Has a year of living with C19 rewired our brains?
- A portrait of the coronavirus: how it spreads, infects, and sickens
- 2 months without alcohol? Russian C19 vaccine warning draws backlash
A. Pandemic Headlines
(In no particular order)
- You can access all of the updates on our website at https://dailycovid19post.com/. Please share the website address with anyone you believe might be interested in the updates.
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- We do not endorse, and may not agree with, any opinion or view included in this update. We include a wide spectrum of opinions and views as we believe that it gives perspective on what people are thinking and may give insights into our future.
- Pfizer vaccine vials hold extra doses, could expand US supply
- “Who Wants To Be A Guinea Pig?”: Health Workers Balk At Vaccine; 40% Of Staff At One Chicago Hospital Refuse To Take
- Pfizer “Closely Monitoring” Alaska Health Worker After “Serious Adverse Reaction” To Vaccine
- Australian Study Finds “High Level” of Resistance to COVID Vaccine
- Joe Biden to publicly receive COVID-19 vaccine next week: report
- Early vaccinations for members of Congress and Supreme Court justices
- Oliver Stone says he took Russia’s COVID-19 vaccine
- Texas Governor: It’s Time to Put Lockdowns Behind Us
- VP Elect Harris: People who do not wear masks will not be punished
- “The State Has Provided No Evidence”: San Diego Judge Nukes CA Gov. Newsom’s Lockdown For Strip Clubs And Restaurants
- Mexico’s President Slams Lockdowns As A Form Of “Dictatorship”
- NYC Mayor Floats Post-Christmas Full Lockdown, But Final Decision Rests With Gov. Cuomo
- NBC Medical Expert: People shouldn’t travel or be free of wearing masks until next summer, even if they have been vaccinated
- WHAT THE SHOT! Only 4,000 COVID vaccinations given in New York so far (of 80,000 received)
- After weeks of Holier Than Thou Howling, The Thanksgiving Surge is a No Show
- Data Shows Fears Of Overwhelmed Medical System Overblown, Ample Hospital Capacity Nationwide –Covid patients occupy only 15% of hospital beds
- Counting the dead by the hour as I.C.U.s fill up
- A million new cases in five days as U.S. outbreak picks up speed
- NYC hospitals nix elective surgeries as COVID-19 rate hits 6%
- US 7-day average cases breaks string of records
- UK has vaccinated nearly 140,000 people but warns rollout may take longer than anticipated
- At least 2 states now publishing vaccination data
- FDA approves first at home test
- Midwestern cases been falling for a month
- Hospitalizations in northeast surge
- Western US now worst-hit region
- Stockholm may suspend all non-emergency care as COVID crushes capacity
- Denmark may expand local lockdowns
- Europe faces pressure to speed up vaccine approval
- Boston tightens COVID restrictions
- Italy mulls holiday lockdown
- NJ sees surge in patients on ventilators; most new cases since May
- Netherlands PM says lockdown will last at least 5 weeks
- Netherlands follows Germany into hard lockdown
- US average deaths exceed 2,500 per day
- South Korea reports record COVID deaths as lockdown fears spark panic buying
- Italian government warns of new restrictions to come
- Singapore approves Pfizer vaccine
- Malaysia president pledges free vaccinations for all
- Did COVID Murder The Flu?
- The Number Of Americans That Are Depressed Or Suicidal Has Soared Because Of The COVID Lockdowns
- NY’s nursing homes STILL ‘acutely vulnerable’ to COVID-19: report
- Married teachers die of COVID-19 while holding hands
- NYC’s Mass Transit Authority to keep cleaning 24/7 despite few cases of COVID-19 surface spread
- Utah Mink First Wild Animal In US To Test Positive For Mutated Coronavirus
- When 2-Year-Olds Are Thrown Off Airplanes, You Know America Has Changed
- Initial Jobless Claims Surge To Highest In Almost 4 Months
- A Record 61% Of Restaurants, 35% Of Small Businesses Can’t Pay December Rent
- Low Income Households Are Blowing Through Savings Much Faster Than High Earners
- 17 million Americans are estimated to be not current on their mortgage or rent, with more than 5 million possibly facing eviction within 2 months
- Evictions return, and some sheriffs try for a humane approach
- No shirt, no shoes, no shot, no service – hotels consider requiring all guests to have COVID vaccination
- Coke Firing 12% Of US Workers Due To Covid
- Manhattan Apartment Prices Just Crashed To 10 Year Lows
- New York’s Iconic 21 Club To Close “Indefinitely” Due To COVID
- Death row inmate set to be executed next month tests positive for COVID-19
- Maine residents will be issued a card along with COVID-19 shot
- New York company to start human trials of nasal drop COVID-19 vaccine
- COVID-19 vaccine may be mandatory for NYPD cops after all
- Florida governor to keep restaurants open amid pandemic
- Cops respond after text autocorrects ‘swabbed’ to ‘stabbed’
- ‘I cry in the car’: Pandemic takes emotional toll on ICU nurse manager
- US student jailed for violating quarantine in Cayman Islands: reports
- Japan’s ‘Pajama Suit’ helps you look good for Zoom calls
- Pandemic boosts business for Christmas tree farms across US
- Paul McCartney loves wearing a face mask: ‘I can go anywhere and do anything’
- Survey finds cheaters want COVID-19 vaccine so they can have ‘responsible’ affairs
- Lockdown love story: Man jet skied across Irish Sea to girlfriend – he was put in jail
- “How To Make A Face Mask?” – 2020’s Top UK Google Searches
- Masks may soon come with labels saying how well they work
New Yorkers eating outside in a snow storm because inside dining has been locked down.
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 75,261,131 (approx. 1% of world population)
- New Cases (7 day average) = 642,087
- Second highest number of new cases, the highest was on 12/16
- Record high 7 day average of new cases
- 7 day average of new cases are increasing at a rapid rate
- During the last 30 days, the 7 day average has increased from 564,334 to 642,087, an increase of 13.8%, which translates into an annualized increase of 165.6% (!)
US Cases & Positivity Rates:
- Total Cases = 17,627,070 (approx. 5.3% of US population)
- New Cases (7 day average) = 220,690
- Percentage of New Global Cases = 34.4%
- Percentage of positive tests (7 day average) = 14.9%
- Record high 7 day average of new cases
- During the last 30 days, the 7 day average has increased from 161,618 to 220,690, an increase of 36.6%, which translates into an annualized increase of 439.2% (!!)
- More than one-third of reported global cases
- Record high positive test rate
- Total Deaths = 1,667,441 (approx. 0.02% of global population)
- New Deaths (7 day average) = 11,291
- Record high 7 day average of new deaths
- 7 day average is increasing at a rapid rate
- During the last 30 days, the 7 day average has increased from 9,207 to 11,291, an increase of 22.6%, which translates into an annualized increase of 271.2% (!)
- Total Deaths = 317,929 (approx. 0.1% of US population)
- New Deaths (7 day average) = 2,599
- Percentage of Global New Deaths = 23%
- Second highest number of new cases (3,278), the highest number was on 12/16
- 7 day average of new deaths is increasing at a rapid rate
- During the last 30 days, the 7 day average has increased from 1,200 to 2,599, an increase of 116.6%, which translates into an annualized increase of 1,399.2% (!!!!)
3. Top 5 States in Cases, Deaths, Hospitalizations, Patients in ICU & Positivity (12/17)
- After declining to a low of 13.4% on 12/11, the US Positivity Rate reached an all-time high of 14.9%.
- Overall, 32 states reported lower positivity rates over the last seven days (+7 states since 12/11).
- After 46 straight days above 50.0% positivity, ND declines to 38.2%.
- Four states (ID, NV, SD, PA) 7-day positivity rates greater than 40%. (+2 since 12/11)
- Eleven states (IN, ND, MO, KS, WI, NE, IA, AZ, UT, AL, WY) 7-day positivity rates greater than 30%. (-1 since 12/11)
- Nine states (RI, CO, NH, DE, TN, MN, FL, MA) had 7-day positivity rates greater than 20%. (+2 since 12/11)
- In total, 47 states have 7-day positivity rates greater than 5% (Unch since 12/11)
- Hospitalizations in the US reached an all-time high of 114,237, up 6.5% since a week ago. Hospitalizations are increasing, but the rate of growth is slowing. The growth rate on 12/11 was 6.75%.
- 23 states have had increases of hospitalized patients of more than 10% since 11/29. (+6 since 12/10)
- 31 states have more than 1,000 hospitalized patients (-1 since 12/10)
- 24 states saw decreases in the number of hospitalized patients over the past week. (+2 since 12/10)
Patients in ICU Trends
- ICU Patients in the US fell slightly from an all-time high of 21,936 on 12/16 to 21,900 on 12/17. This was an increase from 21,023 (+4.2%) a week ago. The number of ICU patients continues to increase, but the rate of growth is slowing. The growth rate on 12/10 was 6.6%.
- 15 states have seen the number of ICU patients increase by more than 10% since a week ago (Unchanged since 12/10)
- 31 states have more than 100 patients in ICU, (+1 since 12/10)
- 16 states saw decreases in the number of ICU patients over the past week (Unchanged since 12/10).
4. U.S. Sets Records for Newly Reported Infections, Deaths
What to Know
- An FDA panel recommended Moderna’s C19 vaccine for emergency-use authorization at a hearing today.
- Intensive-care unit capacity in Southern California hit 0%.
- The U.S. reported more than 247,000 new coronavirus cases.
- The number of deaths from C19 in a single day reached an all-time high. Hospitalizations also set another record.
- French President Emmanuel Macron has tested positive for the virus.
- The EU intends to start vaccinations as soon as Dec. 27.
- Italy is debating a lockdown over the holiday period.
- Moderna plans to offer its vaccine to all trial participants who received the placebo.
- A federal vaccine-advisory committee recommended the Food and Drug Administration authorize a second C19 vaccine for broad distribution in the U.S. The FDA is expected to grant authorization by late Friday.
- The panel’s backing of Moderna’s two-dose vaccine comes almost a week after it recommended Pfizer’s vaccine, launching America’s largest vaccination campaign. Doses of the Pfizer-BioNTech vaccine continue to roll out across the country.
- The arrival of a C19 vaccine comes as the pandemic in the U.S. reaches new heights, with the virus widespread in many communities and the holiday season posing fresh challenges for containment. The U.S. on Wednesday logged a record-high number of newly reported C19 cases in a day, at more than 247,000 new infections. The number of people hospitalized with the virus continued to surge, setting a fresh record for the 11th day in a day, while confirmed deaths rose to a record 3,656.
C. New Scientific Findings & Research
1. Safe Social Distancing Alert: Long Streams of Virus-Laden Droplets Can Trail Behind Infected Individuals
Fast walking in narrow corridors can increase C19 transmission risk, especially for children.
- Long streams of virus-laden droplets can trail behind infected individuals walking through a narrow corridor, impacting safe social distancing guidelines.
- Computational simulations have been used to accurately predict airflow and droplet dispersal patterns in situations where C19 might be spread. In the journal Physics of Fluids, by AIP Publishing, results show the importance of the shape of the space in modeling how virus-laden droplets move through the air.
- The simulations are used to determine flow patterns behind a walking individual in spaces of different shape. The results reveal a higher transmission risk for children in some instances, such as behind quickly moving people in a long narrow hallway.
- Previous investigations using this simulation technique have helped scientists understand the influence of objects, like glass barriers, windows, air conditioners, and toilets, on airflow patterns and virus spread. The previous simulations have usually assumed a large, open indoor space but have not considered the effect of nearby walls, like those that might exist in a narrow corridor.
The cough-generated droplets from a walking individual disperse differently in a narrow corridor and an open space. In an open space, the droplets are dispersed in a large range attached to the person.
- If a person walking in a corridor coughs, their breath expels droplets that travel around and behind their body, forming a wake in the way a boat forms a wake in water as it travels. The investigation revealed the existence of a “re-circulation bubble” directly behind the person’s torso and a long wake streaming out behind them at approximately waist height.
- “The flow patterns we found are strongly related to the shape of the human body,” said author Xiaolei Yang. “At 2 meters downstream, the wake is almost negligible at mouth height and leg height but is still visible at waist height.”
- Once the airflow patterns were determined, the investigation modeled the dispersal of a cloud of droplets expelled from the simulated person’s mouth. The shape of the space surrounding the moving person is particularly critical for this part of the calculation.
- Two types of dispersal modes were found. In one mode, the cloud of droplets detaches from the moving person and floats far behind that individual, creating a floating bubble of virus-laden droplets. In the other mode, the cloud is attached to the person’s back, trailing behind them like a tail as they move through the space.
In both modes, the cloud of droplets hovers at about half-height of the infected person before reaching the ground, indicating higher risk for children to inhale the droplets.
- “For the detached mode, the droplet concentration is much higher than for the attached mode, five seconds after a cough,” said Yang. “This poses a great challenge in determining a safe social distance in places like a very narrow corridor, where a person may inhale viral droplets even if the patient is far in front of him or her.”
- The danger is particularly great for children, since in both modes, the cloud of droplets hovers at a distance above the ground that is about half the height of the infected person — in other words, at mouth level for children.
2. Women at less risk of severe disease or death from C19
- Female C19 patients face less severe disease complications and a lower risk of dying than male patients thanks to hormones and chromosomes that contribute to a stronger immune response, according to new research from a University of Alberta-led team.
- “The highlight of our study is how the sex differences in C19 are linked to ACE2,” said senior author Gavin Oudit, professor of medicine in the Faculty of Medicine & Dentistry, Canada Research Chair in Heart Failure and director of the Heart Function Clinic at the Mazankowski Alberta Heart Institute.
- ACE2 is the enzyme that acts as the receptor allowing the coronavirus (SARS-CoV-2) to enter the body, but it is also key in protecting against cardiovascular, lung and kidney diseases.
- “Because of their chromosomes, women have two copies of the ACE2 gene and men have only one copy,” Oudit said. “This does not seem to make women more susceptible to C19 infection, but it does protect them from the complications associated with the virus.”
- Oudit explained that ACE2 is an X chromosome-linked gene. To avoid duplication, one X chromosome tends to be inactivated, but due to its location ACE2 escapes inactivation, meaning women have twice as many active genetic instructions to make ACE2.
- Another gene that is twice as strong in women due to this X-inactivation escape is called Toll-like receptor seven, a key part of the innate immune system.
- “The stronger presence of Toll-like receptor seven in women explains why women’s immune systems are stronger than men’s and can tolerate virus infection better, including the common cold,” Oudit said. “The man-cold phenomenon is real.”
- In the study, the researchers report that men face more severe illness and poorer outcomes around the world, including in Alberta. They note that women likely face more exposure to SARS-CoV-2 than men–for example, 70% of health-care workers are female–but this is not reflected in their outcomes.
- “Due to gender issues, women face more risk, so it’s reassuring to know that their outcomes are not any worse; in fact they are clearly better than men’s,” Oudit said.
- Research is underway to understand how manipulating ACE2 levels might help C19 patients, to prevent infection by blocking the enzyme or to protect the cardiovascular system, lungs and kidneys by enhancing it.
- “We need to look at the factors that are responsible for better outcomes for everyone, taking sex differences into consideration when we test new therapies and provide C19 care,” said Oudit.
3. Patients on ACE inhibitors, ARBs, don’t have higher C19 risk
- While the C19 pandemic left the world searching for answers during the earliest stages of the pandemic, one immediate healthcare concern regarded the use of certain antihypertensives–and whether they posed increased risks to patients with hypertension.
- A new study by global collaborators within the Observational Health Data Sciences and Informatics (OHDSI) community found that there was no increased risk of C19 diagnosis, hospitalization, or subsequent complications for users of either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) among an international cohort of more than 1.1 million patients using antihypertensives.
- The study was published today in The Lancet Digital Health.
- This real-world evidence, generated through open-science approaches, support recent regulatory and clinical recommendations that patients should not discontinue ACE inhibitor or ARB therapy due to concerns of increased C19 risk.
- “People with hypertension have worse C19 outcomes, and there remains speculation that some anti-hypertensive medications may be detrimental,” says corresponding author Marc A. Suchard, a professor at UCLA and research team leader. “The clear answer is that ACE inhibitors and ARBs pose no increased risk as compared to other treatments.”
