October 22, 2020
Without reliable information, we rely on fear or luck.
“Imagine if the COVID vaccine doesn’t work and this is our future, because it is a real possibility.”Michael Every, Head of Financial Markets Research, Asia-Pacific at Rabobank
“If it weren’t for the CDC ban, my kids and I would be homeless.”Natasha Burns, a struggling American who owes more than $7,000 of back rent
“A vicious circle of stop-go lockdowns would be a catastrophic indictment of Government policy, an admission of total defeat, a victory of fear and emotion over reason, an appalling signal that Britain has now become so culturally dysfunctional, so decadent as to be utterly incapable of any rational cost-benefit analysis.”Allister Heath, Editor of The Sunday Telegraph
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
5. Pandemic fatigue and a new wave
1. What will winter bring?
N. Linked Stories
(Non-pharmaceutical interventions such as voluntary shelter-in-place, quarantines, and other steps taken to control the coronavirus can reduce the peak number of infections, daily infection rates, total infections, and overall deaths)
6. University of Minnesota trial shows hydroxychloroquine does not prevent C19 in health care workers [Note: For an analysis of all hydroxychloroquine studies and trails, see c19study.com]
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A. The Pandemic As Seen Through Headlines
(In no particular order)
- Coronavirus is currently the 13th deadliest pandemic in world history
- The worst of the coronavirus pandemic could still be to come
- Hispanics see highest increase in COVID-19 deaths over summer, CDC report finds
- Promising antibody treatments will be in short supply
- Leaders in US, Europe divided on response to surging coronavirus
- Trump says ‘not much’ he could have done differently with COVID-19
- New surge of Covid-19 cases has states, hospitals scrambling
- Deaths rates among hospitalized COVID-19 patients declining: report
- Economy-Crushing COVID-19 Lockdowns Contributed To 100,000 US Deaths, New CDC Guidance Suggests
- Dozens to be deliberately infected with coronavirus in UK ‘human challenge’ trials
- The Chinese city of Yiwu stopped the sale of a coronavirus vaccine after dozens of people demanded to be inoculated, underlining the popularity of a vaccine that has not even completed late-stage clinical trials
- Patient In AstraZeneca COVID-19 Vaccine Trial That Died Received a Placebo (Not the Vaccine)
- AstraZeneca’s COVID vaccine trial may resume in the US this week
- NYC unveils vaccination plan
- CA Gov. Newsom Casts Doubt on FDA-Approved Virus Vaccine: ‘Don’t Take Anyone’s Word for It’
- California Will Independently Test Coronavirus Vaccines
- Most people would get COVID-19 vaccine if offered by government or employer
- Some COVID-19 vaccines could increase risk of HIV
- New York’s COVID-19 Mandatory Quarantine List Climbs To 43 States
- NY new cases top 2,000 for first time since May
- NY Gov. Cuomo urges tri-state residents to avoid travel between states unless ‘essential’
- ‘New York Tough’ isn’t going to get us through the pandemic
- Peru has the toughest lockdown in the world and still ended up with the worst fatality rate
- ‘Swedish Fauci’ still won’t budge on no-mask approach despite rising COVID-19 cases
- Ireland Becomes First EU Country to Re-Enter Full Lockdown as Europe Battles COVID Second Wave
- Wales imposes two-week lockdown: ‘everybody must stay at home’
- About seven million people in the north of England will soon be living under the country’s toughest virus restrictions in Britain’s new tiered response system
- ‘Dumb Bastards’ — President Trump Rips CNN for Pushing Coronavirus Panic
- As world grapples with the coronavirus pandemic, the Ebola virus is raging
- Coronavirus vaccines stir doubts among many people worldwide
- Judge reinstates Wisconsin Governor’s restaurant and bar closure order
- Boston suspended in-person learning in public schools, citing the city’s rising tide of cases
- Pennsylvania governor vetoes bill to reopen state’s restaurants at full capacity
- Florida Gov. DeSantis slams school closure idea, says it’s ‘off the table’
- University of Michigan students ordered to stay in place amid COVID-19 spike
- US-Canada-Mexico borders to remain closed as coronavirus persists
- Facing a second wave of the virus, some people in New York City are stockpiling supplies — even as Gov. Andrew Cuomo eased some restrictions in certain neighborhoods
- People are buying fire pits, pianos to prepare for the second COVID-19 wave
- Swamped with virus cases, North Dakota suspends contact tracing
- In the past seven days, seven countries — Argentina, Brazil, Britain, France, India, Russia and the U.S. — have each reported at least 100,000 new cases of the coronavirus, helping to push total cases worldwide to more than 40.7 million.
- Spain becomes sixth country to top 1 million COVID-19 cases
- WHO blames poor quarantine enforcement for COVID-19 resurgence
- Pfizer has recruited nearly 40,000 for vaccine trial
- Bar, restaurant closures in Belgium begin
- Italy announces new restrictions
- Moscow Mayor resists return to lockdown
- Bavaria imposes localized lockdown
- Iran breaks one-day record for COVID-19 deaths again
- Ireland announces new fines for violating lockdowns
- Belgium overtakes Netherlands as worst hit country last week
- The Czech Republic, the country that had the highest coronavirus transmission rates in Europe in mid-October, announced plans to close most shops and further tighten restrictions on movement
- India sees lowest new cases in 3 months
- Kansas nursing home sees all its patients infected
- Moderna CEO says expects to apply for FDA EUA in December
- Australia sees another shipborne outbreak
- Russia outbreak worsens
- Argentina tops 1 million cases, 5th country to do so
- Thailand welcomes its first foreign tourists in months
- Singapore Airlines to resume non-stop flights to NY
- Chinese officials in Qingdao claim to have detected live virus on frozen food packaging
- EU to link national COVID-19 tracing apps together
- COVID-19 pandemic drives innovation in diabetes care
- Could Obesity Thwart a Vaccine?
- 50,000 Children’s Surgeries Postponed, Deaths on Transplant Waiting List Near-Doubled Due to Lockdown
- US overdose deaths appear to rise amid coronavirus pandemic
- The Virus Can Kill Your Sense of Smell. That’s More Devastating Than It Sounds
- Million New Yorkers Can’t Afford Food As Hunger Crisis Worsens
- “January Is Going To Be A Mess” – A Tsunami Of Evictions Expected Across US
- Greenwich Home Sales Have Best Quarter “In A Decade” As New York City Exodus Continues
- Rich New Yorkers flee to Hamptons, sparking $1 billion real estate boom
- CVS Health announced that it planned to hire 15,000 workers to prepare for expected increases in coronavirus and flu cases in the coming months
- 1 in 4 US workers have considered quitting their job amid pandemic
- TSA Passenger Traffic Tops One Million Sunday As Return To Normalcy Continues
- US sees busiest day for air travel since the start of COVID-19
- Homebuilder Sentiment Soars To New Record High
- Trump: US would be in ‘massive depression’ if I listened to experts
- Athletes Are Struggling With Mental Health Amid Shutdowns
- A cluster of coronavirus cases in a rural area of Switzerland may be linked to two yodeling concerts that attracted hundreds of unmasked spectators at the end of September
- Europe’s museums are open, but the public isn’t coming
- Whole Foods launches free one-hour grocery pickup at all US stores
- Netflix says COVID-19 won’t delay most 2021 releases
- Study shows women take COVID-19 more seriously than men
- UK condom sales surge after coronavirus lockdown ends
- Polish gym declares itself a church to avoid coronavirus restrictions
- A frozen yogurt shop in Colorado offered maskless customers a 10% discount. Uproar ensued.