- While other studies have generated similar findings recently, this study is the most comprehensive to date of C19 susceptibility risks for antihypertensive users. OHDSI researchers examined electronic health records from a trio of data sources from the United States and Spain (Columbia University Irving Medical Center, the Department of Veteran Affairs and the Information System for Research in Primary Care) to conduct a systematic cohort study of ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users.
- The findings also showed no clinical reason to switch from an ARB to an ACE inhibitor to minimize C19 risk.
- “Based on our results, if there is a risk difference, it’s marginal and would be very challenging to further refine outside such a large-scale international study,” Suchard said.
4. Gene Identified That Could Explain Why C19 Causes No Symptoms in Some and Serious Illness or Death in Others
- The Translational Genomics Research Institute (TGen), an affiliate of City of Hope, has identified a specific genetic target that could help explain the tremendous variation in how sick those infected with C19 become.
- The study results, recently published in the journal mSphere, describe a molecule made from DNA — miR1307 — as a potential dimmer switch that may influence the severity of the disease; why some infected with the coronavirus (SARS-CoV-2) C19, have mild or even no symptoms, while others become seriously ill or die.
- Led by Nicholas Schork, Ph.D., a Distinguished Professor and Director of TGen’s Quantitative Medicine and Systems Biology Division, researchers identified miR1307 by comparing the genetic elements of SARS-Cov-2 with seven other human coronaviruses, some of which merely cause common colds. In addition, they examined the genomes of coronavirus strains known to infect bats, pigs, pangolins, ferrets, civets, and chickens.
- “We pursued a systematic gene-by-gene comparative analysis, investigating how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes,” Dr. Schork said. “Our study results will allow the development of models of how the virus and its hosts interact, enhancing our understanding of the disease-causing mechanisms of SARS-CoV-2 and how to exploit both viral and host therapeutic targets.”
- Study results suggest that miR1307 serves as a switch that turns various genes within the virus on or off, potentially making the disease more or less harmful to patients by regulating, for example, how fast or slow the virus replicates. In past studies, miR1307 has been found to affect the severity of several types of cancer, lung disease, and the flu, specifically the H1N1 influenza virus that caused a 2009 pandemic. It was first discovered as a key regulatory agent in the Epstein-Barr virus, best known as the cause of infectious mononucleosis.
- According to Dr. Schork, the study results also provide the basis for additional investigations, such as designing vaccines based on proteins or RNA, developing specific genetic markers for community disease monitoring, and tracing C19 from one species to another.
5. Four genetic variants are linked to severe C19
- Certain gene variants are linked to severe coronavirus infections, according to a team of scientists in Europe who studied the genomes of 2,200 critically ill C19 patients. Their results provide robust support that genetic makeup plays a role in the potentially fatal illness experienced by some people infected by the coronavirus.
- Diving into people’s DNA is an approach that could help answer one of the pandemic’s biggest mysteries: Why do some people have mild coronavirus cases, or no symptoms at all, while others rapidly fall ill and die? Evidence is clear that older age and underlying conditions are risk factors for increased C19 severity. But genetic predispositions to runaway inflammation or other harmful immune responses could also contribute to worse disease.
- Knowing this, researchers are working to uncover genes closely linked with biological systems to accelerate drug development for C19.
- “Our primary aim in this work is to find effective treatments,” said study author Kenneth Baillie, a University of Edinburgh clinical researcher and an investigator with the GenOMICC Consortium, which explores associations between genes and critical illness.
- Baillie and his colleagues pinpointed eight spots on chromosomes — five of which strongly held up under further scrutiny — where variants were more common among people in intensive care. Some of the genes contain instructions for anti-viral components of the immune system, suggesting flaws in a person’s microscopic defenses that therapeutics might fix, at least in theory.
- “Looking across thousands of people, there are little variations in how much there is of each signal; these variations arise because of genetic differences between people,” Baillie said. “At this scale, we can see the effect of these variations, so we can directly predict the effect of drugs that hit the immune system in the same place.”
- Translating results from these types of investigations into successful therapies has, generally, been a struggle. The process often requires lengthy research even before drugs are ready to be tested in people.
- “There is no guarantee that when a gene is found, targeting that gene will result in therapeutic efficacy,” said Tom Hemming Karlsen, a physician at the University of Oslo who did not participate in the new work. He added: “What genetics studies like this then do is they help us find very specific starting points” for further investigation.
- In what’s known as a genome-wide association study, Baillie and his colleagues examined the genes of more than 2,000 C19 patients in intensive care units across Britain, and compared those with the genes of healthy people. The research, published recently in the journal Nature, aligns with earlier reports that also found variants in the genetic makeup of critically ill patients.
- The new report is the “biggest published to date of its kind,” Karlsen said. He is a co-author of a paper, published earlier this year in the New England Journal of Medicine, which used the same scientific process to identify gene variants associated with severe C19.
- That study found people with blood type A were at higher risk of severe infections, while having blood type O was somewhat associated with a protective effect. It also noted a location on chromosome 3 linked to respiratory failure.
- The new work detected the link to chromosome 3, too, though how that cluster relates to severe C19 is not clear. What’s more, “several of the new findings are able to point quite directly to genes with known functions of relevance to the immune system or antiviral responses,” Karlsen said.
- Among the new links to severe disease is a gene named IFNAR2. That gene allows cells to build a protein receptor for a potent immune molecule, dubbed interferon for its ability to interfere with viral replication. It is part of the body’s first responses against infection. But a weak interferon response could allow the virus to quickly proliferate. That, in turn, may result in a potentially deadly overcorrection when later immune defenses kick in.
- The study reveals “genetic variants, particularly near genes that are involved in the so-called interferon immune response play an important role in causing a life-threatening C19 infection,” said Lude Franke, a statistical geneticist at the University of Groningen, who was not involved in the Nature report.
- Experts cautioned these types of investigations rarely produce evidence for direct cause-and-effect relationships between specific genes and disease severity or susceptibility to infection.
- “A chunk of the answer is in our genes” but “it’s unlikely that a single element is fully responsible for the development of severe C19,” study author Sara Clohisey, a researcher at the University of Edinburgh, pointed out. “It’s more likely to be a combination of factors,” she said, which may include genetics as well as age, obesity, gender and other characteristics. (Although men are more likely to die of coronavirus infections than women, the scientists did not detect genetic variants linked to sex in this study.)
- Yet Baillie said this work provides “causal evidence,” specifically for the IFNAR2 gene, and another, called TYK2, that “the products of those genes change a person’s chance of becoming critically ill with covid.”
- Karlsen said “very rare, but more deleterious genetic variants in the same genes, may provide a stronger driver towards severe disease, as seen for IFNAR2.”
- Interferon has been tested as a possible C19 therapy in clinical trials, although one large trial found giving interferon to hospitalized patients did not reduce mortality. The study authors also noted that the anti-inflammatory drug baricitinib, used to treat rheumatoid arthritis and being tested in C19 patients, can inhibit the protein encoded by the TYK2 gene.
- The researchers plan to continue to analyze DNA samples from coronavirus patients — not only those who were severely ill and in intensive care, but also from people who had milder symptoms.
- There’s no shortage of potential donors as the outbreaks continue. “The pandemic is still raging,” Clohisey said. Since they began writing this paper, she said, the researchers have tripled their DNA samples of people who have had the coronavirus.
6. Researchers Uncover Evidence That UV Radiation From Sunlight Reduces C19 Transmission
- Scientists, policymakers, and healthcare workers are eager to discern to what extent C19 may be seasonal. Understanding this aspect of the disease could guide our response to the pandemic.
- Researchers at UC Santa Barbara have found evidence that the spread of C19 is sensitive to UV exposure. While this suggests that C19 may vary with the seasons, there are other seasonal factors — such as temperature, specific humidity and precipitation — whose effects are uncertain given the available data. The results appear in the Proceedings of the National Academy of Sciences.
- “Related species of coronavirus — like SARS from 2003 and MERS from 2012 — turned out to have weak relationships with temperature and humidity, but were sensitive to UV radiation,” said coauthor Kyle Meng, an environmental economist in UC Santa Barbara’s economics department and at the campus’s Bren School of Environmental Science & Management.
- Meng, together with Tamma Carleton, also at the Bren School, Peter Huybers and Jonathan Proctor from Harvard, and Jules Cornetet at France’s École Normale Supérieure Paris-Saclay, sought to explore the relationship between UV radiation and the spread of C19 by constructing a high-resolution global dataset of daily C19 cases.
- Many papers compare different locations to get a sense of how the disease reacts to various environmental conditions. But this approach introduces a host of potentially confounding factors into statistical models, such as health care quality, income and cultural norms.
- Meng offers the more temperate United States and more tropical Brazil as examples. “The U.S. and Brazil are different for all kinds of reasons,” he said. “They have different economic conditions and institutions in addition to different environmental conditions.” These distinctions, he said, prevent a clean comparison of the spread of C19 based solely on environmental conditions.
- To circumvent this issue, the team conducted a longitudinal study, essentially comparing many populations to themselves over time. So, rather than compare Brazil to the U.S., they would compare communities within Brazil to themselves at a different time, when local environmental conditions changed. “We basically ask whether daily fluctuations in environmental conditions experienced by a population affect new C19 cases up to two weeks later,” Meng explained.
- The team found evidence that a location’s UV exposure significantly affects C19 transmission. A change in UV exposure by 1 standard deviation (roughly equal to the difference in UV between May and June in Los Angeles) reduced the growth rate of new cases by around 1 percentage point over the following two weeks. That could bring down C19 growth rates from an average daily increase at the beginning of the epidemic of 13% to a 12% increase per day.
- Based on the expected seasonal changes in UV radiation, the model predicted growth rates would increase by 7.3% points for southern temperate locations between January and June. Meanwhile, northern temperate regions would see a UV-driven decrease of 7.4% points during that same period, as longer days increased UV exposure.
- This pattern switches as the seasons flip. By December, the researchers predicted C19 growth rates could decrease by 7.7% in southern temperate regions, compared with July numbers, while cooler northern areas could see a jump of 7.8% over this period.
- Importantly, the seasonal influence of UV on transmission of the disease is small relative to that of social distancing policies such as travel bans, school closures or home isolation, the authors noted. Regardless of the weather, social distancing measures appear to be necessary to substantially slow the spread.
- Conforming with these findings, infection rates appear to have decreased in the northern hemisphere during the summer, possibly due to increased UV exposure. However, much of the northern hemisphere also relaxed their COVID stay-at-home orders at the same time, Meng said. As a result, there’s a conflation between UV effects and the loosening restrictions during the summer months. “This is a big reason why our study uses daily fluctuations in UV exposure, in part to avoid conflating influences when looking at long-term, varying fluctuations.”
- These findings are consistent with concerns about the surge of C19 infections currently being experienced in the U.S. with the arrival of winter; however, to get the full seasonality picture, researchers will need more precise estimates of how the disease responds to other seasonally varying environmental conditions, such as temperature and specific humidity. “We are confident of the UV effect, but this is only one piece of the full seasonality picture,” Carleton said.
- Lab studies will ultimately be critical in determining the mechanisms at work, though the authors suspect multiple factors may be behind the effect of UV on C19 transmission, some of which cannot be studied in the lab. The first is biological. UV can damage the nucleic acids that the virus uses to encode its genetic information. Coauthor Jonathan Proctor, a post-doctoral fellow at Harvard, posited that UV radiation may inactivate the virus as it is being transmitted, such as when it’s suspended in the air or resting on an exposed surface. “Just as UV can destroy our own DNA if we don’t use sunscreen, UV can damage the C19 virus,” Proctor said.
- Another component is behavioral. For example, people may go out more often when it is sunnier, which could alter the risk of transmission. While laboratory studies can help determine the biological mechanisms, population-level studies like this one are able to also capture social factors.
- “In the context of all this, our study suggests that seasonal changes in UV may influence C19 transmission in the coming months,” Meng said. “And if that’s true, we need to think carefully about how to modulate C19 containment policies in a seasonal manner.”
7. Ferrets, Cats, Civets, and Dogs Most Susceptible to Coronavirus Infection After Humans
- Humans, followed by ferrets and to a lesser extent cats, civets and dogs are the most susceptible animals to coronavirus (SARS-CoV-2) infection, according to an analysis of ten different species carried out by researchers at the Centre for Genomic Regulation (CRG), based in Barcelona.
- The findings, published in PLOS Computational Biology, found that ducks, rats, mice, pigs and chickens had lower or no susceptibility to infection compared to humans.
- “Knowing which animals are susceptible to SARS-CoV-2 helps us prevent building up animal reservoirs from which the coronavirus can re-emerge at a later date,” says Luis Serrano, ICREA Research Professor, Director of the CRG and senior author of the study. “Our findings offer a clue for why minks – which are closely related to the ferret – are being infected by the disease, which is probably made worse by their packed living conditions and close contact with human workers.”
The binding affinity for the ACE2 receptors with the spike protein of SARS-CoV-2 across eight different species compared to humans (the blue baseline). Species above the threshold are vulnerable to letting the coronavirus enter the cell while those below have significantly lower or no risk for infection.
- “Though we also find a potential susceptibility to infection by cats, they don’t co-exist with humans in the same conditions as other animals, which may explain why so far there are no known cases of people being infected by their pets,” adds Dr. Serrano.
- Ten species were studied in this paper. Five species – humans, cats, ferrets, civets, and dogs – have had documented cases of infection by SARS-CoV-2. There are no reports of infection in the other five species – mice, rats, pigs, chickens, and ducks.
- The researchers used computer modeling to test how the coronavirus uses its spike proteins, which protrude from the surface of the virus, to infiltrate the cells of different animals. The main point of entry on a cell’s surface is the ACE2 receptor, which binds with the spike protein through a lock-and-key mechanism. There are many different variants of ACE2 within human populations and across different species.
- Variants of the ACE2 receptor in humans followed by ferrets, cats, dogs, and civets have the highest binding affinities to the viral spike protein, while mice, rats, chicken, and ducks have poor binding energy.
- However, binding affinity is not enough on its own to gauge a cell’s susceptibility to infection. The researchers also tested the different species’ ‘codon adaptation index’ – which is how efficient the coronavirus is at commandeering a cell’s machinery once it has entered. The more efficient the process, the better the coronavirus can create the proteins it needs to replicate.
- Humans, chickens, and ducks have the highest codon adaptation index, while the other species are worse adapted.
- Considering both binding affinity and the codon adaptation index, the researchers conclude that humans, followed by ferrets, cats, civets and dogs are the most susceptible animals to infection by coronavirus.
- They also found that different human variants of ACE2 showed differences in stability and binding to the spike protein, a sensitivity that may underlie why some people suffer from severe C19 symptoms.
- “We have identified mutations on the S-protein that dramatically reduces the capacity of SARS-CoV-2 to enter into the cell, protecting the host from catching C19,” says Javier Delgado, researcher at the CRG and first author of the study. “We are now engineering mini-proteins from the human ACE2 protein to ‘distract’ the attention of the virus from entering cells and block an infection. Should new mutations of the viral spike protein arise, we could engineer new variants to block them.”
- Understanding SARS-CoV-2 infectivity across different species can better inform public health measures, helping reduce human contact with other susceptible animals and avoiding the potential prolongment of the C19 pandemic.
- According to the WHO, since June 2020, 214 human cases of C19 have been identified in Denmark with SARS-CoV-2 variants associated with farmed minks, including 12 cases with a unique variant, reported on November 5. Preliminary findings indicate that this particular mink-associated variant has moderately decreased sensitivity to neutralizing antibodies – though this has not been demonstrated.
D. Vaccines & Testing
1. A C19 Vaccine Playbook: What to Expect and When (Taking Effect, Duration, Returning to Normal Life)
- As the CDC begins to schedule the vaccine rollout, there are so many questions.
- What can the public expect from a vaccination? Will we still have to be cautious about social contact and wear masks? How long before immunity kicks in? When will life return to normal?
- Northwestern Medicine infectious disease and critical care experts offer a vaccine playbook below.
How long does it take for the COVID vaccines to take effect?
- “All but one of the COVID vaccines in phase 3 clinical trials require two injections a few weeks apart. Then it will take a few weeks to obtain the full protective effect. Vaccines generate an immune response that mimics someone getting infected with the virus itself. It takes weeks for a full protective response during which the body makes antibodies and long-lasting memory T cells that can rapidly respond if the vaccinated person encounters the virus to protect them.” – Dr. Benjamin Singer
- After vaccines become widely available, will we still have to be cautious? Wear masks? Social distance?
- “I anticipate that masking and social distancing will be required for some time. Vaccines will take time to become widely available and take effect. Moreover, we may not see widespread vaccination of the population without concerted public health efforts on a national level. Note that adult vaccination rates for seasonal influenza rarely reach 50%.” – Singer
- “We will need some level of protection until everyone is able to be vaccinated and the case prevalence reaches levels able to be controlled with contact tracing. Other factors, including how many people get vaccinated and how the virus is spreading in communities, will also affect our behaviors.” – Dr. Michelle Prickett
- “When everyone who wants a vaccine has received a vaccine, and the proportion of people either vaccinated or who had C19 reaches a “herd immunity” threshold, we won’t need masks or social distancing any longer. Until we get to that point, we will have to follow the guidance of our public health officials and continue to wear masks and practice social distancing.” – Dr. Robert Murphy
How much will vaccine compliance affect our safety and return to normal life?
- “The vaccine appears to be very effective in preventing C19. In addition, the few trial subjects who received the vaccine but still contracted C19 had only mild illness.” – Singer
Will we need to get a new C19 vaccine every year like the flu vaccine? If so, why?
- “Recommendations for repeat vaccination will depend on the observed duration of protection as participants from vaccine clinical trials are followed over time.” – Singer
- “We are not expecting to have a different vaccine annually with the coronavirus (SARS-CoV-2). If the virus were to mutate and become resistant to one or more of the vaccines, then we would have to change to a different vaccine with a different target.” – Murphy
When might a normal life as we knew it — pre-COVID — resume?
- “If vaccines are widely available by the spring, and there is a distribution plan, I would imagine we could expect the restrictions to ease and return to normal by mid to late summer.” – Prickett
- “In the latter half of 2021, things will be very different and much better than now, however a pre-covid state is more likely in 2022.” – Murphy
When will the “average” person, not high risk, be able to take the vaccine?
- “As production ramps up and distribution networks are developed, the vaccines will become available to anyone who wants to take them. That should occur sometime mid-year 2021. Still, it will take many months to vaccinate those that want it as logistically, it will be challenging.” – Murphy
Does a person who has been infected with C19 still need to get the vaccine?
- “Patients who have been infected with C19 should still get the vaccine. We are not certain that a prior infection will lead to lifelong immunity. Current data suggests a prior infection could confer immunity for around six months.” – Prickett
- Dr. Michelle Prickett is an associate professor of medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine pulmonary and critical care specialist.
- Dr. Robert Murphy is executive director of the Institute for Global Health at Feinberg and Northwestern Medicine infectious disease expert.
- Dr. Benjamin Singer is assistant professor of medicine at Feinberg and a Northwestern Medicine pulmonary and critical care specialist.
2. What are the ingredients of Pfizer’s C19 vaccine?
- What’s actually on the official ingredient list? This week an elderly UK woman became the first person outside of a trial to get the newly approved vaccine developed by Pfizer and BioNTech, and the US could greenlight the same inoculation as soon as Thursday, December 10. Along with the regulatory actions over the last week have come the most detailed disclosures yet of the new vaccine’s makeup.
- Here is what the US Food and Drug Administration says is in Pfizer’s vaccine:
- nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2
- (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis (ALC-3015)
- (2-hexyldecanoate),2-[(polyethyleneglycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
- 1,2-distearoyl-snglycero-3-phosphocholine (DPSC)
- potassium chloride
- monobasic potassium phosphate
- sodium chloride
- basic sodium phosphate dihydrate
- Reading the ingredient list is like looking at the side of a cereal box, except that you need a degree in organic chemistry to understand it. We got help from various scientists and biotech entrepreneurs to understand what each of the ingredients does and make some educated guesses about others.
- Pfizer’s vaccine is the first on the market that consists of actual genetic information from a virus in the form of messenger RNA, or mRNA, a type of molecule whose usual job is to transport copies of genetic instructions around a cell to guide the assembly of proteins. Imagine an mRNA as a long ticker tape carrying instructions. It’s fairly delicate stuff, and that’s why Pfizer’s vaccine needs to be kept at around -100 °F (-73 °C) until it’s used.
- The new vaccine, delivered as a shot in the arm muscle, contains an RNA sequence taken from the virus itself; it causes cells to manufacture the big “spike” protein of the coronavirus, which the pathogen uses to glom onto a person’s cells and gain entry. On its own, without the rest of the virus, the spike is pretty harmless. But your body still reacts to it. This is what leaves you immunized and ready to repel the real virus if it turns up.
- The mRNA in the vaccine, to be sure, isn’t quite the same as the stuff in your body. That’s good, because a cell is full of defenses ready to chop up RNA, especially any that doesn’t belong there. To avoid that, what’s known as “modified nucleosides” have been substituted for some of the mRNA building blocks.
- But Pfizer is holding back a little. The spike gene sequence can be tweaked in small ways for better performance, by means that include swapping letters. We don’t think Pfizer has said exactly what sequence it is using, or what modified nucleosides. That means the content of the shot may not be 100% public.
- The Pfizer vaccine, like one from Moderna, uses lipid nanoparticles to encase the RNA. The nanoparticles are, basically, tiny greasy spheres that protect the mRNA and help it slide inside cells.
- These particles are probably around 100 nanometers across. Curiously, that’s about the same size as the coronavirus itself.
- Pfizer says it uses four different lipids in a “defined ratio.” The lipid ALC-0315 is the primary ingredient in the formulation. That’s because it’s ionizable—it can be given a positive charge, and since the RNA has a negative one, they stick together. It’s also a component that can cause side-effects or allergic reactions. The other lipids, one of which is the familiar molecule cholesterol, are “helpers” that give structural integrity to the nanoparticles or stop them from clumping. During manufacturing, the RNA and the lipids are stirred into a bubbly mix to form what the FDA describes as a “white to off-white” frozen liquid.
- The Pfizer vaccine contains four salts, one of which is ordinary table salt. Together, these salts are better known as phosphate-buffered saline, or PBS, a very common ingredient that keeps the pH, or acidity, of the vaccine close to that of a person’s body. You’ll understand how important that is if you’ve ever squeezed lemon juice on a cut. Substances with the wrong acidity can injure cells or get quickly degraded.
- The vaccine includes plain old sugar, also called sucrose. It’s acting here as a cryoprotectant to safeguard the nanoparticles when they’re frozen and stop them from sticking together.
- Before injection, the vaccine is mixed with water containing sodium chloride, or ordinary salt, just as many intravenously delivered drugs are. Again, the idea is that the injection should more or less match the salt content of the blood.
- Pfizer makes a point of saying its mixture of lipid nanoparticles and mRNA is “preservative-free.” That’s because a preservative that’s been used in other vaccines, thimerosal (which contains mercury and is there to kill any bacteria that might contaminate a vial), has been at the center of worries around over whether vaccines cause autism. The US Centers for Disease Control says thimerosal is safe; despite that, its use is being phased out. There is no thimerosal—or any other preservative—in the Pfizer vaccine. No microchips, either.
- The vaccine is still known by the code name BNT162b, but once it’s authorized, expect Pfizer to give it a new, commercial name that conveys something about what’s in it and what it promises for the world.
3. A guide to who can safely get the Pfizer C19 vaccine
- With the first doses of C19 vaccine being administered across the United States, questions abound about who can safely get them.
- Expect answers to those questions to evolve as the vaccines go into broader use. But here’s what is known so far, and what experts at or advising the Centers for Disease Control and Prevention recommend regarding their use at this point.
- The Covid vaccine developed by Pfizer and its partner, BioNTech, hasn’t yet been tested in pregnant people — in fact none of the vaccines in development have been. Drug and vaccine makers are always reluctant to include pregnant people in clinical initial trials for fear of injuring a developing fetus or threatening a pregnancy.
- For now, the CDC’s assessment is that pregnant people should be offered a chance to get the vaccine, but should informed it hasn’t yet been tested in the population. (Britain’s Joint Committee on Vaccination and Immunization took a different approach, advising against giving the vaccine to pregnant people.)
- During last Saturday’s meeting of the Advisory Committee on Immunization Practices — an expert group that advises the CDC — a Pfizer executive said there were no safety concerns raised in the preliminary data from animal studies conducted to see if the company’s vaccine could pose a risk to developing fetuses. This type of animal study, called a developmental and reproductive toxicity trial, is a prerequisite to testing the vaccine in pregnant people.
- To date the vaccine’s safety in those who are lactating hasn’t been studied. So there are no data on which to advise whether they should be vaccinated.
- On the other hand, messenger RNA vaccines — the Pfizer and Moderna vaccines are both mRNA vaccines — are not thought to pose a risk to a breastfeeding infant, the CDC said, indicating that if those who are lactating are in a priority group eligible for vaccination, they can choose to be vaccinated if they wish.
People with allergies
- Reports that two nurses in Britain developed anaphylaxis after being immunized with the Pfizer vaccine last week triggered concerns about whether people with allergies should be vaccinated. Both the women had serious allergies and carried EpiPens.
- The CDC’s clinical guidance, which the agency posted to its website on Monday, is broken down into three categories — proceed with vaccination, vaccinate with caution, and don’t vaccinate.
- People who have allergies to foods, animals, insects, latex, and other common allergies can be vaccinated. Likewise, people with allergies to oral drugs, even if they are the oral equivalent to an injectable drug, can take the vaccine, the CDC guidance said. Included in this group are people who have had a non-serious allergic reaction to an injection — though not anaphylaxis — and people who have a family history of anaphylaxis, but who have not experienced it themselves.
- People who have had a severe allergic reaction to a vaccine or an injectable therapy can be vaccinated, but with caution. These people should undergo a risk assessment with their care provider.
- People who have a severe allergic reaction to a dose of this vaccine should not receive another dose, the Food and Drug Administration’s fact sheet on the vaccine said. And people who have a history of a severe allergic reaction to any of the components of the Pfizer vaccine should not be vaccinated with it, the CDC guidance said.
- The vaccine consists of messenger RNA and four lipid nanoparticles; there are no preservatives in the vaccine. In a call with physicians on Sunday, a CDC scientist said people could be allergic to a part of the lipid nanoparticle known as polyethylene glycol, or PEG, which is a component in other injectable medicines. A detailed list of the ingredients in the vaccine is on page 2 of the FDA fact sheet linked to above.
Children and teens younger than 16
- The Pfizer vaccine was authorized for use in people 16 years of age and older. While the company is now studying its use in adolescents aged 12 to 15, data from that work were not part of the company’s application to the FDA for an emergency use authorization. So for now, the vaccine isn’t authorized for use in anyone below the age of 16.
- Studies in children 11 and under will require what’s known as dose de-escalation — figuring out how much vaccine is appropriate and tolerated in younger children. That work hasn’t started yet.
People with HIV
- Pfizer enrolled some HIV-positive volunteers with stable infections in its Phase 2/3 clinical trial, but there are not enough data to date to do an analysis of this population.
- The CDC said people with HIV can be vaccinated, but should be counseled that the safety and efficacy of the vaccine in immunocompromised people is still unclear and they should continue to take other measures to protect themselves against infection.
People on immunosuppressant therapy
- People who take drugs to suppress their immune systems — organ recipients, for instance — can be vaccinated as long as they don’t have another condition for which vaccination is not advised.
People who have recently received or plan to soon receive another vaccination
- Co-administration of vaccines is common, and a useful tool for vaccine delivery. It’s easier to give someone two shots at once than to ask them to come in twice. If it turns out people need regular Covid vaccine boosters, for instance, it’s likely they would be administered when people get their flu shots.
- But in order to be sure vaccines can be co-administered without undermining the effectiveness of any of the vaccines, studies need to be conducted, and there hasn’t been time. So for now the CDC is recommending that people not get any other vaccinations in the two weeks before or two weeks after getting a Covid vaccine.
- That said, if someone inadvertently gets the Pfizer vaccine less than two weeks after getting another immunization, they do not need to repeat either vaccination, the CDC said.
People who got the Pfizer vaccine for their first C19 shot
- Anyone who gets a first dose of the Pfizer vaccine needs to get the Pfizer vaccine for their second shot 21 days later. (Actually, the shot can be given within a 17-day to 21-day window.)
- The same will be true of the Moderna vaccine, which will likely receive an emergency use authorization later this week.
- At some point in time, research may show Covid vaccines can be used interchangeably. But until the issue is studied, the vaccines need to be used as authorized. No getting the Pfizer vaccine for the first dose and the Moderna the second, or vice versa.
4. Phase III Clinical Trial Success: Oxford C19 Vaccine Is Safe and Protects Against Disease
- Interim results of the Oxford C19 vaccine trials find that the vaccine protects against symptomatic disease in 70% of cases — with vaccine efficacy of 62% for those given two full doses, and of 90% in those given a half then a full dose (both trial arms pre-specified in the pooled analysis). The results are the first full peer-reviewed efficacy results to be published for a C19 vaccine, and are published in The Lancet.
- The vaccine was found to be safe, with only three out of 23,745 participants over a median of 3.4 months experiencing serious adverse events that were possibly related to a vaccine; one in the vaccine arm, one in the control arm, and one in a participant who remains masked to group allocation. All participants have recovered or are recovering, and remain in the trial.
- Study author, Dr. Merryn Voysey, University of Oxford, UK, says: “The results presented in this report provide the key findings from our first interim analysis. In future analyses, with more data included as it becomes available, we will investigate differences in key subgroups such as older adults, various ethnicities, doses, timing of booster vaccines, and we will determine which immune responses equate to protection from infection or disease.”
- Study lead author Professor Andrew Pollard, University of Oxford, UK, says: “Control of the pandemic will only be achieved if the licensing, manufacturing and distribution of these vaccines can be achieved at an unprecedented scale and vaccination is rolled out to those who are vulnerable. Our findings indicate that our vaccine’s efficacy exceeds the thresholds set by health authorities and may have a potential public health impact.”
- The Oxford C19 vaccine uses a chimpanzee adenovirus viral vector that cannot cause disease in humans and expresses the coronavirus (SARS-CoV-2) spike protein. This means the vaccine delivers the spike protein genetic code into vaccinated people’s cells, which then produce the protein, and teaching the immune system to recognise and attack the virus. Past trial results have found that the vaccine induces antibody and T cell immune responses, and is safe in adults aged 18 years and over, including older adults.
- The authors used the numbers of cases of symptomatic and asymptomatic infection to determine vaccine efficacy.
Vaccine efficacy against symptomatic C19 disease
- The primary outcome of the study was to determine how many cases of symptomatic C19 disease (confirmed by positive test, and the participant having a fever, cough, shortness of breath, or loss of smell or taste) there were in participants who had received two doses of the vaccine (with the first dose being either low or standard dose, and the second dose being standard dose), compared with controls. Only cases that occurred 14 days after the second vaccination had been given were included (11,636 participants in the UK and Brazil trials).
- There were 131 cases of symptomatic C19 disease more than 14 days after the second vaccine dose in these 11,636 people. This included 30/5,807 (0.5%) cases in the vaccine group and 101/5,829 (1.7%) cases in the control group, which equates to a vaccine efficacy of 70%.
- “In order to assess vaccine efficacy, we need to have a sufficient number of C19 cases among participants to indicate that the vaccine is protecting them from disease. Since recruitment of older adults started later than in younger adults there has been less follow up time for these cohorts and less time to accrue C19 cases. This means we have to wait longer to have sufficient data to provide good vaccine efficacy estimates in smaller subgroups.” says Dr Voysey.
- The trial also measured protection against asymptomatic infection by asking 6,638 UK participants to complete weekly COVID tests. However, it is important to note these data are secondary outcomes and findings need to be confirmed when there is more data available from the trial.