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 = 41,462,048
- New Cases = 437,050
- New Cases (7 day average) = 385,993 (+7,797) (+2.1%)
- Number of new cases is a record high
- 7 day average of new cases is a record high
- 1,000,000 new cases every 2.6 days
US Cases & Testing:
- Total Cases = 8,584,819
- New Cases = 63,663
- New Cases (7 day average) = 61,489 (+573) (+0.9%)
- Percentage of New Global Cases (7 day average) = 16.5%
- Total Number of Tests = 128,650,157
- Percentage of positive tests (7 day average) = 6.5% (+1.4% since 10/1)
- 7 day average of new cases is rapidly increasing
- Since 9/26, the 7 day average has increased from 41,580 to 61,489, an increase of 47.9%
- 7 day average of the percentage of positive tests is also increasing
- The increase in 7 day average of new deaths and positives tests foreshadows an increase in deaths (and the 7 day average has started to increase significantly)
- Total Deaths = 1,135,697
- New Deaths = 6,849
- New Deaths (7 day average) = 5,639 (+110) (+2.0%)
- 7 day average of new deaths has been mostly rising since 10/3
- 7 day average of new deaths has been rapidly increasing since 10/13
- The peak of new deaths occurred on 4/18, at which time the 7 day average of new deaths was 7,071
- At the peak, the confirmed case fatality rate was 9.3%
- As of 10/21, the confirmed fatality rate is 1.5%, a decline of 83.9% since the peak
- Total Deaths = 227,409
- New Deaths = 1,225
- New Deaths (7 day average) = 794 (+36) (+4.6%)
- Percentage of Global New Deaths (7 day average) = 11.6%
- 7 day average of new deaths has increased from 704 on 10/17 to 794, an increase of 12.8%, which is a worrisome trend
- The peak of new deaths occurred on 4/21, at which time the 7 day average of new deaths was 2,256 (more than 3x the current 7 day average)
- At the peak, the confirmed case fatality rate was 7.7%
- As of 10/21, the confirmed fatality rate is 1.4%, a decline of 81.8% since the peak
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (10/21)
- The positivity rate continues to rise across the country
- Nationally, the average 7-day positivity rate was 6.5% — an increase from the 5.2% 7-day average positivity rate as of 10/7.
- ND, SD, ID WI, and KS had 7-day positivity rates greater than 20%.
- In total, 37 states have 7-day positivity rates greater than 5% (+4 states since 10/7)
- Hospitalizations in the US increased to 40,271. This is the first time since 8/21 that hospitalizations have been greater than 40,000
- TX hospitalizations have reached their highest level since 8/26
- CA (ranked #2) hospitalizations have declined 4% since 10/4
4. ‘At a breaking point’: New surge of C19 cases has states, hospitals scrambling, yet again
- As hospitalizations for C19 inch up around the country, some states are readying plans for field hospitals. Communities are delaying reopening plans and even imposing new measures, though some governors remain opposed to additional restrictions. Deaths — currently standing about 220,000 — have not surged again yet, but that might just be a matter of time.
- The current rise in coronavirus cases around the U.S. is reminiscent of the summer crest, and has flashbacks to the emergence of the national crisis in the spring. There are attempts to characterize what’s happening — a third wave or a third peak of a single wave that never fully ebbed — but whatever your semantic preference, cases are racing up in many states and breaking daily records in the Midwest and Mountain West. They’re even creeping up in places that experienced the brunt of the earlier outbreaks, like Massachusetts and New York.
- “We thought it was horrible then, but when you look at it from this perspective, they were fairly low,” said Kimberley Shoaf, an expert in public health crises at the University of Utah, reflecting on her state’s caseload in the spring. Now, for the first time, Utah is consistently seeing more than 1,000 new daily infections, according to STAT’s C19 Tracker.
- “Our health care system is almost at a breaking point,” Shoaf said.
- Experts had warned that the country needed to take steps at the end of the summer and the beginning of the fall to make headway in suppressing its infection rate. They expect transmission to pick up as temperatures drop and the winter arrives, both because of behavioral changes (people spending more time indoors and having contact with more people) and because they anticipate that the virus will spread even more efficiently in cold, dry weather.
- Instead, cases have gone in the other direction, already starting to increase and portending even more dire months ahead.
- Seven months into the eye of the U.S. epidemic, people are tired of the precautions meant to slow the spread of the coronavirus (SARS-CoV-2). But slipups and relaxed attitudes are in turn driving new illnesses. Deborah Birx, the physician coordinating the White House’s coronavirus efforts, has cited social and family gatherings where people let their guards down as burgeoning sites of spread.
- The fundamental transmission of the virus hasn’t changed. The virus will go where it’s given room to run, and will find people who are susceptible there. Despite over 8 million confirmed U.S. cases, the vast majority of Americans — up to 90% according to federal estimates — remains vulnerable to an infection. (The thought is that generally people who recover from C19 will be protected from another case for some amount of time.)
- It’s difficult to compare directly where the epidemic stands versus March or July, given that the continued expansion of testing means that a greater proportion of cases are being diagnosed now than before. The geography of the outbreak is also different, with many new cases occurring outside dense cities that inculcated spread in the spring.
- But the raw numbers are deeply worrying. Last week, the country hit 70,000 daily cases for the first time since July. The new climb in cases also started from a higher point than the summer peak did; with more virus circulating, it’s more likely that some cases will spark new chains of transmission or that superspreading events will occur.
- The latest surge also comes as more people are going back to work and school. Universities are finding that the precautions taken in classrooms and dining halls — masks, limited capacities, physical distancing, and the like — seem to be working for the most part, but, reflecting the broader U.S. outbreak, it is student gatherings that are fueling outbreaks in residence halls and Greek houses.
- “What we’re seeing with each passing week is that social gatherings are the risk, not simply living in these settings,” said Preeti Malani, an infectious disease physician and chief health officer at the University of Michigan.
- Like in the outbreaks in Texas and Florida over the summer, younger adults appear to be accounting for a bulk of new infections, which, in a way, is a positive sign, given that they are less likely to have severe cases or die than older adults. But thinking that spread among younger adults is harmless ignores the fact that some of them will still die or get very sick, straining the health care system. Plus, if the virus is spreading among a certain population, it won’t stay there. A Centers for Disease Control and Prevention study released this month showed how rising infections among people ages 20 to 39 preceded an increase in cases among people 60 years and older — a trend that “is likely to result in more hospitalizations, severe illnesses, and death,” the researchers wrote.
- “Infection spreads,” said Stephen Kissler, an epidemiologist at Harvard’s T.H. Chan School of Public Health. If younger people are getting infected now, he said, “ultimately, what that will mean is that there will probably be a longer delay between the observed cases and, for example, hospitalizations and deaths, because there have to be a couple extra chains of transmission between the people who are first getting infected and then getting the disease passed onto the people who are going to be most strongly affected.”
- It’s a reminder that the data points we look at to gauge the severity of outbreaks are inherently outdated. Cases that are diagnosed now reflect spread that occurred probably a week ago. People who are being hospitalized now typically contracted the coronavirus two weeks ago. It will take another two weeks or so for those who will die from C19 to succumb. It all means that the effect of any new measures to stop the spread of the virus won’t be reflected in those data points for some time.
- But those interventions — including those far short of full lockdowns — can work, experts are increasingly finding. In Arizona, for example, daily cases exploded by 151% in just two weeks in June after the state’s stay-at-home order was lifted. Eventually, however, the state allowed for local mask mandates, reclosed some businesses like bars, and restricted public events, helping drive cases down by 75% over a few weeks in July and August, according to a study from CDC and Arizona health officials. It’s why public health officials have been stressing that relatively simple measures — such as masks, avoiding crowds, reducing opportunities for superspreading, maintaining distancing, and hand hygiene — can stave off a sizable amount of transmission.
- The fact that the epidemic is now hitting states like the Dakotas and Montana so hard reflects what experts envisioned at the outset of the U.S. crisis. The virus would spread the most at first in dense cities that received a high number of imported cases, and from there would travel to other cities, and then trickle to more rural areas.
- “Slowly, day after day, you’ve seen the gap in the infection rates decline” between metropolitan areas and rural areas, said Fred Ullrich, a program director at the University of Iowa’s College of Public Health. It might be a combination of a better handle on the virus in cities or a more lax approach in rural areas, “but we’re seeing it all over the Midwest, and all over the United States.”
- The spread of the virus now is more diffuse than in the spring, when it was so walloping in places like the Northeast or New Orleans. Clinicians have also gotten better at treating C19 patients over the past months. But experts warn that local surges could still overwhelm health systems, exacerbating staffing shortages, imperiling patient care, and potentially leading to worse outcomes.
- “When your health care capacity isn’t sufficient to meet demand, you’re going to see higher fatalities,” Shoaf said.
- There is one aspect of U.S. reopening plans that experts, if you ask them how it’s going, will say they’re “encouraged” about: K-12 schools. The available data, including from a dashboard put together by researchers at Brown University and colleagues, indicates that schools aren’t experiencing frequent widespread outbreaks.
- But experts are also cautious about simply declaring in-person schooling safe. The data that do exist are generally voluntarily supplied by districts, so it’s not clear what’s missing. Because there’s no national reporting, researchers can’t parse which approaches — hybrid models, mask mandates, classroom size restrictions, limiting in-person instruction to just the youngest students while having middle and high schoolers learn virtually — are working best in terms of minimizing cases.
- “It is encouraging, there’s no doubt about that,” Wendy Armstrong, an infectious disease physician at Emory University, said about the K-12 school experience so far. But having such limited information available “severely limits our ability to give additional guidance to schools that are based on very clear, evidence-based data. And with limited reporting, in my mind, it makes it impossible to interpret the available data to truly understand current risk.”
- Armstrong pointed to one point of success so far. Teachers and parents wondered if young students would tolerate wearing masks while they were in school. So far, Armstrong said, it seems like the kids are doing all right.
5. Pandemic fatigue and a new wave
- Coronavirus cases in the United States are surging toward their third peak in eight months. More than 70,000 new infections were recorded last Friday, the most in a single day since July, and the country recently surpassed eight million total cases.
- How did we get here — again?
- If the summer surge was driven by states that quickly reopened their economies without meeting safety benchmarks, this latest wave may be attributed in part to impatience of a different kind.
- The communal rituals of hope that helped people endure the initial outbreak have given way to exhaustion and frustration. And with no end to the pandemic in sight, a public weariness is sinking in, sending people flocking to bars, family parties, bowling alleys and sporting events.
- The same dynamic is playing out in Europe, which had largely beaten back the virus with harsh lockdowns in the spring, but is now facing a terrifying new wave. Countries across the continent are announcing fresh restrictions at a time when researchers from the World Health Organization estimate that about half of the population is experiencing “pandemic fatigue.”
- For Europe and the U.S. alike, the dangerous combination of apathy and soaring coronavirus cases may exacerbate what already threatens to be a devastating autumn. In the United States, case counts are on the rise in 41 of the 50 states, with devastating surges in the Great Lakes and Great Plains regions, along with major outbreaks in the Midwest and Rocky Mountains.
- The situation couldn’t be more different in areas of the world that have managed to keep infection rates low for months. In China, South Korea, Japan, New Zealand and Australia, people changed their behavior, and containment measures have been strict and effective. In many instances, people in those countries have complained that their governments haven’t gone far enough to contain the virus.
- Fortunately, the fall resurgence arrives at a time when mask use is widespread, personal protective gear is more available, medical treatments are more sophisticated and deaths remain lower — for now.
Source: New York Times Coronavirus Briefing
C. New Scientific Findings & Research
1. Studies Point To Big Drop In C19 Death Rates
- Two new peer-reviewed studies are showing a sharp drop in mortality among hospitalized C19 patients. The drop is seen in all groups, including older patients and those with underlying conditions, suggesting that physicians are getting better at helping patients survive their illness.
- “We find that the death rate has gone down substantially,” says Leora Horwitz, a doctor who studies population health at New York University’s Grossman School of Medicine and an author on one of the studies, which looked at thousands of patients from March to August.
- The study, which was of a single health system, finds that mortality has dropped among hospitalized patients by 18 percentage points since the pandemic began. Patients in the study had a 25.6% chance of dying at the start of the pandemic; they now have a 7.6% chance.
- That’s a big improvement, but 7.6% is still a high risk compared with other diseases, and Horwitz and other researchers caution that C19 remains dangerous.
- The death rate “is still higher than many infectious diseases, including the flu,” Horwitz says. And those who recover can suffer complications for months or even longer. “It still has the potential to be very harmful in terms of long-term consequences for many people.”
- Studying changes in death rate is tricky because although the overall U.S. death rate for C19 seems to be dropping, the drop coincides with a change in whom the disease is sickening.
- “The people who are getting hospitalized now tend to be much younger, tend to have fewer other diseases and tend to be less frail than people who were hospitalized in the early days of the epidemic,” Horwitz says.
- So have death rates dropped because of improvements in treatments? Or is it because of the change in who’s getting sick?
- To find out, Horwitz and her colleagues looked at more than 5,000 hospitalizations in the NYU Langone Health system between March and August. They adjusted for factors including age and other diseases, such as diabetes, to rule out the possibility that the numbers had dropped only because younger, healthier people were getting diagnosed. They found that death rates dropped for all groups, even older patients by 18 percentage points on average.
- The research, an earlier version of which was shared online as a preprint in August, will appear next week in the Journal of Hospital Medicine.
- “I would classify this as a silver lining to what has been quite a hard time for many people,” says Bilal Mateen, a data science fellow at the Alan Turing Institute in the United Kingdom. He has conducted his own research of 21,000 hospitalized cases in England, which also found a similarly sharp drop in the death rate. The work, which will soon appear in the journal Critical Care Medicine and was released earlier in preprint, shows an unadjusted drop in death rates among hospitalized patients of around 20 percentage points since the worst days of the pandemic.
- Mateen says drops are clear across ages, underlying conditions and racial groups. Although the paper does not provide adjusted mortality statistics, his rough estimates are comparable to those Horwitz and her team found in New York.
- “Clearly, there’s been something [that’s] gone on that’s improved the risk of individuals who go into these settings with C19,” he says.
- Horwitz and others believe many things have led to the drop in the death rate. “All of the above is often the right answer in medicine, and I think that’s the case here, too,” she says.
- Doctors around the country say that they’re doing a lot of things differently in the fight against C19 and that treatment is improving. “In March and April, you got put on a breathing machine, and we asked your family if they wanted to enroll you into some different trials we were participating in, and we hoped for the best,” says Khalilah Gates, a critical care pulmonologist at Northwestern Memorial Hospital in Chicago. “Six plus months into this, we kind of have a rhythm, and so it has become an everyday standard patient for us at this point in time.”
- Doctors have gotten better at quickly recognizing when C19 patients are at risk of experiencing blood clots or debilitating “cytokine storms,” where the body’s immune system turns on itself, says Amesh Adalja, an infectious disease, critical care and emergency medicine physician who works at the Johns Hopkins Center for Health Security.
- He says that doctors have developed standardized treatments that have been promulgated by groups such as the Infectious Diseases Society of America.
- “We know that when people are getting standardized treatment, it makes it much easier to deal with the complications that occur because you already have protocols in place,” Adalja says. “And that’s definitely what’s happened in many hospitals around the country.”
- But Horwitz and Mateen say that factors outside of doctors’ control are also playing a role in driving down mortality. Horwitz believes that mask-wearing may be helping by reducing the initial dose of virus a person receives, thereby lessening the overall severity of illness for many patients.
- And Mateen says that his data strongly suggest that keeping hospitals below their maximum capacity also helps to increase survival rates. When cases surge and hospitals fill up, “staff are stretched, mistakes are made, it’s no one’s fault — it’s that the system isn’t built to operate near 100%,” he says.
- For these reasons, Horwitz and Mateen believe that masking and social distancing will continue to play a big role in keeping the mortality rate down, especially as the U.S. and U.K. move into the fall and winter months.
- Gates adds that the takeaway definitely should not be to cast the mask aside. There is still no cure for this disease, and even patients who recover can have long-term side effects. “A lot of my patients are still complaining of shortness of breath,” she says. “Some of them have persistent changes on their CT scans and impacts on their lung functions.”
- And many people will continue to die, even if the rate has dropped. A recent estimate by the Institute for Health Metrics and Evaluation suggests the total death count could reach well over 300,000 Americans by February.
- “I do think this is good news,” Horwitz says of her research findings, “but it does not make the coronavirus a benign illness.”
2. Breakthrough study identifies why C19 is highly infectious
- In a major breakthrough an international team of scientists led by the University of Bristol, has potentially identified what makes the coronavirus (SARS-CoV-2) highly infectious and able to spread rapidly in human cells. The findings, published in Science today [20 October] describe how the virus’s ability to infect human cells can be reduced by inhibitors that block a newly discovered interaction between virus and host, demonstrating a potential anti-viral treatment.
- Unlike other coronavirus, which cause common colds and mild respiratory symptoms, SARS-CoV-2 is highly infective and transmissive. Until now, major questions have remained unanswered as to why SARS-CoV-2 readily infects organs outside of the respiratory system, such as the brain and heart.
- To infect humans, SARS-CoV-2 must first attach to the surface of human cells that line the respiratory or intestinal tracts. Once attached, the virus invades the cell then replicates multiple copies of itself. The replicated viruses are then released leading to the transmission of SARS-CoV-2.
- The virus’s process of attachment to and invasion of human cells is performed by a viral protein, called the ‘Spike’ protein. Understanding the process by which the ‘Spike’ protein recognizes human cells is central to the development of antiviral therapies and vaccines to treat C19.