- There were 69 cases of asymptomatic C19 disease identified in the UK study’s weekly C19 testing of 6,638 people. This included 29/3,288 (0.9%) cases in the vaccine group, and 40/3,350 (1.2%) cases in the control group, leading to a vaccine efficacy against asymptomatic transmission of 27%.
Protection against severe disease
- Cases of severe disease and hospitalization were monitored for in all 23,745 participants. From 21 days after the first dose there were 10 cases hospitalized for C19, all in the control arm, and two were classified as severe, including one death. These are also secondary outcomes and will require additional confirmation.
- Co-author, Professor Sarah Gilbert, University of Oxford, UK, says: “Despite global spread of C19, a large proportion of the population in many countries have not been infected and are not immune. Vaccines may play an important role in increasing immunity, preventing severe disease, and reducing the health crisis, so the possibility that more than one efficacious vaccine may be approved for use in the near future is encouraging. Here we have shown for the first time that an adenoviral vectored vaccine — a type of vaccine technology which has been in use since 2009 — is efficacious and could contribute to disease control in the C19 pandemic.”
- The authors note that they are not yet able to assess duration of protection, as the first trials were initiated in April 2020 and all disease episodes have accrued within six months of the first dose being administered. Further evidence will be required to determine duration of protection and the need for additional booster doses of vaccine.
- Writing in a linked Comment, Dr. Maria Deloria Knoll and Dr. Chizoba Wonodi, Johns Hopkins Bloomberg School of Public Health, USA (who were not involved in the study), say:
- “Oxford-AstraZeneca’s US$2-3 per dose agreement with the COVAX facility holds good promise for equitable access for LMICs, compared with the high cost of the two mRNA vaccines that have also reported more than 90% efficacy.
- The ChAdOx1 nCoV-19 vaccine can also use routine refrigerated cold chain, which is important since the ultra-low temperature freezers required to store mRNA vaccines could be unaffordable and impractical in many countries and in settings such as nursing homes.
- However, other challenges with any two-dose regimen will exist in many Low and Middle Income Countries (LMICs) where platforms to easily identify, locate, and reach — twice — adults targeted for vaccination are lacking. If the two vaccine injections require different doses, this will add complexity for health workers with little formal training, but can be managed with innovative packaging and proper change management to reduce errors.
- Efficacy is an important consideration, but so are pragmatics of delivery, community acceptance, longevity of effect, whether a vaccine reduces infection and transmission as well as disease, efficacy in high-risk groups, and, of course, safety.
- Despite the outstanding questions and challenges in delivering these vaccines, it is hard not to be excited about these findings and now the existence of three safe and efficacious C19 vaccines, with 57 more in clinical trials.
5. FDA approves first over-the-counter C19 test that delivers near-instant results
- The FDA on Tuesday approved the first over-the-counter C19 test involving a nasal swab — and near-instant results.
- “By authorizing a test for over-the-counter use, the FDA allows it to be sold in places like drug stores, where a patient can buy it, swab their nose, run the test and find out their results in as little as 20 minutes,’’ said Stephen Hahn, commissioner of the FDA, in a statement on the agency’s website.
- “Today’s authorization is a major milestone in diagnostic testing for C19,” Hahn said.
- The agency has already approved more than 25 at-home consumer coronavirus tests — but until now, the collected samples had to be sent away to a lab for results.
- The diagnostics company Ellume makes the new completely at-home test.
- There are drawbacks to it, but its development is still a major step in diagnosing the virus, said Jeff Shuren, the FDA’s director of its Center for Devices and Radiological Health.
- “This test, like other antigen tests, is less sensitive and less specific than typical molecular tests run in a lab,” Shuren said in the release. “However, the fact that it can be used completely at home and return results quickly means that it can play an important role in response to the pandemic.”
E. Improved & Potential Treatments
1. New Research Shows Remdesivir Is Likely a Highly Effective Antiviral Against C19
- The drug remdesivir is likely to be a highly effective antiviral against the coronavirus (SARS-CoV-2), according to a new study by a team of UK scientists. Writing in Nature Communications, the researchers describe giving the drug to a patient with C19 and a rare immune disorder, and observing a dramatic improvement in his symptoms and the disappearance of the virus.
- The response to the C19 pandemic has been hampered by the lack of effective antiviral drugs against SARS-CoV-2. Scientists had pinned hope on the drug remdesivir, originally developed to treat hepatitis C and subsequently tested against Ebola. However, results from large clinical trials have been inconclusive, and in early October the World Health Organization (WHO) announced that the drug did not significantly reduce mortality rates. The question is more complicated, however, and a clinical team have now used a different approach to determine the effects of the drug on C19 in a closely monitored patient.
- Dr. James Thaventhiran from the MRC Toxicology Unit at the University of Cambridge said: “There have been different studies supporting or questioning remdesivir’s effectiveness, but some of those conducted during the first wave of infection may not be optimal for assessing its antiviral properties.
- “Mortality is due to a combination of factors, likely including unchecked viral replication and, importantly, the response of the immune system. A clinical trial that looks only at remdesivir’s impact on mortality will have difficulty distinguishing between these two factors. This limits our ability to ask the simple question: how good is remdesivir as an antiviral?”
- To answer this question, a team led by scientists at the University of Cambridge and Barts Health examined the case of a 31 year old man with XLA, a rare genetic condition that affects the body’s ability to produce antibodies and hence fight infection.
- The patient’s illness began with fever, cough, nausea, and vomiting, and on day 19 he tested positive for SARS-CoV-2. His symptoms persisted and on day 30 he was admitted to hospital, where he was given supplemental oxygen due to breathing difficulties.
- Unusually, his fever and inflammation of the lungs persisted for longer than 30 days, but without causing severe breathing problems or spreading to other organs. The researchers say this may have been due to his inability to produce antibodies — although antibodies fight infection, they can also cause damage to the body and even lead to severe disease.
- At first, the patient was treated with hydroxychloroquine and azithromycin, which had little effect, and the treatments were stopped on day 34. The patient then commenced a ten-day course of remdesivir. Within 36 hours, his fever and shortness of breath had improved and his nausea and vomiting ceased. Rising oxygen saturation allowed him to be taken off supplemental oxygen.
- This dramatic clinical response was accompanied by a progressive decrease in levels of C-reactive protein (CRP), a substance produced by the liver in response to inflammation. At the same time, doctors saw an increase in the number of his immune cells known as lymphocytes, and chest scans showed that his lung inflammation was clearing. The patient was discharged on day 43.
- A week after discharge, the patient’s fever, shortness of breath and nausea returned. He was readmitted to hospital on day 54 and given supplemental oxygen. He again tested positive for SARS-CoV-2, was found to have lung inflammation, and his CRP levels had increased and his lymphocyte count fallen.
- On day 61, the patient began treatment with a further ten-day course of remdesivir. Once again, his symptoms improved rapidly, his fever dropped and he was taken off supplemental oxygen. His CRP and lymphocyte count normalised. Following additional treatment with convalescent plasma on days 69 and 70, he was discharged three days later and is no longer symptomatic.
- The team found that the patient’s virus levels fell progressively during his first course of remdesivir, corresponding with the improvement in his symptoms. His virus levels increased again, as did his symptoms, when the first course of the treatment ceased, but the effect of the second course of remdesivir was even more rapid and complete. By day 64, he was no longer testing positive for the coronavirus.
- The patient’s inability to clear his infection without antiviral medication is very likely to be due to his lack of antibodies, say the researchers. However, there are other immune cells that contribute to fighting infection, including those known as CD8+ T cells. The team observed that the patient was able to produce CD8+ T cells that responded to the ‘spike protein’ on the surface of the virus — spike proteins give the virus its characteristic crown profile (hence the name coronavirus). While insufficient to clear the infection spontaneously, this likely contributed to the clearance of virus during the second course of remdesivir.
- Dr. Nicholas Matheson from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge added: “Our patient’s unusual condition gave us a rare insight into the effectiveness of remdesivir as a treatment for coronavirus infection. The dramatic response to the drug — on repeated challenge — suggests that it can be a highly effective treatment, at least for some patients.”
- The team further suspect that remdesvir is likely to be most beneficial when administered early in infection, before the virus is able to trigger a potentially catastrophic immune response. They say that the course of their patient’s disease also underscores the important — but often conflicting — roles that antibodies play in protecting us from infection.
- “The fact that our patient was unable to fight off the disease without treatment suggests that antibodies contribute to the control of SARS-CoV-2,” explained Dr. Matthew Buckland from the Department of Clinical Immunology, Barts Health, London. “But this lack of antibodies may also have prevented his C19 from becoming life-threatening, because he had no antibodies to trigger a damaging immune response.
- “All of this suggests that treatments will need to be tailored for individual patients, depending on their underlying condition — for example, whether it is the virus that is causing the symptoms, or the immune response. The extended viral monitoring in our study was clinically necessary because in April 2020 we didn’t know if this drug would be effective. Adopting this approach more widely could further clarify how best to use remdesivir for clinical benefit.”
2. NIH Clinical Trial: Baricitinib Plus Remdesivir Shows Promise for Treating C19
- The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalized with C19, according to clinical trial results published in the New England Journal of Medicine. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
- The clinical trial is the second iteration of the NIH Adaptive C19 Treatment Trial (ACTT-2), a study protocol to evaluate therapeutics for people hospitalized with C19.
- Remdesivir is a broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. Baricitinib was discovered by Incyte and licensed to Eli Lilly and Company, and marketed under the brand name Olumiant. It is approved in more than 70 countries as a treatment for adults with moderately-to-severely active rheumatoid arthritis. Researchers hypothesized that because many severe symptoms of C19 are caused by a poorly regulated inflammatory response, a therapeutic designed to target inflammation could be helpful for patients. The primary results of this study were first announced in September.
- In the study, the combination of baricitinib and remdesivir reduced median time to recovery in hospitalized C19 patients from eight days to seven days. Patients who required high-flow oxygen or non-invasive ventilation during their hospitalization appeared to have had the largest benefit: their median time to recovery was shortened from 18 days to ten days.
- In addition, participants’ conditions at day 15 of the study (as measured by an eight-category ordinal scale which ranked the severity of their condition) was significantly improved when they received the two therapeutics combined. Recipients of the two treatments also had slightly fewer serious adverse effects.
- The researchers caution that comparing this C19 treatment regimen versus those with other therapeutics such as dexamethasone, is difficult without additional comparison studies. These results do appear to show that baricitinib plus remdesivir can benefit some C19 patients and the combination deserves further clinical study, according to the researchers.
F. Concerns & Unknowns
1. Research strongly suggests C19 virus enters the brain
- More and more evidence is coming out that people with C19 are suffering from cognitive effects, such as brain fog and fatigue.
- And researchers are discovering why. The coronavirus (SARS-CoV-2), like many viruses before it, is bad news for the brain. In a study published Dec.16 in Nature Neuroscience, researchers found that the spike protein, often depicted as the red arms of the virus, can cross the blood-brain barrier in mice.
- This strongly suggests that SARS-CoV-2 can enter the brain.
- The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does the same thing as its binding protein, said lead author William A. Banks, a professor of medicine at the University of Washington School of Medicine and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.
- “The S1 protein likely causes the brain to release cytokines and inflammatory products,” he said.
- In science circles, the intense inflammation caused by the C19 infection is called a cytokine storm. The immune system, upon seeing the virus and its proteins, overreacts in its attempt to kill the invading virus. The infected person is left with brain fog, fatigue and other cognitive issues.
- Banks and his team saw this reaction with the HIV virus and wanted to see if the same was happening with SARS CoV-2.
- Banks said the S1 protein in SARS-CoV2 and the gp 120 protein in HIV-1 function similarly. They are glycoproteins – proteins that have a lot of sugars on them, hallmarks of proteins that bind to other receptors. Both these proteins function as the arms and hand for their viruses by grabbing onto other receptors. Both cross the blood-brain barrier and S1, like gp120, is likely toxic to brain tissues.
- “It was like déjà vu,” said Banks, who has done extensive work on HIV-1, gp120, and the blood-brain barrier.
- The Banks’ lab studies the blood-brain barrier in Alzheimer’s, obesity, diabetes, and HIV. But they put their work on hold and all 15 people in the lab started their experiments on the S1 protein in April. They enlisted long-time collaborator Jacob Raber, a professor in the departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and his teams at Oregon Health & Science University.
- The study could explain many of the complications from C19.
- “We know that when you have the COVID infection you have trouble breathing and that’s because there’s infection in your lung, but an additional explanation is that the virus enters the respiratory centers of the brain and causes problems there as well,” said Banks.
- Raber said in their experiments transport of S1 was faster in the olfactory bulb and kidney of males than females. This observation might relate to the increased susceptibility of men to more severe C19 outcomes.
- As for people taking the virus lightly, Banks has a message:
- “You do not want to mess with this virus,” he said. “Many of the effects that the COVID virus has could be accentuated or perpetuated or even caused by virus getting in the brain and those effects could last for a very long time.”
2. Scientists are studying discovery of a new C19 variant
- A new variant of the coronavirus that causes C19 has been identified in the U.K., where scientists are trying to figure out if it spreads faster than other strains of the pathogen following a rapid pickup in infections.
- U.K. Health Secretary Matt Hancock said Monday that more than 1,000 cases of the new strain have been identified in 60 local-government areas and the number of cases is rising fast.
- “Initial analysis suggests this variant is growing faster than the existing variants,” Mr. Hancock told lawmakers in Parliament. He said there is no reason to think the strain causes more severe illness than older variants, or that the new crop of vaccines would be ineffective against it.
- Similar variants of the virus have been detected in other countries in the past few months, and the U.K. has notified the World Health Organization of the finding, Mr. Hancock said.
- A spokesman for Public Health England said scientists are cultivating the newly identified variant in the laboratory to learn more about its transmissibility and other characteristics. How it responds to vaccines “will be one of the things we look at in the next couple of weeks,” the spokesman said.
- Viruses replicate quickly and mutations are common due to tiny errors in copying genetic material, which can accumulate over time, giving rise to new variants that can behave slightly differently to older strains.
- Scientists around the world have since the beginning of the pandemic been tracking these genetic changes. More than 1,000 variants of the virus that causes C19 have been detected so far, from more than 250,000 viral samples, said Babak Javid, associate professor of infectious diseases at the University of California, San Francisco.
- “It’s incredibly common,” he said.
- In a paper published in the journal Cell in July, scientists described a variant that over time displaced an older strain of coronavirus to become the dominant strain in the global pandemic, possibly because it spread more easily from person to person. A paper in Nature in October showed that variant, known as G614, replicated more quickly in animals, but appeared to be just as susceptible to antibodies that target the earlier strain and wasn’t associated with more severe illness.
- Much of Europe’s new wave over the summer, meantime, was traced to outbreaks among agricultural workers living in cramped conditions in Spain’s Catalonia and Aragón regions. Researchers from Switzerland and Spain identified a variant known as 20A.EU1 that from there spread to nearby cities and across Europe by returning tourists.
- The variant was first detected in June and July, and by late October was in a high proportion of virus samples around Europe whose genome sequences were analyzed, including 80% in Spain, 90% in the U.K., 60% in Ireland and 30% to 40% in Switzerland and the Netherlands.
- Chris Whitty, England’s chief medical officer, said at a press conference Monday it isn’t yet clear whether the new variant is more transmissible than earlier variants, or if it is spreading quickly because infections in Britain in general are rising fast.
- The U.K. on Monday tightened public-health measures in London and in some surrounding areas to combat rising coronavirus cases in the region. Testing has identified the new strain to be spreading fast in this area, but the government said the restrictions were related to the speed of the spread, not the fact that a new strain had been identified there.
- The step is one of a number of moves across Europe aimed at restraining ballooning caseloads ahead of Christmas. Germany is due on Wednesday to begin a strict lockdown until at least Jan. 10.
- Dr. Whitty said there is no indication that the newly detected variant is more dangerous than others or that it is harder to detect. He said it does have mutations on the spike protein, which enables the virus to enter cells and which is the focus of many new vaccines. But he said it is unlikely the coronavirus would yet have mutated into a form resistant to vaccination, since so few people have been vaccinated.
- “There are many variants. It just happens that this one has quite a few more mutations than some of the other variants, which is why we’ve taken it a little more seriously,” he said.