- In this breakthrough study, the research groups in Bristol’s Faculty of Life Sciences, Professor Peter Cullen from the School of Biochemistry; Dr Yohei Yamauchi, Associate Professor and virologist from the School of Cellular and Molecular Medicine, and Dr Boris Simonetti, a senior researcher in the Cullen lab, used multiple approaches to discover that SARS-CoV-2 recognizes a protein called neuropilin-1 on the surface of human cells to facilitate viral infection.
- Yohei, Boris and Pete explained: “In looking at the sequence of the SARS-CoV-2 Spike protein we were struck by the presence of a small sequence of amino acids that appeared to mimic a protein sequence found in human proteins which interact with neuropilin-1. This led us to propose a simple hypothesis: could the Spike protein of SARS-CoV-2 associate with neuropilin-1 to aid viral infection of human cells? Excitingly, in applying a range of structural and biochemical approaches we have been able to establish that the Spike protein of SARS-CoV-2 does indeed bind to neuropilin-1.
- “Once we had established that the Spike protein bound to neuropilin-1 we were able to show that the interaction serves to enhance SARS-CoV-2 invasion of human cells grown in cell culture. Importantly, by using monoclonal antibodies – lab-created proteins that resemble naturally occurring antibodies – or a selective drug that blocks the interaction we have been able to reduce SARS-CoV-2’s ability to infect human cells. This serves to highlight the potential therapeutic value of our discovery in the fight against C19.”
- Intriguingly, scientists at the Technical University of Munich, Germany and the University of Helsinki, Finland, have independently found that neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.
- Together the Bristol researchers concluded: “To defeat C19 we will be relying on an effective vaccine and an arsenal of anti-viral therapeutics. Our discovery of the binding of the SARS-CoV-2 Spike to neuropilin-1 and its importance for viral infectivity provides a previously unrecognised avenue for anti-viral therapies to curb the current C19 pandemic.”
3. Researchers Identify How to Predict Cytokine Storm in C19 Patients
- Like a cold front that moves in, setting the stage for severe weather, coronavirus infection triggers showers of infection-fighting immune molecules — showers that sometimes escalate into a chaotic immune response known as a cytokine storm. About 20 to 30%t of patients hospitalized with C19 develop severe immune manifestations, in some instances leading to cytokine storm, with life-threatening organ damage and high risk of death.
- Predicting which C19 patients will develop cytokine storm is challenging, owing to the many variables that influence immune function. But now, in breakthrough work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) have developed and validated predictive criteria for early identification of C19 patients who are developing hyperimmune responses, raising the possibility for early therapeutic intervention.
- “If we can anticipate cytokine storm, we can apply treatment sooner and possibly decrease mortality,” explained Roberto Caricchio, MD, Chief of the Section of Rheumatology, Director of the Temple Lupus Program, Professor of Medicine and Microbiology and Immunology at LKSOM, and lead author on the new report.
- The report, published online in the Annals of the Rheumatic Diseases, is the first to identify criteria that can be readily used in clinical practice to potentially head off the worst of the hyperimmune attack against C19.
- The breakthrough is the result of an extensive collaboration between researchers and clinicians across multiple departments in the Lewis Katz School of Medicine and Temple University Hospital, constituting the Temple University C19 Research Group.
- According to Dr. Caricchio, large numbers of C19 patients have been treated at Temple since the pandemic emerged in the United States. “We have a significant amount of data in terms of variables to predict cytokine storm,” he said.
- Since early March, every patient admitted to Temple University Hospital (TUH) has had data on more than 60 different laboratory variables collected daily until the time of recovery or time of death. Among variables measured every day are factors like white blood cell count, metabolic enzyme activity, and markers of inflammation and respiratory function. Importantly these markers are commonly used in hospitals across the globe and therefore are readily available.
- The research group carried out statistical analyses on laboratory data for 513 C19 patients hospitalized at TUH in March and April, 64 of whom developed cytokine storm. A genetic algorithm was used to identify cut-off values for each individual laboratory variable to define the predictive requirements for cytokine storm. Genetic algorithms mimic the processes of natural selection and evolution in analyzing the data, and in this case, over multiple iterations, the algorithm turned up variables indicating which patients are most likely to develop cytokine storm.
- Overall, the analyses yielded six predictive criteria comprising three clusters of laboratory results relating to inflammation, cell death and tissue damage, and electrolyte imbalance. In particular, patients in cytokine storm exhibited a proinflammatory status and elevated levels of enzymes indicating significant systemic tissue damage. Moreover, patients who met the criteria had extended hospital stays and were at increased risk of death from C19, with almost half of patients who experienced cytokine storm meeting all criteria within the first day of hospitalization.
- The researchers validated the criteria in a subsequent cohort of 258 patients admitted to TUH for C19 infection. “The algorithm correctly predicted cytokine storm in almost 70 percent of patients,” Dr. Caricchio said.
- “The ability to reproduce our results in a second cohort of patients means that our group of variables are effective criteria for cytokine storm diagnosis in C19 patients,” he added. The final step now is to have the criteria validated by other centers where C19 patients are admitted for care.
- Dr. Caricchio noted that the criteria could be applied to C19 patients at any hospital or level of hospitalization anywhere in the world. “This makes the criteria very valuable for guiding decisions about how to treat C19 patients worldwide,” he said. Applied more broadly, the criteria could greatly facilitate early diagnosis and intervention, helping save many lives.
- “This was a truly collective effort between frontline clinicians, researchers, and statisticians, and the results are one of the many testaments to the exceptional work Temple University and the Temple University Health System have performed,” Dr. Caricchio concluded.
4. Severity of C19 may be linked to molecular sources
- People have different susceptibilities to the coronavirus (SARS-CoV-2) and develop varying degrees of fever, fatigue, and breathing problems — common symptoms of the illness. What might explain this variation?
- Scientists at the University of California, Riverside, and University of Southern California may have an answer to this mystery.
- In a paper published in Informatics in Medicine Unlocked, the researchers show for the first time that the observed C19 variability may have underlying molecular sources. The finding could help in the development of effective prophylactic and therapeutic strategies against the disease.
- “Based on biomarkers and molecular profiles of individuals, one would hope to develop better medical tests to accommodate these variations in monitoring virus transmission and disease pathology, which helps guide mitigation and treatment options,” said Sika Zheng, an associate professor of biomedical sciences at the UC Riverside School of Medicine, who led the study.
- The SARS-CoV-2 virus hijacks human host molecules for fusion and virus replication, attacking human cellular functions. These human host molecules are collectively called SARS-CoV-2 host genes. The researchers systematically analyzed SARS-CoV-2 host gene expression, their variations, and age- and sex-dependency in the human population using large-scale genomics, transcriptomics, and proteomics.
- They first found similarity of host gene expression is generally correlated with tissue vulnerability to SARS-CoV-2 infection. Among the six most variably expressed genes in the population they identified ACE2, CLEC4G, and CLEC4M, which are known to interact with the spike protein of SARS-CoV-2. Higher expression of these genes likely increases the possibility of being infected and of developing severe symptoms. Other variable genes include SLC27A2 and PKP2, both known to inhibit virus replication; and PTGS2, which mediates fever response. The authors also identified genetic variants linked to variable expression of these genes.
- According to the Zheng, the expression profiles of these marker genes may help better categorize risk groups.
- “More comprehensive risk assessment can better guide the early stage of vaccine distribution,” he said. “Tests can also be developed to include these molecular markers to better monitor disease progression. They can also be used to stratify patients to assess and ultimately enhance treatment effectiveness.”
- In addition to identifying the most variable SARS-CoV-2 host genes, results from the study suggest genetic and multiple biological factors underlie the population variation in SARS-CoV-2 infection and symptom severity.
- “Of course, these will need confirmation with more data. But the results indicate a potential value of a large scale eQTL project to profile genotypes and transcriptome of C19 patients,” Zheng said.
- Next, the researchers plan to further analyze large scale genotypes and transcriptome data of C19 patients when made available and to refine the results for higher association and accuracy.
5. C19 cough clouds in closed spaces
- As the coronavirus has affected more than 30 million people globally, researchers have increasingly focused on the extent to which airborne respiratory droplets carrying the virus travel and contaminate the air after an infected person coughs.