3. C19 Attacks Testicles, May Affect Male Fertility
- A new study has revealed that SARS-CoV-2, the virus which causes C19, infects the testicles and likely impacts male fertility. Recall in March we reported that doctors in central Wuhan raised concerns over testicle damage after observing a lowered ratio of testosterone to luteinising hormone (T/LH).
- Now, nine months later, a team of 14 researchers from Wuhan, China have published disturbing evidence from a small sample of patients that C19 not only infects the testicles, but may interfere with sperm production by causing inflammation and ‘massive’ loss in young sperm cells.
- The team’s findings on how C19 infects testicles corroborates the March reporting – namely, the SARS-CoV-2 spike protein binds to ACE2 receptors, which are produced throughout the body, including the seminiferous tubules which carry sperm while it matures.
- “Strikingly, in four of the five cases, GC [germ cell] loss was massive, with only a few GCs left attached to the seminiferous tubules,” reads the study, published Monday in Nature, Cellular & Molecular Immunology. Five C19 patients included in the study were aged 51, 62, 70, 78 and 83 years of age, while control patients were 71, 78 and 80. And though they may lie on the older-end of the curve where male fertility has begun to decline, the control group’s germ cells were “well aligned around the whole seminiferous tubules” compared to the C19 patients.
- “Consistent with the immunohistochemistry results, RT-qPCR showed significantly increased mRNA levels of ACE2 and TMPRSS2 in the testes of all C19 patient compared to control patient testes,” reads the report, which “further supports the hypothesis that SARS-CoV-2 is able to attack testicular cells.” It is unknown how the virus increases ACE2 production in the testes.
- “Collectively, our findings provide direct evidence that SARS-CoV-2 can infect the testis and GCs, indicating the potential impact of the C19 pandemic on spermatogenesis and male fertility.”
- While the study is small with just five participants, the authors write that “further study is essential to reveal the underlying mechanism of SARS-CoV-2 infection of testicular cells and the correlation of testis infection with the clinical course of C19.”
- Perhaps men who have recovered from C19 should have their sperm counts tested?
4. Obese C19 Patients have poor outcomes not driven by inflammation
- Obesity is associated with poor C19 outcomes but a new study suggests this is not due to increased inflammation, but instead may be driven by respiratory issues or other factors.
- Multiple studies suggest those who are overweight or have obesity are more likely to experience invasive mechanical ventilation, intensive care unit (ICU) admission or death. Population-level studies also suggest a higher C19 mortality rate in countries with greater prevalence of obesity. What was not known before was whether patients with obesity had more inflammation, the so-called cytokine storm of COVID.
- According to the researchers, additional factors may explain the unexpected finding of lower inflammatory markers in patients with obesity. “Though definitive reasons for poor C19 outcomes in obesity remain uncertain, patients with obesity are uniquely vulnerable. They may have independent risk factors (type-2 diabetes, hypertension and coronary artery disease) for poor outcomes in C19, conditions that are inflammatory and immune-mediated,” explained Ana Mostaghim, MD, the lead author for the study who conducted the work while an internal medicine resident at Boston Medical Center (BMC).
- In an effort to better understand these potential factors, the researchers compared outcomes and inflammatory markers in patients with and without obesity who were hospitalized with C19 at BMC, a safety-net hospital. They found that body mass index (BMI) greater or equal to 35 was associated with a two-fold increased risk of ICU transfer and a four-fold risk of all-cause mortality; BMI in the 30-34.9 range (Class I obesity) was also associated with increased risk of ICU transfer, but not significantly associated with increased mortality. They also found that patients with obesity had mostly lower inflammatory markers on the first and second hospital days compared to those without obesity.
- “While patients with obesity had worse clinical outcomes than those without obesity in our study, this effect does not appear to be mediated by a higher degree of inflammation,” added Natasha Hochberg, MD, associate professor of medicine at Boston University School of Medicine and an infectious disease physician at BMC. “Patients with obesity are at higher risk of fatty liver disease and greater viral invasion with organ dysfunction may contribute to the increased mortality seen in these patients. Alternately, patients with obesity may have reduced respiratory reserve.”
- The researchers believe further studies are needed to determine whether this decreased inflammatory response persists during hospitalization, whether pro-inflammatory complications are seen less commonly among patients with obesity and whether anti-inflammatory therapy should be utilized differently in patients with obesity.
5. Coronavirus-like particles very sensitive to temperature
- Winter is coming in the northern hemisphere and public health officials are asking how the seasonal shift will impact the spread of the coronavirus (SARS-CoV-2)?
- A new study tested how temperatures and humidity affect the structure of individual SARS-Cov-2 virus-like particles on surfaces. They found that just moderate temperature increases broke down the virus’ structure, while humidity had very little impact.
- In order to remain infectious, the SARS-Cov-2 membrane needs a specific web of proteins arranged in a particular order. When that structure falls apart, it becomes less infectious. The findings suggest that as temperatures begin to drop, particles on surfaces will remain infectious longer.
- This is the first study to analyze the mechanics of the virus on an individual particle level, but the findings agree with large-scale observations of other coronaviruses that appear to infect more people during the winter months.
- “You would expect that temperature makes a huge difference, and that’s what we saw. To the point where the packaging of the virus was completely destroyed by even moderate temperature increases,” said Michael Vershinin, assistant professor at the University of Utah and co-senior author of the paper. “What’s surprising is how little heat was needed to break them down–surfaces that are warm to the touch, but not hot. The packaging of this virus is very sensitive to temperature.”
- The paper published online on Nov. 28, 2020, in the journal Biochemical Biophysical Research Communications. The team also published a separate paper Dec. 14, 2020 in Scientific Reports describing their method for making the individual particle packaging. The virus-like particles are empty shells made from the same lipids and three types of proteins as are on an active SARS-Cov-2 viruses, but without the RNA that causes infections. This new method allows scientists to experiment with the virus without risking an outbreak.
- The SARS-CoV-2 is commonly spread by exhaling sharply, (e.g. sneezing or coughing), which ejects droplets of tiny aerosols from the lungs. These mucus-y droplets have a high surface to volume ratio and dry out quickly, so both wet and dry virus particles come into contact with a surface or travel directly into a new host. The researchers mimicked these conditions in their experiments.
- They tested the virus-like particles on glass surfaces under both dry and humid conditions. Using atomic force microscopy they observed how, if at all, the structures changed. The scientists exposed samples to various temperatures under two conditions: with the particles inside a liquid buffer solution, and with the particles dried out in the open. In both liquid and bare conditions, elevating the temperature to about 93 degrees F for 30 minutes degraded the outer structure. The effect was stronger on the dry particles than on the liquid-protected ones. In contrast, surfaces at about 71 degrees F caused little to no damage, suggesting that particles in room temperature conditions or outside in cooler weather will remain infectious longer.
- They saw very little difference under levels of humidity on surfaces, however the scientists stress that humidity likely does matter when the particles are in the air by affecting how fast the aerosols dry out. The research team is continuing to study the molecular details of virus-like particle degradation.
- “When it comes to fighting the spread of this virus, you kind of have to fight every particle individually. And so you need to understand what makes each individual particle degrade,” Vershinin said. “People are also working on vaccines and are trying to understand how the virus is recognized? All of these questions are single particle questions. And if you understand that, then that enables you to fight a hoard of them.”
G. The Road Back?
1. Antibodies as C19 insurance
- The U.S. can buy a Covid insurance policy for next year. The federal government should scale up production of antibody drugs to make as many doses as possible. The Food and Drug Administration has cleared two such drugs, from Regeneron and Eli Lilly, for emergency use. For newly diagnosed patients, they reduce the risk of severe disease.
- Making them is relatively straightforward, but supply is limited because the government didn’t find enough manufacturing space in the spring. Regeneron and Lilly took extraordinary steps to increase their own production. They knew they had to make these drugs in the U.S., lest other nations try to nationalize production and pocket the medicines. Each company freed up much of its domestic manufacturing capacity by shifting production of other drugs to places like Europe. Each company also joined forces with another large manufacturer to secure additional production capacity— Amgen teamed up with Eli Lilly, and Roche worked with Regeneron. The federal government relaxed certain rules to enable these collaborations. This will produce a combined supply of six million to seven million doses next year.
- But that isn’t enough. Most biotech companies prepare for disruptions in manufacturing by freezing and stockpiling enough of their most profitable drugs to last about two years. Why not pay these plants to use their capacity for antibody production? Companies can dip into reserves to avoid creating a shortage of other important medicines.
- A manufacturer can’t flip to making antibodies overnight. It’d take about six months to convert a facility to the Covid drug and another six months to return it to its original purpose. But a big facility that makes the Covid antibodies at full throttle for about eight months could rack up some 2.5 million doses.
- The government can help backstop the risks to any manufacturer willing to become a contract manufacturer for the Covid medication. The government can agree to buy the antibody and stockpile it at a price that makes it worthwhile. Regeneron and Lilly would be paid to license their drugs for such an arrangement.
- The government can freeze some of the active pharmaceutical ingredient and store it away as a hedge against another tough Covid winter next year. The raw ingredient can stay frozen for at least three years. And making the active ingredient is the hard part. Thawing it and turning it into finished drug would take less than a month.
- I’ve written about the antibody drugs several times on these pages. They were always the best bet for reducing the death and suffering from Covid this fall. Yet supply is severely constrained, and the two available drugs must be rationed, somewhat arbitrarily, because the government didn’t do everything possible last spring to ramp up manufacturing.
- There is still an opportunity to invest in making more antibodies. Not everyone will be able to get vaccinated, and some will choose not to. There will be many patients who need these medicines.
2. At Least 25% of World May Not Have Access to a C19 Vaccine Until 2022
- Nearly a quarter of the world’s population may not have access to a C19 vaccine until at least 2022, warns a study published by The BMJ today.
- A second study estimates that 3.7 billion adults worldwide are willing to have a C19 vaccine, highlighting the importance of designing fair and equitable strategies to ensure that supply can meet demand, especially in low and middle income countries.
- Taken together, these findings suggest that the operational challenges of the global C19 vaccination program will be at least as difficult as the scientific challenges associated with their development.
- In the first study, researchers from the Johns Hopkins Bloomberg School of Public Health analyzed pre-orders for C19 vaccines ahead of their regulatory approval that had been publicly announced by countries around the world.
- By November 15, 2020, several countries had reserved a total of 7.48 billion doses, or 3.76 billion courses from 13 manufacturers, out of 48 C19 vaccine candidates in clinical trials.
- Just over half (51%) of these doses will go to high income countries, which represent 14% of the world’s population, say the authors. Low and middle income countries will potentially have the remainder, despite these countries comprising more than 85% of the world’s population.
- If all of these vaccine candidates were successfully scaled, the total projected manufacturing capacity would be 5.96 billion courses by the end of 2021, with prices ranging from $6.00 (£4.50; €4.90) per course to as high as $74 per course.
- Up to 40% of the vaccine courses from these vaccine manufacturers might potentially remain for low- and middle-income countries. However, this will depend, in part, on how high-income countries share what they procure and whether the US and Russia participate in globally coordinated efforts.
- But the authors point out that even if all of these vaccine manufacturers were to succeed in reaching their maximum production capacity, at least a fifth of the world’s population would not have access to vaccines until 2022.
- “This study provides an overview of how high-income countries have secured future supplies of C19 vaccines, but that access for the rest of the world is uncertain,” they write. “Governments and manufacturers might provide much-needed assurances for equitable allocation of C19 vaccines through greater transparency and accountability over these arrangements.”
- In the second study, researchers based in China and the US estimated target populations for whom vaccines would be required, to help guide development of fair and equitable allocation strategies across the globe.
- They find that target population sizes for C19 vaccination vary widely by geographical region, vaccine objectives (such as maintaining essential core services, reducing severe C19, and stopping virus transmission), and the impact of vaccine hesitancy in reducing demand.
- They point to evidence suggesting that around 68% of the global population (3.7 billion adults) is willing to receive a C19 vaccine, and say their findings “provide an evidence base for global, regional, and national vaccine prioritization and allocation.”
- “Variations in the size of the target populations within and between regions emphasize the tenuous balance between vaccine demand and supply, especially in low and middle income countries without sufficient capacity to meet domestic demand for C19 vaccine” they conclude.
- Both studies are observational, and the authors acknowledge the implications of uncertainty and incomplete information for their analyses.
- Nevertheless, these findings illustrate the considerable scale and complexity of manufacturing, purchasing, distributing, and administering C19 vaccines in a way that meets global needs, and does so equitably among nations and populations.
- In a linked editorial, Jason Schwartz at Yale School of Public Health points out that many countries have already shown a commitment to equitable global access to C19 vaccines by purchasing through the COVAX Facility — an initiative that invests part of the payment in vaccines for poorer countries.
- But he says vigilance is required “to ensure that such aspirations are realized in the months and years ahead.”
- He argues that the successful, equitable implementation of C19 vaccination programs “requires unprecedented global coordination and a sustained commitment of resources — financial, logistical, and technical — from high-income countries.”
- In particular, he says US participation in vaccination efforts “will be invaluable in ensuring that all populations globally have access to the C19 vaccines that will ultimately help bring an end to this devastating global health crisis.”
H. Back to School!?
1. When Will C19 Vaccines Be Available for Kids?
- When will C19 vaccines be available for children, and will they be safe?
- Parents are asking those questions as the first Covid vaccine authorized for adults and older teens begins to roll out across the country. But the timeline for children is still unclear. Here’s what parents need to know.
Why isn’t a vaccine available for children yet?
- Researchers have yet to begin clinical trials in children under 12; trials in teens have just recently started. It’s not unusual in drug development to test adults first: New drugs and vaccines are often tested on adults before children, whose bodies are still developing and can have different responses to medication. In the case of Covid, adults are also generally more at risk for severe complications. Covid vaccines for younger children especially may require different dosage levels or formulations than the adult versions. Kids generally can’t get the vaccine until it is authorized for their specific age.
- The result is a delay in children having access to the vaccine, creating uncertainty over whether kids will be vaccinated before the start of the 2021 school year.
Why is it important for children to be vaccinated?
- A delay in vaccinating children could slow down the country’s ability to reach herd immunity, the point at which enough people are immune to a disease to make its spread unlikely. Studies estimate about 75% to 80% of the U.S. population needs to be immune to C19 to reach herd immunity.
- “It would be very, very difficult for us to reach herd immunity before vaccines are available to younger individuals,” says Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health.
- In general, children don’t get as seriously sick from the new coronavirus at the same rates as adults do, notes Roberta DeBiasi, division chief of Infectious Diseases at Children’s National Hospital in Washington, D.C. But cases in children are rising, with more than 1.4 million U.S. children infected so far, according to the most recent estimates from the American Academy of Pediatrics and Children’s Hospital Association. “They clearly are spreading the virus to vulnerable adults, grandparents and health care workers, so it’s really important that children are vaccinated,” says Dr. DeBiasi.
- And children themselves have become seriously ill or died from the virus. Children need to be vaccinated to prevent hospitalizations and rare but serious complications such as myocarditis or multisystem inflammatory syndrome (MIS-C), a hyperinflammatory response to the new coronavirus.
- “I have still seen really sick kids come into our hospital,” says Grace Lee, a professor of pediatrics at Stanford University School of Medicine.
How does a delay in vaccinating kids affect the need to continue taking Covid precautions?
- Until herd immunity is reached, measures like social distancing and masking will need to remain in place, even for those who have been vaccinated, experts say. That includes in schools. “We’re still in a long haul with schools,” says Dr. Mina.
Does Covid severity vary depending on kids’ age?
- Rates of infection, transmission and serious illness from C19 appear to increase as children get older, research has shown. “I think it was a mistake not to move more quickly on adolescents,” says Andrew T. Pavia, chief of pediatric infectious diseases at the University of Utah. “They get sick with the virus more so than younger kids and are important in transmission.”
Are companies starting to test vaccines in children?
- Pfizer and its German partner BioNTech started testing their vaccine candidate in children 12 and older this fall. A Pfizer spokeswoman said they expect full safety and efficacy results for adolescents ages 12 to 17 in early 2021. They are working with regulators on a pediatric study plan for younger age groups which will potentially require a modified formulation or dosing schedule, she said.