- While scientists have studied the properties of air at the mouth, such as volume, temperature, droplet distribution, and humidity, less is known about how these properties change as the cough cloud travels. In Physics of Fluids, by AIP Publishing, researchers estimate the evolving volume of the cough cloud and quantify the reduction in its volume in the presence of a face mask.
- “We estimate this volume of the air, which may help to design ventilation of closed spaces and consequently reduce the spread of the disease,” said Amit Agrawal, one of the authors.
- The researchers also examined the variation in temperature and humidity in the cough cloud as the determinant that impacts the droplet distribution in the cloud.
- Using an analysis based on jet theory and experimental data from the literature, they found that it’s the first 5 to 8 seconds after coughing that matter for suspending the exhaled droplets in the air and, consequently, for the spread of the disease. After that time, the cough cloud typically starts to disperse.
- The scientists found the cloud volume without a mask is about 7 times larger than with a surgical mask and 23 times larger than with an N95 mask.
- “We found that anything that reduces the distance traveled by the cloud, such as a mask, handkerchief, or coughing into an elbow, should greatly reduce the region over which the droplets disperse upon coughing and therefore the chances of infection,” said Rajneesh Bhardwaj, another author.
- Interestingly, the researchers found how hard a person coughs, which impacts the initial velocity and volume of coughing, does not affect the volume in the cough cloud when the person is not wearing a mask, although the initial volume is very important for a person wearing a mask.
- The scientists determined the volume of a cough cloud varies as a cube of the total distance traveled by the cloud with the proportionality constant being 1 to 150. This formula will be helpful in determining the maximum number of people that can be accommodated in a hospital ward, and the minimum rate at which air in a room, elevator, cinema hall, car, aircraft cabin, or restaurant needs to be circulated to maintain freshness and reduce the chance of infection.
D. Vaccines & Testing
1. How obesity could create problems for a COVID vaccine
- When Jesús Ojino Sosa-García looks out over the people being treated for C19 in his hospital’s intensive-care unit, one feature stands out: “Obesity is the most important factor we see,” he says.
- Sosa-García works at Hospital Médica Sur in Mexico City, which has been battling a C19 outbreak for six months. “Every day, we receive patients,” he says. And many of those showing up with severe cases come from Mexico’s growing population of obese individuals — currently 36% of adults. Sosa-García and his colleagues checked the stats early in the pandemic and they were already indicating an imbalance: half of the 32 people admitted to his hospital’s intensive-care unit with severe C19 before 3 May were obese.
- Sosa-García is optimistic that a coronavirus vaccine will arrive soon to dampen the pandemic. But for Mexico and many other countries with a burgeoning population of people with high body mass indices (BMIs), some researchers fear that a vaccine might not be the panacea Sosa-García is hoping for. Obesity correlates with a dulled immune response to C19. And vaccines for a handful of other conditions often don’t work as well in obese people, suggesting that a shot for C19 might not provide as much protection as researchers would like. “We worry about that,” says Donna Ryan, who has studied obesity at the Pennington Biomedical Research Center in Baton Rouge, Louisiana.
- Researchers are still unsure whether or not obesity will affect vaccine efficacy. And there might be ways to counteract problems if they arise. But scientists are also concerned that clinical trials might not be well designed to capture such issues promptly. “It‘s something the experts need to really look at,” says Ryan.
- It was clear early in the outbreak that obesity heightened the risk for people infected with the coronavirus. When epidemiologist Lin Xu at Sun Yat-Sen University in Guangzhou, China, was analysing data from the earliest wave of the epidemic in China, she noticed a pattern emerging in model after model. “BMI was always there,” she says. “It is always positively associated with severity of C19.”
- When Xu submitted her study to an academic journal in March, the editors urged her to alert the World Health Organization about her findings. Since then, studies have poured in from countries around the world reaching the same conclusion: those who are obese are more likely to die from C19 than are those of normal weight, even when factors such as diabetes and hypertension are taken into account.
- There are a slew of possible reasons. People with higher BMIs are more difficult to care for. It can be challenging to put a tube down their airway when hooking them up to a ventilator, for example. They can also have reduced lung capacity.
- Then there are the more-hidden, molecular possibilities. Insulin resistance makes it difficult for the body to respond normally to sugar and can precede diabetes. It is more common in those with high BMIs and could exacerbate the metabolic effects of coronavirus infection. And adipose tissue expresses relatively high levels of the ACE2 (angiotensin-converting enzyme 2) receptor that the coronavirus(SARS-CoV-2) uses to gain entry into cells. “Adipose tissue seems to work like a reservoir of the virus,” says Gianluca Iacobellis, an endocrinologist at the University of Miami in Florida.
- But the effects on the immune system are what concern some researchers the most. Obesity can cause chronic, low-grade inflammation, which is thought to contribute to the increased risk of conditions such as diabetes and heart disease. As a result, people who are obese might have higher levels of a variety of immune-regulating proteins, including cytokines. The immune responses unleashed by cytokines can damage healthy tissue in some cases of severe C19, says Milena Sokolowska, who studies immunology and respiratory diseases at the University of Zurich in Switzerland. And the constant state of immune stimulation can, paradoxically, weaken some immune responses, including those launched by T cells, which can directly kill infected cells. “I would say they are more exhausted at the start in their fight with infection,” says Sokolowska.
- Preliminary evidence suggests that SARS-CoV-2 infections linger for about five days longer in people who are obese than in those who are lean, says endocrinologist Daniel Drucker of the Mount Sinai Hospital in Toronto, Canada. “That would imply that these people are having trouble clearing the infection,” he says. “They may have trouble mounting normal viral defenses.”
- Obesity is also linked to less-diverse populations of microbes in the gut, nose and lung, with altered compositions and metabolic functions compared with those in lean individuals. Gut microbes can influence the immune responses to pathogens — and to vaccines, says Sokolowska. Last year, for example, researchers reported that the changes to the gut microbiome that come with taking antibiotics alter responses to a flu vaccine.
- All this could spell trouble for a SARS-CoV-2 vaccine, when it arrives, particularly in the growing list of countries with obesity problems. According to the latest data from the World Health Organization, about 13% of the world’s adults are obese. Ryan points to studies of vaccines against influenza, hepatitis B and rabies, which have shown reduced responses in those who are obese compared with those who are lean. “With influenza, we’re seeing that vaccination does not work well in those who are obese,” says Xu. “We don’t have the data yet on coronavirus.”
- Some are unconvinced that obesity will blunt the efficacy of vaccines. Drucker notes that the studies on influenza vaccines were relatively small. “It’s certainly a reasonable hypothesis,” he says. “But I don’t think that we can look at influenza as a clear example.”
Forewarned is forearmed
- There might be ways to compensate for vaccine shortcomings, just as researchers have been working to improve vaccine response in elderly people. Giving obese people extra doses of vaccine is one possibility, says Ryan. “Maybe three injections instead of two, maybe a larger dose — we shouldn’t just throw up our hands and say it’s not going to work.”
- There are three leading candidate vaccines currently being tested in large clinical trials. This could offer a chance to evaluate how well they work, not only in the population at large, but in obese individuals in particular, says Barry Popkin,who studies nutrition at the University of North Carolina in Chapel Hill. But it’s unclear whether, or when, the studies will have sufficient power to discern a difference between obese and lean individuals, he says.
- A trial being run by biotechnology firm Moderna in Cambridge, Massachusetts, aims to enroll 30,000 participants, but is planning to base its conclusions on data from the first 151 people who go on to develop a C19 infection. Other large vaccine trials have set similar targets. Depending on what countries the participants hail from, the trial might not have a sample that will allow it to determine whether obesity affects the vaccine response. “It depends on who volunteers,” says Popkin.
- It might also depend on how well trial sponsors recruit individuals from under-represented minority groups, which have been hard hit by the C19 pandemic and also experience high rates of obesity, says vaccinologist Gregory Poland at Mayo Clinic in Rochester, Minnesota.
- Poland says that he has urged pharmaceutical companies to stratify their data by BMI, but he worries that the word is not getting out. “I will not be surprised if antibody levels are lower and don’t last as long in people who are obese or overweight,” he says. “It won’t be a surprise to some of us, but it will be a shock to the rest.”
- Even if antibody responses seem robust, that could be misleading, cautions Melinda Beck, who studies the relationship between nutrition and immune responses at the University of North Carolina. In her studies, she says, obese people have normal initial antibody levels in response to flu vaccines, but are still twice as likely as vaccinated lean people to get the flu (that’s not to say that vaccination offers obese people no benefit). And analyses so far have focused on Western definitions of obesity. These are based on BMI, a crude measure that fails to distinguish between fat that accumulates under the skin, and fat that accumulates around organs, called visceral fat, which is more closely associated with diseases such as diabetes and high blood pressure.
- In people of European descent, a BMI of 30 kilograms per square metre or above is considered obese. But Popkin notes that people in some countries in Asia, the Middle East and Latin America, for example, tend to accumulate visceral fat at lower BMIs. China is the only country to set a lower threshold — a BMI of 28 kg m–2 — for obesity, but even then, Popkin says, some Chinese researchers will report their data using Western definitions of BMI to improve their chances of publishing.
- Ultimately, the world will probably need to wait for data from clinical studies to show the way, says Drucker. But the waiting could be nerve-wracking. Sosa-García and others hope that the association between C19 and obesity will force some governments and health-care systems to engage with the growing obesity problems in their countries. “If you are a public-health official and you’re looking at 40% of your population at high risk, that data is saying, ‘wake up and take notice’.”
2. How anti-ageing drugs could boost COVID vaccines in older people
- Unlike fine wine, the human body does not improve with age. Hearing fades, skin sags, joints give out. Even the body’s immune system loses some of its vigor.
- This phenomenon, known as immunosenescence, might explain why older age groups are so hard-hit by C19. And there is another troubling implication: vaccines, which incite the immune system to fight off invaders, often perform poorly in older people. The best strategy for quelling the pandemic might fail in exactly the group that needs it most.
- Scientists have known for decades that ageing immune systems can leave the body prone to infection and weaken their response to vaccines. In June, the FDA announced that a C19 vaccine would have to protect at least half the vaccinated individuals to be considered effective, but protection in older adults might not even meet that bar. “No vaccine is going to be as effective in the elderly as it is in young people,” says Matt Kaeberlein, a gerontologist at the University of Washington in Seattle. “That’s an almost certainty.”
- The human immune system is mind-bendingly complex, and ageing affects nearly every component. Some types of immune cell become depleted: for example, older adults have fewer naive T cells that respond to new invaders, and fewer B cells, which produce antibodies that latch on to invading pathogens and target them for destruction. Older people also tend to experience chronic, low-grade inflammation, a phenomenon known as inflammageing (see ‘Depleted defenses’). Although some inflammation is a key part of a healthy immune response, this constant buzz of internal activation makes the immune system less responsive to external insults. “This overarching, chronic inflammatory state is what’s driving much of the immune dysfunction that we see,” says Kaeberlein. The upshot is a poorer reaction to infections and a dulled response to vaccines, which work by priming the immune system to fight off a pathogen without actually causing disease.
- With about 50 C19 vaccine candidates currently being tested in humans, researchers say it’s not yet clear how they will fare in older adults. In its phase I study of 40 people aged 56 and over, Moderna in Cambridge, Massachusetts, reported that its candidate mRNA-1273 elicited similar antibody levels as those elicited in a younger age group. The Chinese biotech Sinovac in Beijing, which trialled its CoronaVac candidate in a phase I/II study that included 421 adults between 60 and 89 years of age, announced in a press release on 9 September that it seems to work as well in older adults as it does in younger ones. However, a phase I study by international pharma company Pfizer and BioNTech in Mainz, Germany, showed that their vaccine BNT162b2 provokes an immune response that is about half as strong in older adults as it is in younger ones. The older adults still produced more antibodies in response to the vaccine than people of a similar age who had had C19, but it’s not known how these levels translate into protection from the virus.
- Most C19 vaccine trials include at least some older adults. But a recent analysis of 18 such trials found that the risk of exclusion is high. More than half had age cut-offs and many were at risk of excluding older participants for other reasons, including underlying conditions.
- If C19 vaccines perform less well in older adults, researchers might be able to find ways to tweak the shot itself to elicit a stronger response. Some influenza vaccines, for instance, include immune-boosting ingredients or higher doses of the viral antigen. But some scientists say there is a better option. They are developing and testing drugs that could improve how older adults respond to vaccines and might also help them fight viruses more effectively in the first place. Rather than working with the limitations of the ageing immune system, they are planning to rejuvenate it.
- Many researchers have grown old trying to pinpoint ways to reverse the ageing process. In the past decade, however, they have made serious progress in identifying particular molecular targets that might help in this quest.
- One promising class of anti-ageing drug acts on pathways involved in cell growth. These drugs inhibit a protein known as mTOR. In the laboratory, inhibiting mTOR lengthens lifespan in animals from fruit flies to mice. “mTOR is one of probably multiple biologic mechanisms that contribute to why we age and why our organ systems start to decline,” says Joan Mannick, co-founder and chief medical officer of resTORbio, a biotech company based in Boston, Massachusetts, that aims to develop anti-ageing therapies.
- In a study published in 2018 and carried out when Mannick was at the Novartis Research Institutes in Cambridge, Massachusetts, she and her colleagues tried damping down mTOR in elderly adults to see if this could improve immune function and lower infection rates. The 264 participants received a low-dose mTOR inhibitor or a placebo for six weeks. Those who received the drug had fewer infections in the year after the study and an improved response to the flu vaccine. On the basis of her work on mTOR inhibition, Mannick, by then at resTORbio, launched a phase III trial in 2019 to see if a similar mTOR inhibitor called RTB101 could stave off respiratory illnesses in older adults.
- That trial failed to show the desired effect, perhaps because infections were monitored by self-report of symptoms rather than requiring a lab test to confirm infection, as in the earlier trial. That created “a lot more noise”, says Ilaria Bellantuono, co-director of the Healthy Lifespan Institute at the University of Sheffield, UK, who was not involved in the trial. “A much bigger group would have been required to see a difference.”
- Still, the data from this and an earlier trial suggested that participants who received the mTOR inhibitor had fewer severe infections from circulating coronaviruses and recovered faster from them than the placebo group. The trials pre-date the emergence of the coronavirus (SARS-CoV-2), but they suggest that RTB101 could lessen the severity of infection. resTORbio is now testing that idea in 550 nursing-home residents aged 65 and over.
- RTB101 is similar to an already approved mTOR inhibitor, the immune-suppressing drug rapamycin. At least four other groups are testing rapamycin in small numbers of infected individuals as a possible C19 therapy; one group is trialling the drug exclusively in adults aged 60 or older.
Genetic secrets of the healthy elderly revealed
- The type 2 diabetes drug metformin also dampens down mTOR’s activity, albeit indirectly. Some studies suggest that people who take metformin are less likely to be hospitalized or die if they contract C19. A small retrospective study in China found that the mortality among hospitalized individuals with C19 taking metformin was 2.9% compared with 12.3% in people who didn’t take the drug. Researchers at the University of Minnesota in Minneapolis analyzed data on hospitalized individuals with C19 who had an average age of 75, some of whom were already taking metformin for obesity or diabetes. They found a significant reduction in mortality among women taking metformin, but not among men.
- Carolyn Bramante, an obesity researcher who led the University of Minnesota study, points out that diseases such as diabetes and obesity lead to some of the same immune deficits as occur in older age. She and her colleagues plan to launch a trial of 1,500 people aged 30 and over to determine whether metformin could help stave off SARS-CoV-2 infection or prevent the worst outcomes in people already infected.
- Meanwhile, Jenna Bartley, who studies ageing at the University of Connecticut in Storrs, is assessing whether metformin can boost responses to flu vaccine in a small trial of older adults. The idea, based on her work in mice, is that metformin can improve the energy metabolism of the T cells of the immune system, making them better at detecting new threats. Bartley has finished collecting data, but because her lab was shut down owing to C19, she won’t have the results analysed for a few more weeks.
- If metformin works against C19, researchers will still have to tease out why. Kaeberlein points out that no one is quite sure how metformin works because it has so many targets. “It’s about the dirtiest of dirty drugs out there,” he says. It was originally used as an anti-influenza drug; Bramante says it helps tamp down inflammation. Aside from the mechanistic unknowns, the advantage is that metformin has been used for decades and is generally safe. Children can take it, as can pregnant women. “Metformin is a medication that you actually could give prophylactically for 12 months without having to do any follow-up,” Bramante says, “and it costs less than US$4 a month.”
- mTOR is a classic anti-ageing target, but it’s far from the only one. In fact, many anti-ageing pathways seem to be linked, says James Kirkland, who studies cellular ageing and disease at the Mayo Clinic in Rochester, Minnesota. “That is, if you target one, you tend to affect all the rest,” he says. Many of the immune changes that come with ageing lead to the same result: inflammation. So researchers are looking at drugs that will calm this symptom.