- Moderna, working in partnership with the National Institute of Allergy and Infectious Diseases, is finalizing a design for a trial in children under 12, which they anticipate launching in the first quarter of the year. A spokeswoman said they hope to have a vaccine for adolescents by the start of the 2021 school year.
What needs to happen before a vaccine for children will be authorized?
- The timetable on producing vaccines for children and adolescents will depend on the type of studies done.
- Experts say efficacy studies in children don’t necessarily need to be done. Rather, when vaccines exist for adults, companies often do studies demonstrating safety in children and what are called “bridging” studies demonstrating that the immune response in children is similar to adults. But a spokeswoman for Pfizer said their studies in adolescents and children are not bridging studies.The adolescents are part of the current Phase 3 study; a planned under-12 study would involve a different formulation and dose so will require a new safety and efficacy study.
- Stanford’s Dr. Lee, a member of the CDC’s Advisory Committee on Immunization Practices, which makes recommendations on vaccines once they’re authorized for use, says she wants to see both safety and some efficacy data on the vaccine in children.
Are side effects a concern in children?
- Despite the fact that the vaccine has been tested in tens of thousands of people, unexpected side effects can still surface.
- On the first day that the U.K. started vaccinations, two people suffered allergic reactions. That prompted the U.K.’s health regulatory agency to advise those with a history of significant allergic reactions to vaccines, medicine or food to hold off on receiving the inoculation for now.
- Some doctors say there is a possibility, particularly with the novel type of vaccines produced by Pfizer and Moderna using messenger RNA, that side effects such as fever, fatigue and headaches seen in adults may be more pronounced in children. Dr. Pavia says mRNA vaccines trigger side effects in part through the innate immune system, which is more robust in younger children.
- Studies need to be done in children so physicians can educate parents and children about what to expect in terms of side effects, particularly because the vaccine will likely require boosters and they don’t want families to be scared off by strong reactions. Side effects are a sign that the vaccine is working and the immune system is doing its job, doctors say. Even if the side effects are similar to C19 the vaccine can’t cause C19 and those side effects shouldn’t pose the same potential serious health effects as the coronavirus.
- Cody Meissner, a professor of pediatrics at Tufts Children’s Hospital and a member of the federal advisory board that makes recommendations to the U.S. Food and Drug Administration, says it’s important to evaluate the potential for unanticipated reactions in children, including MIS-C, which is believed to be triggered by the spike protein on the new coronavirus. He acknowledges this reaction is unlikely as the amount of protein produced by the vaccine is much smaller than in the virus from a natural infection.
- While he strongly agrees that a vaccine is needed for children, he would first like to wait and see how vaccination goes with the millions of adults about to get it, reasoning that the lower risk of severe disease in children changes the risk-benefit calculation. “If by early 2021 we don’t see any surprises, then that’s a firm basis by which to look at adolescents and young children,” he says.
I. Innovation & Technology
1. Detecting C19 in Less Than 5 Minutes With a Paper-Based Electrochemical Sensor
- As the C19 pandemic continues to spread across the world, testing remains a key strategy for tracking and containing the virus. Bioengineering graduate student, Maha Alafeef, has co-developed a rapid, ultrasensitive test using a paper-based electrochemical sensor that can detect the presence of the virus in less than five minutes. The team led by professor Dipanjan Pan reported their findings in ACS Nano.
- “Currently, we are experiencing a once-in-a-century life-changing event,” said Alafeef. “We are responding to this global need from a holistic approach by developing multidisciplinary tools for early detection and diagnosis and treatment for the coronavirus (SARS-CoV-2).”
- There are two broad categories of C19 tests on the market. The first category uses reverse transcriptase real-time polymerase chain reaction (RT-PCR) and nucleic acid hybridization strategies to identify viral RNA. Current FDA-approved diagnostic tests use this technique. Some drawbacks include the amount of time it takes to complete the test, the need for specialized personnel and the availability of equipment and reagents.
- The second category of tests focuses on the detection of antibodies. However, there could be a delay of a few days to a few weeks after a person has been exposed to the virus for them to produce detectable antibodies.
- In recent years, researchers have had some success with creating point-of-care biosensors using 2D nanomaterials such as graphene to detect diseases. The main advantages of graphene-based biosensors are their sensitivity, low cost of production and rapid detection turnaround. “The discovery of graphene opened up a new era of sensor development due to its properties. Graphene exhibits unique mechanical and electrochemical properties that make it ideal for the development of sensitive electrochemical sensors,” said Alafeef. The team created a graphene-based electrochemical biosensor with an electrical read-out setup to selectively detect the presence of SARS-CoV-2 genetic material.
- There are two components to this biosensor: a platform to measure an electrical read-out and probes to detect the presence of viral RNA. To create the platform, researchers first coated filter paper with a layer of graphene nanoplatelets to create a conductive film. Then, they placed a gold electrode with a predefined design on top of the graphene as a contact pad for electrical readout. Both gold and graphene have high sensitivity and conductivity which makes this platform ultrasensitive to detect changes in electrical signals.
- Current RNA-based C19 tests screen for the presence of the N-gene (nucleocapsid phosphoprotein) on the SARS-CoV-2 virus. In this research, the team designed antisense oligonucleotide (ASOs) probes to target two regions of the N-gene. Targeting two regions ensures the reliability of the senor in case one region undergoes gene mutation. Furthermore, gold nanoparticles (AuNP) are capped with these single-stranded nucleic acids (ssDNA), which represents an ultra-sensitive sensing probe for the SARS-CoV-2 RNA.
- The researchers previously showed the sensitivity of the developed sensing probes in their earlier work published in ACS Nano. The hybridization of the viral RNA with these probes causes a change in the sensor electrical response. The AuNP caps accelerate the electron transfer and when broadcasted over the sensing platform, results in an increase in the output signal and indicates the presence of the virus.
- The team tested the performance of this sensor by using C19 positive and negative samples. The sensor showed a significant increase in the voltage of positive samples compared to the negative ones and confirmed the presence of viral genetic material in less than five minutes. Furthermore, the sensor was able to differentiate viral RNA loads in these samples. Viral load is an important quantitative indicator of the progress of infection and a challenge to measure using existing diagnostic methods.
- This platform has far-reaching applications due to its portability and low cost. The sensor, when integrated with microcontrollers and LED screens or with a smartphone via Bluetooth or wifi, could be used at the point-of-care in a doctor’s office or even at home. Beyond C19, the research team also foresees the system to be adaptable for the detection of many different diseases.
- “The unlimited potential of bioengineering has always sparked my utmost interest with its innovative translational applications,” Alafeef said. “I am happy to see my research project has an impact on solving a real-world problem.”
2. Your Old Radiator Is a Pandemic-Fighting Weapon
- Turn-of-the-century faith in ventilation to combat disease pushed engineers to design steam heating systems that still overheat apartments today.
- Age and inexpert maintenance have given century-old radiators a bad reputation. But when first installed, steam heating systems represented a powerful tool to fight infectious disease.
- The coronavirus pandemic has revived interest in the role design has played fighting infectious diseases. Most famously, the trailblazing modern architecture of the early 20th century — open to nature and filled with light and air, as practiced by designers such as Alvar Aalto and Richard Neutra — reflected au courant ideas about health and wellness, especially in combating the scourge of tuberculosis (which also influenced bathroom design).
- The battle against pathogens reshaped the inner working of buildings, too. Take that familiar annoyance for New Yorkers: the clanky radiator that overheats apartments even on the coldest days of the year. It turns out that the prodigious output of steam-heated buildings is the direct result of theories of infection control that were enlisted in the battle against the great global pandemic of 1918 and 1919.
- The Spanish Influenza, which caused just over 20,000 deaths in New York City alone, “changed heating once and for all.” That’s according to Dan Holohan, a retired writer, consultant, and researcher with extensive knowledge of heating systems and steam heating. (Among his many tomes on the topic: The Lost Art of Steam Heating, from 1992.) Most radiator systems appeared in major American cities like New York City in the first third of the 20th century. This golden age of steam heat didn’t merely coincide with that pandemic: Beliefs about how to fight airborne illness influenced the design of heating systems, and created a persistent pain point for those who’ve cohabitated with a cranky old radiator.
- Health officials thought (correctly) that fresh air would ward off airborne diseases; then as now, cities rushed to move activities outdoors, from schools to courtrooms. When winter came, the need for fresh air didn’t abate. According to Holohan’s research, the Board of Health in New York City ordered that windows should remain open to provide ventilation, even in cold weather. In response, engineers began devising heating systems with this extreme use case in mind. Steam heating and radiators were designed to heat buildings on the coldest day of the year with all the windows open. Anybody who’s thrown their windows open in January, when their apartment is stifling, is, in an odd way, replicating what engineers hoped would happen a century ago.
- The memories of the flu pandemic lingered. Engineering books from the 1920s often mentioned this need to design heating systems, notably the boilers and radiators, to operate with all windows open, a requirement of the “fresh air movement,” Holohan says. This health crusade, which has its roots in the post-Civil War era, saw fresh air as a necessity for good health; adherents believed that rooms with closed windows and tight airflow meant that others would breathe in your vapors and catch disease. The theory originated before modern germ theory, at a time when tuberculosis was a significant health threat. “They called unventilated air the ‘national poison,’” Holohan says.
- A key proponent of the idea was Lewis Leeds, a health inspector for Union Army field hospitals who came to the conclusion that “vitiated,” or spoiled, air was the cause of the many diseases. The “spent breath” of the occupants of poorly ventilated homes contributed to 40% of the deaths in the country, he claimed, and often said “man’s own breath is his greatest enemy.” He would spend decades promoting the cause, designing ventilation schemes for buildings, penning a 1869 book, Leeds on Ventilation, and lecturing across the country. He explained his ideas with the aid of a “magic lantern” projector — think old-timey Powerpoint presentations. He’d show slides of a family in their drawing room, then add a slide showing red air coming out of the father’s mouth. The child crawling on the floor would eventually fall over. It “scared people to death,” Holohan says.
- Leeds was joined in his fervent ventilation campaign by author Harriet Beecher Stowe, of Uncle Tom’s Cabin fame. With her sister, Catherine, Stowe would coauthor a 1869 book, The American Woman’s Home, that claimed “tight sleeping-rooms, and close, air-tight stoves, are now starving and poisoning more than one half of this nation.” It also introduced terrifying scenarios to shock American readers into action, such as this passage about the impact of vitiated air on a child:
- Little Jim, who, fresh from his afternoon’s ramble in the fields, last evening said his prayers dutifully, and lay down to sleep in a most Christian frame, this morning sits up in bed with his hair bristling with crossness, strikes at his nurse, and declares he won’t say his prayers—that he don’t want to be good. The simple difference is, that the child, having slept in a close box of a room, his brain all night fed by poison, is in a mild state of moral insanity.
- These ideas would become more formally accepted by architects and engineers during the beginning years of the 20th century. The 1901 New York State Tenement House Act mandated that every room have an outdoor facing window. New York City Health Commissioner Royal Copeland, who, as a U.S. senator in the 1920s proposed redesigning the Senate Chamber to deal with deadly, stale air, would praise the tenement laws as having a significant impact during the flu pandemic.
- By the time the Spanish Flu hit, the maxims of the fresh air movement had become popular enough to impact building designs. The toll of the pandemic solidified this thinking, says Holohan. Having robust steam boilers that could keep apartments and dwellings comfortable with open windows became standard in New York City, as well as other northern cities in cold climates, such as Detroit, Chicago, Denver, Boston and Philadelphia.
- In the early 20th century, steam heat represented a big step up from coal stoves and fireplaces.
- The pandemic abated in 1920 but these standards had become locked into place. The architecture firm KPF found that nearly 75% of Manhattan’s existing square footage was built between 1900 and 1930. And since steam heat systems are incredibly durable, they’ve lasted for generations.
- In the ensuing decades, shifts in building practice and fuel usage made the problem of over-indexed steam heat worse. The type of fuel used to heat the steam boilers changed, from coal to heating oil to natural gas, and during the changeover, Holohan says, they didn’t properly resize boilers or systematically change design standards to account for the changing power source; replacement boilers were kept big to err on the side of caution. Better windows, especially double-pane varieties, would provide the benefit of better insulation and less heat loss, but only served to lock in the impact of overly aggressive radiators. (If you own an old radiator-equipped house, you might have noticed how overpoweringly effective they can be after you replace leaky older windows with more well-insulated modern replacements.)
- By the 1930s, Holohan says, a few common remedies to mitigate excessive radiator heat came into practice that last to this day. Researchers at the National Bureau of Standards found that if radiators were painted with a special kind of bronzing paint — specifically, the silver tone found in many radiators today — it would reduce some of the heat transfer. Same goes with “radiator cozies,” knitted covers sometimes placed over the ribs of radiator pipes. They have the added benefit of protecting kids from getting burned, but one reason they became commonplace was as a way to blunt excess heat.
- Roughly 80% of residential buildings in NYC are still heated by steam, and surveys with tenants found that 70 % are chronically overheated in winter, according to Demystifying Steam, a 2019 report by the Urban Green Council. The durability of steam “has locked into place technical limitations of a century ago, ” the report noted; their role as disease-fighters forgotten, radiators are now seen as energy-sucking dinosaurs. “Many tenants open windows for relief, even on the coldest days,” the report found, “but steam systems are so unbalanced that other residents in these same buildings don’t receive enough heat.”
- Steam’s grip on the city’s building stock has made the challenge of meeting environmental goals much harder, in effect overheating more than merely the buildings in which they operate. According to John Mandyck, CEO of the Urban Green Council, 70% of the climate emissions in New York City are generated by buildings, with the biggest share from the fossil fuels used for heat and hot water in large, multifamily buildings.
- Steam might get a bad rap now, but Holohan notes that its inefficiencies can be traced to poor maintenance and long out-of-date building codes. (It’s not supposed to clank either.) “The banging and clanging wasn’t normal,” he says. “Steam heat was fast and silent when it was first installed. When it’s properly tended, it can be an efficient way to heat. Most people just don’t know how to do it right.”
- As a Covid-haunted winter looms, residents of steam-heated buildings may get another opportunity to crank their radiators up and put them to their intended use. Holohan says he’s bemused to see his field of expertise reemerge in connection with the current pandemic, as ventilation is being again promoted as a key strategy to cut infection.
- “I’ve been talking about this for like 30 years or more,” he says. “And suddenly I’m living it.”
1. New Research Shows Every Week of C19 Lockdown Increases Harmful Binge Drinking
- Harmful drinking among adults increases the longer they spend at home in lockdown, according to a study published in the peer-reviewed American Journal of Drug and Alcohol Abuse.
- The research, based on a survey of nearly 2,000 over-18s in the US, is the first to highlight the relationship nationally between hazardous drinking and life stresses triggered by the C19 pandemic and the associated “lockdowns.”
- The findings show the odds of heavy alcohol consumption among binge drinkers — those who, within two hours, consumed five or more drinks for men and four and above for women — rose an extra 19% for every week of lockdown.
- The odds of increased alcohol intake overall for binge drinkers was more than double that of people who did not drink excessively (60% vs 28%), especially those with depression or a history of the disease.
- Carried out by experts at the University of Texas Health Science Center School of Public Health, in Dallas, the study also highlights that:
- During the pandemic, binge drinkers on average drank four drinks per occasion, compared to two drinks among non-binge drinkers.
- Participants who drank at harmful levels during the pandemic would consume seven drinks maximum on one occasion. This is compared to a maximum of two per session during the pandemic for those who did not.
- Living with children in lockdown minimally reduced the odds (by 26%) of turning to the bottle for people in general.
- The researchers are now calling for new intervention and prevention strategies for people in isolation at risk of hazardous drinking. Otherwise, they say there could be long-lasting health consequences.
- “Increased time spent at home is a life stressor that impacts drinking and the C19 pandemic may have exacerbated this stress,” says Sitara Weerakoon, a PhD candidate from the University of Texas.
- “Future research should consider the potential for depressive symptoms acting as a moderator (a factor that changes the impact) in the relation between the time spent under a shelter-in-place mandate (lockdown) and binge drinking.
- “Additional research is (also) needed to develop best treatment for people with substance use disorders who may be more susceptible to adverse health outcomes.”