- Arne Akbar, an immunologist at University College London, has shown that the anti-inflammatory drug losmapimod, which is being developed as a therapy for muscular dystrophy, might help boost immunity. In a 2018 study, the researchers injected chickenpox virus into the skin of elderly adults. Although these people had already been exposed to chickenpox, their immune response was lacklustre, hampered by excess inflammation. When the team gave the study participants losmapimod, it ratcheted down inflammation by about 70% and improved their immune responses.
- In June, the company currently developing losmapimod — Fulcrum Therapeutics in Cambridge, Massachusetts — launched a 400-person phase III study to investigate whether the drug could prevent death and respiratory failure in older people hospitalized with C19.
- Another class of drug, called senolytics, helps to purge the body of cells that have stopped dividing but won’t die. These senescent cells are typically cleared by the immune system, but as the body ages, they begin to accumulate, ramping up inflammation. In August, Kirkland and a team at the Mayo Clinic launched a 70-person trial to test whether a senolytic called fisetin, which is found in strawberries and sold as a health supplement, can curb progression of C19 in adults aged 60 or older. They also plan to test whether fisetin can prevent C19 infection in nursing-home residents.
- “Senescence is really a key factor in ageing,” says Eric Verdin, president and chief executive of the Buck Institute for Research on Aging in Novato, California, who is not involved in the fisetin research. No senolytics have currently been approved for clinical treatment, however. “This is one area that has been much less studied,” he says.
- Kaeberlein says it’s likely that most companies will pursue anti-ageing drugs as therapies before they test them as prophylactics. “It’s much easier to get a therapy approved in people who are already sick,” he says. He thinks that mTOR inhibitors hold the most promise. “If I had the power to go back to the beginning of this whole COVID pandemic and try one thing, I’d pick mTOR inhibitors — rapamycin specifically,” he says. According to his back-of-the-envelope calculations, if rapamycin works in the same way in people as it does in mice, it could reduce C19 mortality by 90%.
- Kirkland says he can envisage giving one of these anti-ageing drugs as a primer before vaccination. “We have to figure out ways to target fundamental ageing mechanisms at around the time that we’re vaccinating people,” he says, “but we have to find ways of doing this that are safe and effective.”
- If tweaking the immune system proves too challenging, there might be ways to juice up the vaccine itself. For flu, there are two vaccines aimed specifically at people over 65, which help worn immune systems to stage a response. One, Fluzone High-Dose, contains four times the standard amount of flu virus antigens, and the other, Fluad, relies on an immune-boosting molecule called an adjuvant.
- A team led by vaccinologist Ofer Levy at Boston Children’s Hospital in Massachusetts is working on a C19 vaccine specifically for older adults, using an in-vitro screening system to identify the best adjuvants. “Vaccines were typically developed as one-size-fits-all,” he says. But a lot of features — age, sex, and even the season — affect vaccine responses, Levy says. The best combinations of adjuvant and vaccine they find will be tested in mice and then in humans.
- But, in general, developing medications to improve immune function seems like a much smarter strategy than creating vaccines specifically for elderly people, says Claire Chougnet, an immunologist at Cincinnati Children’s Hospital Medical Center in Ohio, who is studying inflammation in aged mice. Vaccine development is costly and time-intensive. “In the case of an emerging virus, when you want a quick response, that makes things even more complicated if you have to do two types of vaccine,” she says. Plus, individual vaccines target specific pathogens, but an immune-boosting medication could be used with any vaccine. “That could work for flu, that could work for C19. That would work for COVID-25,” she says. The approach is “extremely versatile”.
- Verdin agrees that supporting the older immune system should be a priority. “I think the net result of all this will be renewed interest in understanding the defect in the immune response in the elderly.” That has implications not only for the coronavirus, but also for a host of other diseases, including other viral infections and even cancer. “C19 has brought to the front something that a lot of people have ignored.”
3. If you’re pinning your hopes on a Covid vaccine, here’s a dose of realism
- For those holding on to hope of an imminent C19 vaccine, the news this weekend that the first could be rolled out as early as “just after Christmas” will have likely lifted the spirits.
- The UK’s deputy chief medical officer, Prof Jonathan Van-Tam, reportedly told MPs a vaccine developed by Oxford University and AstraZeneca could be ready for deployment in January, while Sir Jeremy Farrar, Sage scientific advisory group member and a director of the Wellcome Trust, has said at least one of a portfolio of UK vaccines could be ready by spring.
- Much has been said about how the world will return to normal when a vaccine is widely available. But that really won’t be true. It is important that we are realistic about what vaccines can and can’t do.
- Vaccines protect individuals against disease and hopefully also against infection, but no vaccine is 100% effective. To know what proportion of a community would be immune after a vaccination programme is a numbers game – we must multiply the proportion of a population vaccinated by how effective the vaccine is.
- The UK currently has among the highest national coverage of flu vaccine in the world, vaccinating around 75% of the over-65s against flu every year; most countries either do worse or have no vaccination programmes for older people. It is reasonable to expect that this level of coverage could be achieved for a C19 vaccine in that age group in the UK.
- Therefore, if the C19 vaccine is 75% effective – meaning that 75% of those vaccinated become immune – then we would actually only protect 56% of that target population (75% of 75%). This would not be enough to stop the virus circulating. Almost half of our highest risk group would remain susceptible, and we won’t know who they are. Relaxing social distancing rules when facing those risks seems a bit like Russian roulette.
- Now let’s look at people younger than 65 in medical risk groups. In a good year, the UK vaccinates 50% of them against the flu. That means just over a 33% of them are going to be protected (50% of 75%). Just to make matters worse, regulators such as the US Food and Drug Administration and the European Medicines Agency have said that they would accept a 50% lower level for efficacy for candidate C19 vaccines. If that efficacy level is fulfilled, we have to multiply coverage by 50% efficacy, not 75%, and suddenly it all gets more concerning.
- As well as protecting individuals, vaccines can protect communities, through the interruption of transmission. One of the best examples comes from the UK meningitis C vaccination campaign of the late 1990s. There was a 67% reduction in the number of cases in unvaccinated children and young people because they were being protected by their contacts who had been vaccinated and were no longer transmitting infection.
- If we want to see population protection from a C19 vaccination, we are going to need high levels of protection (coverage x efficacy) across all ages – vaccinating not just the at-risk groups, as is being planned.
- To stop transmission, we must vaccinate anyone who can transmit infection. Anything less means that our goal is only individual protection and not the interruption of transmission. A recent announcement from the head of the UK vaccine taskforce, that the strategy will be targeted vaccination, makes it abundantly clear that the UK vaccine strategy at the moment is not to try to interrupt transmission, despite having hundreds of millions of C19 vaccine doses on contract. With less than 10% of the population showing evidence of having been infected, targeted vaccination will not allow “life as previously usual” to return.
- Even if countries do decide to switch from a personal-protection policy to a transmission-interruption strategy, obstacles remain. Much will depend on the successful vaccination (probably with two doses) of people who have not previously seen themselves to be at elevated risk. The challenge will be persuading the young, for example, to be vaccinated, not for their own benefit, but for the benefit of others.
- Adherence to recommendations for any C19 interventions – social distancing, lockdowns, home working, cancelled holidays or vaccinations – depend on trust. If politicians are telling us that the present impositions on our lives are only going to last until we have vaccines, then the reality is that a false hope is being promulgated.
- Vaccines are probably the most powerful public health intervention available to us. But unless their benefits are communicated with realism, confidence in all recommendations will be put at risk.
- While hope and optimism are much needed in these dark times, it is important to be transparent. We need to communicate the clear message that although targeted vaccination may offer some protection, it will not simply deliver “life as we used to know it”.
4. C19 vaccine trials cannot tell us if they will save lives
- Vaccines are being hailed as the solution to the C19 pandemic, but the vaccine trials currently underway are not designed to tell us if they will save lives, reports Peter Doshi, Associate Editor at The BMJ today.
- Several C19 vaccine trials are now in their most advanced (phase 3) stage, but what will it mean exactly when a vaccine is declared “effective”?
- Many may assume that successful phase 3 studies will mean we have a proven way of keeping people from getting very sick and dying from C19. And a robust way to interrupt viral transmission.
- Yet the current phase 3 trials are not actually set up to prove either, says Doshi.