- The study aim was to identify a link between C19-related stress factors and changes in alcohol consumption and binge drinking since the pandemic began.
- The data was from an online survey completed by 1,982 adults from mid-March to mid-April, which coincided with the first US state-wide stay-at-home order on March 19. The average age of participants was 42 and the majority were white (89%) and female (69%).
- The majority (70%) of participants were relatively high earners, a factor already associated with hazardous alcohol use. The authors say future research is needed in a more “generalizable population.”
K. Practical Tips & Other Useful Information
1. Your home is a hotspot for C19
- A new analysis that looked at 54 studies in over 20 countries found homes where someone was sick with C19 continued to be hotspots for virus transmission, even if overall community spread was down.
- “This is yet another study that reminds us of how contagious the virus that causes C19 is, and how hard it is to keep from infecting others if one lives in crowded, multigenerational housing,” said CNN Medical Analyst Dr. Leana Wen, an emergency physician and visiting professor at George Washington University Milken Institute School of Public Health, who was not involved in the study.
- Spouses were at higher risk than other family members, likely due to sleeping in the same room, intimacy and prolonged contact, according to the study published Monday in the journal JAMA Network Open.
- Risk was higher if the family member showed symptoms of C19 — such as cough, sneezing, body aches, chills and fever — than if the person showed few or no signs of the virus, the study found. Risk was also higher between adults than between adults and children.
Quickly moving infection
- A recent study by the US Centers for Disease Control and Prevention found infection among household members occurred quickly. Over half of the people (53%) who lived with someone battling C19 became infected within a week, researchers found. Some 75% of these secondary infections occurred within five days of the first symptoms in the initial patient.
- Fewer than half of infected household members had symptoms at the time infection was first detected.
- “Many reported no symptoms throughout 7 days of follow-up, underscoring the potential for transmission from asymptomatic secondary contacts and the importance of quarantine,” the CDC team reported.
Isolate yourself or your loved one
- Staying isolated from other household members is challenging, especially if you are in a small space or there are children in the home.
- “If you have somebody at home who’s older or immunocompromised, you may want to isolate them to one side of the house so the kids and everybody else aren’t around them on a regular basis,” said pediatrician Dr. Tanya Altmann, editor in chief of the American Academy of Pediatrics’ book “Caring for Your Baby and Young Child: Birth to Age 5 and The Wonder Years,” in a prior interview.
- “If it’s a child that you have to care for, then you may have to make the decision to isolate one adult with the child,” she added. “That adult would be caring for the child and the other adult would be responsible for the rest of the family.”
- And of course, all of this will be extremely difficult for a single parent “who might be the only one,” said pediatrician Dr. Jenny Radesky, a spokesperson for the American Academy of Pediatrics, in a prior interview.
- “Know who your neighbors are, even what your neighborhood social network might be,” said Radesky, an assistant professor of pediatrics at the University of Michigan. “You may not be that close interpersonally, but someone may be willing to do a grocery store drop-off or pick-up medications, because we’re all in this together.”
- The rest of the family should practice isolation as well, Radesky added.
- “Unfortunately you need to keep the whole household under isolation,” she said. “The patterns of C19 spread suggest that clusters of people who live close together are at highest risk of getting it from one another. If children are part of that household, they may show minimal symptoms but still be contagious.”
- Consider having everyone living in home wear a mask inside. Doing so was 79% effective at preventing the spread of the virus, according to a recent study, when family members started wearing masks before symptoms emerged in the first person infected.
- If you live alone, your challenge is to monitor your symptoms and care for yourself when you’re not feeling well. Be sure to have a plan in place to get food and medications delivered to your home, and find someone who can be responsible for virtually checking in on you on a regular basis.
- Stock or ask loved ones to provide the room with all relevant forms of entertainment: TV, computer, iPad, books, even games that you could play via FaceTime or Skype.
A supply checklist
- Don’t hesitate to order online or ask loved ones to provide basic supplies, which include:
- A working thermometer to monitor fever, which is considered to be 100 degrees Fahrenheit (37.7 degrees Celsius), and a method to clean it, such as isopropyl alcohol
- Fever-reducing medications, such as acetaminophen
- A box of rubber or latex disposable gloves and face masks
- A 60- or 90-day supply of other necessary prescription medicines
- Regular soap and 70% alcohol-based hand sanitizer (antibacterial soap isn’t necessary if you wash properly, and that way you won’t contribute to the world’s growing antibiotic-resistant superbugs)
- Tissues to cover sneezes and coughs. But there is really no need to hoard toilet paper — this is a respiratory disease
- Regular cleaning supplies, kitchen cleaning gloves and trash can liners
- Disinfectant cleaning supplies — the CDC suggests picking from a list that meets the virus-fighting standards of the US Environmental Protection Agency, but says you can also make your own version by using 1/3 cup unexpired bleach per gallon of water or 4 teaspoons bleach per quart of water. Never mix bleach with ammonia or any other cleanser because it produces toxic gases
Cover up and disinfect
- Everyone in the home should keep a face mask on, unless you or your loved one is having “trouble breathing” or is “unconscious, incapacitated, or otherwise unable to remove the mask without assistance,” the CDC says.
- Maximize isolation and protective actions, Altmann stressed.
- “You can have a healthy person leave the sick one food and drinks at the door, and then go wash their hands,” Altmann explained. “Wear gloves to pick up the empty plates, take them back to the kitchen and wash them in hot water with soap, or preferably with a dishwasher, and wash your hands again.”
- Do not share drinking glasses, cups, forks or other eating utensils or dishes, the CDC says. Don’t share towels or bedding with other people in your home. When doing laundry, don’t shake the sick person’s dirty clothes to “minimize the possibility of dispersing virus through the air.”
- And caregivers should wear disposable gloves when handling that dirty laundry, the CDC says, throwing them away after each use.
- “If using reusable gloves, those gloves should be dedicated for cleaning and disinfection of surfaces for C19 and should not be used for other household purposes. Clean hands immediately after gloves are removed,” the CDC advises.
What happens if there is only one bathroom in the home?
- “If everyone has to use to use the same bathroom, try to leave at least two hours after the person in isolation has used it before someone else goes,” Wen advised.
- Dedicate a lined trash can for any tissues or other paper or disposable products used by a sick person, the CDC says, adding that caregivers should “use gloves when removing garbage bags, handling and disposing of trash. Wash hands after handling or disposing of trash.”
- And remember: Call 911 immediately if you or your loved ones have any of these symptoms: increased or sudden difficulty breathing or shortness of breath; a persistent pain or pressure in the chest; and any sign of oxygen deprivation, such as new confusion, bluish lips or face, or you can’t arouse the sick person.
Keeping everyone else from getting sick
- To be clear: After a positive C19 diagnosis, everyone in the house needs to isolate themselves from the outside world as much as possible.
- “I would recommend that families find friends who can drop off essential groceries or medications, not go to work, and not play with other children — even outside,” Radesky said.
- “If you don’t have friends who can drop off groceries or essential items, see if the local stores can deliver the items for you. I’m sure they would appreciate not having a potential C19 exposure in their store,” she added.
- If a family member without symptoms believes it is absolutely essential to go outside to the grocery store, pharmacy or to check on a family member, be aware that you may well be contagious and anything you touch could transfer the virus — even without symptoms.
- “I would urge people not to do this,” Radesky said. “The way we will beat this virus is by reducing the number of times that each infected person transmits the virus to another person. So the more you can do to stop the virus in its tracks — in other words, your family doesn’t give it to anyone else, and you don’t bring it to your workplace or a local store — the sooner we will be done with this!”
- To reduce virus transfer inside your home, try to keep an air flow in the rest of the home with opened windows or doors with screens, if weather permits. The CDC says “improving ventilation helps remove respiratory droplets from the air,”
- “I’d keep windows open in all shared spaces,” advised Wen. “Also, an air purifier with a HEPA filter could help. So would a humidifier, as viruses linger longer in dry air — especially in the shared space.”
- Have everyone wash their hands at every opportunity. Clean and disinfect all those commonly shared surfaces — don’t forget the refrigerator and microwave handles!
- Keep everyone as stress-free as possible — a hard task for sure — and focus on healthy eating, regular exercise and quality sleep.
- Even though there is no indication that pets can give or get C19, the CDC suggests keeping pets away from sick people.
- “Since animals can spread other diseases to people, it’s always a good idea to practice healthy habits around pets and other animals,” the CDC says. “If you must care for your pet or be around animals while you are sick, wash your hands before and after you interact with pets.”
When is your home isolation over?
- If you tested positive but had no symptoms, you can stop isolating at home 10 days after the date you had your positive test, the CDC says.
- For those with symptoms, the CDC says you can be around others when:
- It’s been 10 days or more since symptoms first appeared
- AND you’ve gone 24 hours with no fever without the use of fever-reducing medications
- AND other symptoms of C19 are improving
- “A limited number of persons with severe illness may produce replication-competent virus beyond 10 days that may warrant extending duration of isolation and precautions for up to 20 days after symptom onset,” the CDC says. Consider consultation with infection control experts, the agency says.
- A loss of taste and smell can remain for weeks or even months after recovery, the CDC notes, but that does not mean you need to remain isolated.
- However, if you have a severely weakened immune system or were more severely sick with C19 — such as being admitted to a hospital and needing oxygen — the rules change, according to the CDC:
- “Your healthcare provider may recommend that you stay in isolation for longer than 10 days after your symptoms first appeared (possibly up to 20 days),” the CDC says.
- “Persons who are severely immunocompromised may require testing to determine when they can be around others. Talk to your healthcare provider for more information.”
- These are scary times, but hopefully these tips will help ease your anxiety and prepare you and your family for the worst, while hoping and striving for the best.
2. Which C19 Rules Are Useless? Too Many of Them
- A clutter of unhelpful pandemic rules is wearing people down. One-way systems in stores, outdoor mask mandates, ceaselessly cleaning groceries and packages — should these things be our top priorities for limiting the spread of C19?
- Harvard’s Joseph Allen is an associate professor of exposure assessment science and one of the world’s experts on why some indoor spaces are worse than others for spreading viruses. Like other experts, he agrees that poorly ventilated indoor sites are the prime spreading ground for the coronavirus (SARS-CoV-2). So the longer people spend in any indoor space with other people, the greater the risk they pose to themselves and others.
- I asked him: Wouldn’t it be better if we did away with the one-way system so that people could dispatch with their grocery shopping quickly, without having to endure long waits behind price-comparers or other slowpokes? The answer is yes. Eliminating those annoying arrows would probably make shopping safer as well as less stressful.
- Businesses are, of course, free to impose their own rules, but it’s unlikely many would knowingly make shopping less safe. The fault lies with the public health community for being too shy in talking about which rules don’t help, leaving us with a tangle of rules and recommendations — and pandemic fatigue.
- State rules have an even bigger effect on our lives and are often thrown at people with no transparency. My state of Rhode Island has recently become one of the worst five states for per-capita infections, despite getting praise from Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, at the end of the summer for our strict rules and good compliance. With cases already climbing in late November, Governor Gina Raimondo held a press conference where she scolded citizens for not following the rules.
- Soon afterwards, a talk radio host voiced what I was thinking. Who are these people filling up the hospitals? Where do they live? What kind of work do they do? Do we have any idea how they got the virus? And which rules, exactly, were they breaking?
- As risk communication consultant Peter Sandman has said early in the pandemic, a public health policy that people don’t follow is a failed policy. That means even a really solid, science-based set of rules can fail if it’s not communicated with a clear rationale.
- In Massachusetts, governor Charlie Baker has focused his latest round of rules on outdoor mask wearing — something that many experts have said is unlikely to help since the virus is extremely unlikely to be transmitted over distances outside. The British Scientific Advisory Group for Emergencies has deemed outdoor mask wearing of negligible benefit.
- Baker’s ruling prompted Harvard epidemiologist Julia Marcus to suggest in Boston.com that he’s playing pandemic theater. “Arbitrary public health rules are a way to break the public’s trust, which is essential to keeping people engaged in public health efforts,” she told a reporter for the site. “I think a mandate like this — that people know is arbitrary — is going to do more to reduce trust than it will to reduce infections.”
- Harvard’s William Hanage, who studies infectious disease dynamics, told me that people don’t need more rules. They need more information about how the virus is transmitted so they can take steps to avoid it. “When you phrase things in terms of rules, it leads people to try to come up with ways to get around those rules,” he says.
- Rules can become a form of misinformation. The rules in many states seem to suggest that walking outside is dangerous and eating in a restaurant is safe, but Hanage says the truth is the other way around.
- Baker has justified his outdoor mask mandate by saying it sends a message. The message I heard was that that the rules are not chosen for our health and welfare but to make our political leaders look like they are doing something.
- Rules should only be decreed along with evidence for their benefit, argued statistician and risk communication expert David Spiegelhalter in a piece for The Guardian: “Too often, the message is shaped by communication professionals working to ensure the greatest number of people ‘get the message’ rather than thinking about how to present the evidence so the greatest number of people can understand it, trust it, and then decide for themselves.”
- I hear from diverse readers who want to do the right thing, but need to know where to focus their efforts. A farmer in Florida recently wrote to me about the pandemic fatigue that’s affecting him and his neighbors. “What happens here is that we get worn out, beaten down and overloaded such that no matter how well-intentioned we are we are prone to latch onto something wrong.”
- “So I think people here get it that it’s serious … they like their neighbors and don’t want them dead,” he wrote. But they’re wondering how much effort to put into disinfecting groceries and kitchen counters — something that some media outlets recommended in the spring, as well as wearing gloves at the gas station, disinfecting credit cards and letting packages sit outside for a few days before opening them.
- Harvard disease expert Hanage says that the science to date points to the primary risk coming from what he calls the three C’s — close contact, closed spaces and crowds. He says in Japan, where they’ve had few C19 deaths, people are advised to avoid these — not just to wear masks in these situations but to limit them or avoid them altogether.
- One place where the informational clutter can get sorted out is the CDC. In an encouraging trend, the agency is starting to make recommendations by explaining why they’re likely to improve public health. The agency cited good reasons people should avoid traveling for the holidays, including many combinations of those three C’s. They’ve just issued new guidelines recommending masks when people are indoors outside their homes or cannot stay more than six feet away from other people. And they’ve just shortened the quarantine period for people exposed to the virus from 14 days to 10, or seven if you get a test at the end. Again, the rationale was explained — some cases can incubate for two full weeks, but most people develop symptoms sooner. A shorter quarantine period can still cut down on transmission and will get better compliance.
- It would be wonderful if the CDC could also start telling us which rules and recommendations are unlikely to work, so we can all concentrate on the ones that will. There’s some denial out there, but there’s also enormous curiosity and willingness to help. It’s a resource we can’t afford to keep squandering.
3. COVID Face Shields No Match for Sneeze Vortex Rings
- Do face shields provide enough protection to the wearers against C19 if they don’t also wear a mask? Spoiler alert: no. But researchers at Fukuoka University in Japan are working to create face shields safe enough to be worn alone.
- The researchers originally set out to explore whether surgical masks and face shields used as preventive measures are effective, as well as to determine if the stress of wearing a N95 surgical mask for long periods could be reduced.
- In Physics of Fluids, from AIP Publishing, Fujio Akagi and colleagues describe their work to gain a better understanding of what happens to the airflow around a face shield when someone nearby sneezes. Sneezes are intriguing, because they produce a fluid phenomenon known as vortex rings.
- “A vortex ring is a donut-shaped vortex that is generated by an instantaneous ejection of fluid from a circular orifice,” said Akagi. “This resembles bubble rings made by dolphins.”
- These vortex rings can capture microscopic particles, which sneezing also generates. What happens when a face shield wearer is exposed to a sneeze from an infected person standing 1 meter (39.3 inches) in front of them?
- “The vortex rings generated by the sneeze capture the microscopic droplets within the sneeze and transport them to the top and bottom edges of the face shield,” said Akagi, adding that droplets travel to the face shield wearer quickly — within 0.5 to 1 second after the start of the sneeze.
- “If this arrival time is synchronized with inhalation, the shield wearer will inhale the droplets,” Akagi said.
- The researchers made three findings everyone should know:
- First, droplets of sneezes are transported not only by the high velocity airflow caused by sneezing, but also by the vortex rings generated by sneezing.
- Second, microscopic droplets transported by these vortex rings can get inside the shield through its top and bottom edges.
- Third, face shields alone are not highly effective to prevent C19 infection.
- By gaining a better understanding of face shield weaknesses, researchers believe the protection can be enhanced by reducing the flow getting inside the shield.
- “We are currently developing and demonstrating several improved shields,” said Akagi. “We want to contribute to keeping people safe from infection, and believe that one day in the near future, medical workers will be able to prevent infection using only a face shield and a regular mask or, ideally, with only a face shield.”
L. Johns Hopkins COVID-19 Update
December 15, 2020
1. Cases & Trends
- Overview The WHO C19 Dashboard reports 71.35 million cases and 1.61 million deaths as of 4:00am EST on December 15. The global cumulative incidence surpassed 70 million cases on December 13. From the first reported C19 case, it took 90 days for the global total to reach 1 million cases.
- 1 case to 10 million- 177 days
- 10 to 20 million- 44 days
- 20 to 30 million- 37 days
- 30 to 40 million- 31 days
- 40 to 50 million- 21 days
- 50 to 60 million- 17 days
- 60 to 70 million- 17 days
- The WHO reported new records in terms of both weekly incidence and mortality. Weekly incidence was 3.4% higher than the previous week, the second consecutive week-to-week increase. Mortality increased for the eighth consecutive week, although only a moderate 0.8% increase over the previous week. Additionally, the WHO reported new daily records for both incidence and mortality on December 11, with 695,808 new cases and 13,033 deaths.
- The US CDC reported 16.11 million total cases and 298,266 deaths. The US reported a new single-day record for daily incidence on December 11, with more than 244,000 new cases. It continues to appear as though US daily incidence is beginning to taper off toward a peak or plateau; however, we have likely still not yet begun to see any effects from Thanksgiving travel and gatherings. If the Thanksgiving holiday had major impact on the US epidemic, we expect to begin to see the early evidence over the next week or two.
- In terms of mortality, the US is averaging 2,430 deaths per day, which corresponds to 1 US death every 36 seconds. To date, the US has only exceeded this rate for a 3-day period from April 19-21, at the very peak of the initial US surge and just days after New York City reported 3,700 previously unreported probable C19 deaths from the onset of its epidemic. We expect the US to surpass 300,000 cumulative deaths in this afternoon’s CDC update. From the first US death reported on February 29, it took 46 days to reach 25,000 deaths. From there:
- 25,000 to 50,000- 9 days
- 50,000 to 75,000- 13 days
- 75,000 to 100,000- 20 days
- 100,000 to 125,000- 31 days
- 125,000 to 150,000- 32 days
- 150,000 to 175,000- 24 days
- 175,000 to 200,000- 31 days
- 200,000 to 225,000- 34 days
- 225,000 to 250,000- 24 days
- 250,000 to 275,000- 14 days
- 275,000 to 300k- 11 days
- According to analysis published on the COVID Exit Strategy website, 34 states; Washington, DC; and Puerto Rico are reporting increasing C19 incidence over the past 2 weeks. Notably, the daily incidence has more than doubled in 3 states over that period—California, Maine, and South Carolina—and another 12 are reporting increases of 50% or more. Most of the increasing trends are in states along the East and West Coasts and the South, whereas states in the middle of the country are declining.
- In fact, a number of states that were severely affected earlier in the autumn resurgence have peaked in terms of daily incidence and are now reporting considerable decreases, including Iowa, Minnesota, Nebraska, North and South Dakota, Wisconsin, and Wyoming. These states were more severely affected earlier in the current surge, so it is not surprising that they are peaking earlier. Additionally, Hawai’i moved up from Caution Warranted to Trending Poorly as a result of worsening incidence and other indicators.
- According to analysis by the COVID Tracking Project, all but 3 states have reported record high daily incidence since the beginning of November, including 17 since last week. While the vast majority of states recently peaked or continue to report record-high and/or increasing incidence, regional differences are emerging here as well.
- The Midwest region is the only one to have passed a peak in daily incidence or hospitalizations, although mortality continues to increase across all 4 regions. The Midwest and South regions appear as though they may be at or approaching a peak in daily mortality, but more data are needed to better characterize the longer-term trends.
- Additionally, 13 states and Washington, DC, are reporting increasing hospitalizations over the past week, and another 13 are reporting positive trends but less than +10% cutoff to be classified as “Rising.” While the regional mortality may be beginning to turn in the Midwest, Iowa and North and South Dakota continue to report per capita daily mortality substantially higher than the rest of the country, on the order of 50% or higher than any other state.
- The Johns Hopkins CSSE dashboard reported 16.55 million US cases and 301,264 deaths as of 11:30am EST on December 15.
2. US FDA AUTHORIZES PFIZER VACCINE
- On December 11, the US FDA issued an Emergency Use Authorization (EUA) for the Pfizer/BioNTech vaccine, which allowed Pfizer to begin distributing the first allotments of the vaccine nationwide. The FDA also published guidance for vaccinators—including storage, thawing, dilution, and dosing information—and recipients.
- The EUA specifically authorizes the vaccine for use in individuals aged 16 years and older, but as we covered previously, not everyone in this population will be immediately eligible for vaccination. Eligibility will be expanded slowly, starting with priority populations such as high-risk individuals and essential workers. The only contraindication listed in the vaccine information is a history of allergies to vaccine ingredients, although safety monitoring and reporting will be ongoing as the vaccination program unfolds in order to identify any additional conditions associated that could be associated with adverse events following vaccination.
3. US VACCINE DISTRIBUTION & ADMINISTRATION
- On December 11-12, the US Advisory Committee on Immunization Practices (ACIP) met to approve its interim recommendations for use of the Pfizer/BioNTech SARS-CoV-2 vaccine, following the FDA’s issuance of an EUA. The content of the recommendations, published in the US CDC’s MMWR, provide an update to the initial interim guidance published on December 3.
- ACIP also updated the underlying evidence considered in developing the recommendations. ACIP recommended that the vaccine could be administered to those aged 16 years or older in the US, and that two doses should be administered 21 days apart. ACIP previously also stated that initial doses should be prioritized for healthcare personnel and long-term care facility residents in the first tier of recipients. Notably, the EUA included a provision for pregnant women to potentially be immunized.
- The first shipments of the Pfizer/BioNTech vaccine have already been sent out from Pfizer’s facility in Kalamazoo, Michigan, as well as a distribution center in Wisconsin, and vaccination efforts began across the country.
- Most of the initial reports indicated that healthcare workers were among the first to be vaccinated, as major hospitals are better equipped than many locations to maintain the resource-intensive storage requirements, including that the vaccine be maintained at -112°F (-80°C). Many hospitals will serve as hubs to distribute vaccines locally for long-term care facilities (LCTFs), and there are reports that vaccinations have already commenced at some LCTFs as well.
4. VACCINE COMBINATIONS
- As initial doses of first generation SARS-CoV-2 vaccines are being distributed in some countries, discussions are already underway to optimize second generation vaccine formulations and dosing schedules. Last week, AstraZeneca announced that it is collaborating with the developers of Russia’s Sputnik V vaccine to determine whether administering a combination of the two vaccines could improve efficacy.
- Reportedly, the initial clinical trials of the combination vaccine would be held in Russia to assess this will begin in Russian adults. According to the press release issued by AstraZeneca, the UK government has already announced upcoming clinical trials to evaluate combinations of adenovirus-based vaccines, like those produced by AstraZeneca/Oxford University and Russia’s Gamaleya Research Institute, and mRNA vaccines, like those from Pfizer/BioNTech and Moderna; however, the AstraZeneca and Gamaleya Institute collaboration will evaluate a combination of two adenovirus-based vaccines.
- Utilizing a combination of different vaccines for the same pathogen is called “heterologous boosting,” and it aims to improve both efficacy and accessibility. AstraZeneca indicated that the heterologous boosting approach could speed the process of completing the 2-dose regimen, particularly if the availability of some vaccines is limited; however, UK government health officials stated that the focus is on improving the immune response and not a response to limited supply.
5. EUROPE C19 RESTRICTIONS
- Despite implementing “partial lockdown” measures in early November, Germany is strengthening restrictions ahead of the winter holidays. Germany’s daily incidence has increased tenfold since the beginning of October, and its cumulative incidence increased quadrupled over that time. The magnitude of this “second wave” spurred the German government to take further actions. In the previous partial lockdown, bars and restaurants were closed, while stores and schools remained open.
- In this new “reinforced” lockdown, currently scheduled from December 16 to January 10, schools, retail stores other than grocery stores and supermarkets, and other non-essential businesses will be closed, in addition to bars and restaurants. Businesses that are mandated to close will receive financial support from the government, up to €500,000 (US$600,000) per month. Germany is also implementing household visiting restrictions, with some minor exceptions for Christmas.
- Gatherings will be limited to a maximum of 5 total individuals from 2 households. Over Christmas, including Christmas Eve, households may invite 4 additional people “from the closest family circle.” These celebratory exceptions do not apply to New Year’s Eve. Scheduled New Year’s events are being cancelled, and Germany banned the sale of fireworks. By entering this period of reinforced lockdown, German authorities are hoping to stave off another potential wave that could overwhelm its healthcare system and provide enough time for the European Medicines Agency to authorize a vaccine and vaccination efforts to commence.
- Many areas of the UK are entering the highest tier of C19 restrictions. All boroughs of London as well as areas of Essex and Hertfordshire in England will enter Tier 3 restrictions, which include limitations on indoor and outdoor gatherings and closures for non-essential businesses. A majority of England’s population, 34 million people, will be affected.
- Individuals not living in Tier 3 areas are advised not to travel to and from those areas. A number of the restrictions, including on indoor gatherings, will be relaxed for Christmas celebrations. The UK will permit individuals and families to form a “Christmas bubble”, which will allow individuals from up to 3 households to visit each other indoors and stay overnight. Travel restrictions will also be lifted to allow individuals to visit family members anywhere in the UK.
- Like its neighbor Germany, the Netherlands is also strengthening “lockdown” restrictions ahead of the holiday season. The Dutch government decided to order renewed measures against C19 following a sharp rise in cases over the last 2 weeks. Following a 50% decrease in daily incidence from its second peak, the Netherlands jumped back up 70% since December 1.
- Under the updated restrictions, non-essential businesses must close, schools must switch to remote learning, and gatherings are limited to 2 people, even outdoors. Notably, households will be permitted to have 3 guests indoors from December 24-26, not including children aged 12 years and younger. The Dutch government also outlined “crucial professions” that are permitted to continue in-person operations and noted that children of crucial workers may still attend primary school or after-care programs.
- In contrast to some other European countries, France is taking steps to ease C19 restrictions. After passing its second peak, France ended its “lockdown” today and relaxed some social distancing measures. Rather than a formal lockdown period, France is instituting an 8pm curfew that aims to limit transmission at gatherings at times when people may be less vigilant about implementing appropriate protections, such as physical distancing and mask use.
- After 8pm, most businesses will be directed to close, and individuals will need to carry official exemption certificates in order to be out in public. Violators could face fines of €135, and up to € 3,750 for repeat offenders. Bars, restaurants, and nightclubs are scheduled to remain closed until January 20. The French government will permit individuals and families to travel on December 24 but public gatherings will be prohibited. While the restrictions will be eased slightly for Christmas Eve, France intends to enforce the curfew on January 31, New Year’s Eve.
6. EUROPEAN MEDICINES AGENCY VACCINE AUTHORIZATION
- Following regulatory agencies in Canada, the UK, and the US authorizing the use of Pfizer and BioNTech’s SARS-CoV-2 vaccine, the European Medicines Agency (EMA) is set to complete its assessment by next week. The EMA’s human medicines committee (CHMP) received additional data yesterday and scheduled a meeting for December 21 to discuss its recommendations regarding a conditional authorization.
- Like in other countries, the official determination will be made by the EMA with strong consideration of the CHMP’s recommendations. The meeting was moved forward from December 29, but the CHMP is keeping the originally scheduled meeting on the calendar in the event it is needed. The timing of the CHMP meeting has been criticized as delayed, particularly in light of the authorizations already issued in Canada, the UK, and the US; however, EMA’s Executive Director, Emer Cooke, suggested that the other countries received the clinical trial data earlier than the EMA.
- Reports emerged yesterday that documents related to Moderna’s application for conditional authorization for its candidate SARS-CoV-2 vaccine was accessed via a cyberattack on the EMA. The EMA was also attacked earlier in December, during which hackers gained access to documents related to the Pfizer/BioNTech vaccine as well. Reportedly, the Moderna documents did not include personally identifiable information for study participants.
7. REMDESIVIR & BARICITINIB
- Researchers conducting clinical trials under the Adaptive C19 Treatment Trial 2 (ACCT-2) program published findings from a randomized, placebo-controlled clinical trial evaluating the effect of remdesivir and baricitinib combination therapy for C19. The study, published in NEJM, included more than 1,000 participants divided approximately equally between patients treated with remdesivir and baricitinib and patients treated with just remdesivir (in combination with a placebo).
- The primary analysis focused on time to recovery, and the researchers identified a slight but significant improvement among the treatment group. Patients who received the combination therapy recovered in an average of 7 days, compared to 8 days among the control group. Perhaps most notably, however, the researchers identified an improvement in recovery time from 18 days to 10 days among the 216 patients who received high-flow oxygen therapy or non-invasive ventilation. The researchers indicate that the faster recovery time among these patients with severe disease could be a result of reduced risk of hospital-acquired infections and thrombosis.
8. GUILLAIN-BARRÉ SYNDROME
- Researchers in the UK published findings from a study on Guillain-Barré syndrome (GBS) and C19. GBS is a relatively rare neurological condition that can develop following various kinds of infections, including viral, and some have speculated that C19 could be driving an increase in GBS. GBS can cause pain and numbness and even muscle weakness or paralysis in severe cases. If the weakness or paralysis affects the muscles responsible for breathing, it could be fatal, and patients could require mechanical ventilation.
- The GBS study, published in Brain, found no causative association between GBS and C19. The researchers compared GBS data during the UK’s first C19 wave (March-May 2020) against GBS data from 2016-19. Like many other health conditions, reports of GBS decreased during the first wave, falling from 113-132 cases in March-May in 2016-19 to 56-93 cases in 2020. This could be a result of individuals delaying medical care during the UK’s “lockdown” or a reduction in transmission of other infections that could lead to GBS.
- The researchers also included seroprevalence data for SARS-CoV-2 infection among blood donors, and they estimate the risk of GBS to be approximately 0.016 cases of GBS per 1,000 cases of C19. The researchers also evaluated patient-level data from 47 GBS cases reported in the UK, including 13 confirmed and 12 probable C19 cases and 22 non-C19 patients. They identified an increase in the use of intubation among GBS patients with C19, which the researchers believe is “likely” due to the pulmonary effects of C19 rather than increased severity of GBS presentation.
- GBS has previously been identified following vaccination, with frequency estimates ranging from occasional to rare. Following influenza vaccination efforts in the US in 1976-77, reports of GBS in recently vaccinated individuals ultimately resulted in the suspension of vaccination activities, and this historical example has contributed to concerns about links between vaccination and GBS. In light of the UK and other countries commencing SARS-CoV-2 vaccination efforts, the research study was published alongside a commentary regarding the risk of GBS associated with SARS-CoV-2 vaccination.
- The commentary—authored by researchers from the Netherlands, Spain, the UK, and the US—called on health and elected officials to resist the urge to link GBS cases after vaccination to the vaccine. The researchers outline approximations for expected incidence of GBS under normal conditions, and they conclude that normal GBS incidence would result in more than 13,000 cases globally in the 10 weeks following a SARS-CoV-2 vaccination, without any effect at all from the vaccine.
- They use this analysis to highlight that many individuals will inevitably develop GBS, whether they are vaccinated or not, and a substantial portion of these cases will, by pure coincidence, develop in the period after vaccination. It is critically important to closely monitor for adverse events, but it is just as important to ensure that we do not unnecessarily suspend vaccination activities as a result of preconceived notions regarding the risk of GBS or other conditions.