- “None of the trials currently underway are designed to detect a reduction in any serious outcome such as hospitalizations, intensive care use, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus,” he writes.
- He explains that all ongoing phase 3 trials for which details have been released are evaluating mild, not severe, disease – and they will be able to report final results once around 150 participants develop symptoms.
- In Pfizer and Moderna’s trials, for example, individuals with only a cough and positive lab test would bring those trials one event closer to their completion.
- Yet Doshi argues that vaccine manufacturers have done little to dispel the notion that severe C19 was what was being assessed.
- Moderna, for example, called hospitalizations a “key secondary endpoint” in statements to the media. But Tal Zaks, Chief Medical Officer at Moderna, told The BMJ that their trial lacks adequate statistical power to assess that endpoint.
- Part of the reason may be numbers, says Doshi. Because most people with symptomatic C19 infections experience only mild symptoms, even trials involving 30,000 or more patients would turn up relatively few cases of severe disease.
- “Hospitalizations and deaths from C19 are simply too uncommon in the population being studied for an effective vaccine to demonstrate statistically significant differences in a trial of 30,000 people,” he adds. “The same is true regarding whether it can save lives or prevent transmission: the trials are not designed to find out.”
- Zaks confirms that Moderna’s trial will not demonstrate prevention of hospitalization because the size and duration of the trial would need to be vastly increased to collect the necessary data. “Neither of these I think are acceptable in the current public need for knowing expeditiously that a vaccine works,” he told The BMJ.
- Moderna’s trial is designed to find out if the vaccine can prevent C19 disease, says Zaks. Like Pfizer and Johnson and Johnson, Moderna has designed its study to detect a relative risk reduction of at least 30% in participants developing lab-confirmed C19, consistent with FDA and international guidance.
- Zaks also points to influenza vaccines, saying they protect against severe disease better than mild disease. “To Moderna, it’s the same for C19: if their vaccine is shown to reduce symptomatic C19, they will feel confident it also protects against serious outcomes,” Doshi writes.
- But Doshi raises another important issue – that few or perhaps none of the current vaccine trials appear to be designed to find out whether there is a benefit in the elderly, despite their obvious vulnerability to C19.
- If the frail elderly are not enrolled into vaccine trials in sufficient numbers to determine whether there is a reduction in cases in this population, “there can be little basis for assuming any benefit against hospitalization or mortality,” he warns.
- Doshi says that we still have time to advocate for changes to ensure the ongoing trials address the questions that most need answering.
- For example, why children, immunocompromised people, and pregnant women have largely been excluded; whether the right primary endpoint has been chosen; whether safety is being adequately evaluated; and whether gaps in our understanding of how our immune system responds to C19 are being addressed.
- “The C19 vaccine trials may not have been designed with our input, but it is not too late to have our say and adjust their course. With stakes this high, we need all eyes on deck,” he argues.
5. Dozens to be deliberately infected with coronavirus in UK ‘human challenge’ trials
- Young, healthy people will be intentionally exposed to the virus responsible for C19 in a first-of-its-kind ‘human challenge trial’, the UK government and a company that runs such studies announced on 20 October. The experiment, set to begin in January in a London hospital if it receives final regulatory and ethical approval, aims to accelerate the development of vaccines that could end the pandemic.
- Human challenge trials have a history of providing insight into diseases such as malaria and influenza. The UK trial will try to identify a suitable dose of the SARS-CoV-2 virus that could be used in future vaccine trials. But the prospect of deliberately infecting people — even those at low risk of severe disease — with SARS-CoV-2, a deadly pathogen that has few proven treatments, is uncharted medical and bioethical territory.
- Proponents of C19 challenge trials have argued that they can be run safely and ethically, and that their potential to quickly identify effective vaccines outweighs the low risks to participants. But others have raised questions about the safety and value of these studies, pointing out that large-scale efficacy trials involving tens of thousands of people are expected to deliver results on several C19 vaccines soon.
- “Deliberately infecting volunteers with a known human pathogen is never undertaken lightly. However, such studies are enormously informative about a disease,” Peter Openshaw, an immunologist at Imperial College London and investigator on the study, said in a press statement. “It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for C19, and challenge studies have the potential to accelerate and de-risk the development of novel drugs and vaccines.
- The planned C19 challenge study will be led by a Dublin-based commercial clinical-research organization called Open Orphan and its subsidiary hVIVO, which runs challenge trials on respiratory pathogens. It will take place in the high-level isolation unit of the Royal Free Hospital in north London, says Open Orphan executive chair Cathal Friel.
- The initial trial will involve an estimated 30 to 50 participants, says Andrew Catchpole, a virologist and the chief scientific officer at Open Orphan who is leading the work. It is open only to healthy adults aged 18 to 30.
- The precise design of the study has not been finalized. But it is likely that a small number of participants will receive a very low dose of a SARS-CoV-2 ‘challenge strain’ derived from a currently circulating virus and grown under stringent conditions. If none or few of the participants become infected, the researchers will seek permission from an independent safety monitoring board to expose participants to higher doses. This process will be repeated until researchers identify a dose that infects most of those exposed, says Catchpole.
- Once an appropriate dose is identified, Open Orphan could be asked to run a series of challenge trials testing several vaccines. Catchpole says that the design of these trials, including which vaccines will be included, has not been determined. He envisions that some trial participants will receive a placebo injection instead of a vaccine, but he also says that head-to-head trials comparing two or more vaccines could be run. Other vaccine studies that the company runs typically enrol 40–50 volunteers for each trial arm, he says.
- Catchpole says that his team will take every precaution against participants in the initial trial developing severe disease. Volunteers will be treated with an antiviral, such as remdesevir, once a nasal swab gives a positive result for SARS-CoV-2 genetic material. In addition to age and health, participants will be screened for risk factors that have been associated with severe C19.
- Selecting participants at the lowest risk is the most important safety step in running a challenge trial, says Matt Memoli, an infectious-disease physician and virologist at the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. “Once you’ve given that virus to the person, anything’s possible,” he says. “You can’t control it, you can only react to it.”
- If Open Orphan moves on to vaccine trials, it will aim to recruit around 500 participants altogether, but Friel says the company will need to screen many times more people to identify suitable volunteers. An ethical review board will determine how to compensate participants. Open Orphan typically pays volunteers around £4,000 for their time, says Catchpole.
E. Improved & Potential Treatments
1. Mouthwash May Inactivate Coronavirus, Help Reduce Spread of C19
- Certain oral antiseptics and mouthwashes may have the ability to inactivate human coronaviruses, according to a Penn State College of Medicine research study. The results indicate that some of these products might be useful for reducing the viral load, or amount of virus, in the mouth after infection and may help to reduce the spread of the coronavirus (SARS-CoV-2).
- Craig Meyers, distinguished professor of microbiology and immunology and obstetrics and gynecology, led a group of physicians and scientists who tested several oral and nasopharyngeal rinses in a laboratory setting for their ability to inactivate human coronaviruses, which are similar in structure to SARS-CoV-2. The products evaluated include a 1% solution of baby shampoo, a neti pot, peroxide sore-mouth cleansers, and mouthwashes.
- The researchers found that several of the nasal and oral rinses had a strong ability to neutralize human coronavirus, which suggests that these products may have the potential to reduce the amount of virus spread by people who are C19-positive.
- “While we wait for a vaccine to be developed, methods to reduce transmission are needed,” Meyers said. “The products we tested are readily available and often already part of people’s daily routines.”
- Meyers and colleagues used a test to replicate the interaction of the virus in the nasal and oral cavities with the rinses and mouthwashes. Nasal and oral cavities are major points of entry and transmission for human coronaviruses.
- They treated solutions containing a strain of human coronavirus, which served as a readily available and genetically similar alternative for SARS-CoV-2, with the baby shampoo solutions, various peroxide antiseptic rinses and various brands of mouthwash. They allowed the solutions to interact with the virus for 30 seconds, one minute and two minutes, before diluting the solutions to prevent further virus inactivation. According to Meyers, the outer envelopes of the human coronavirus tested and SARS-CoV-2 are genetically similar so the research team hypothesizes that a similar amount of SARS-CoV-2 may be inactivated upon exposure to the solution.
- To measure how much virus was inactivated, the researchers placed the diluted solutions in contact with cultured human cells. They counted how many cells remained alive after a few days of exposure to the viral solution and used that number to calculate the amount of human coronavirus that was inactivated as a result of exposure to the mouthwash or oral rinse that was tested. The results were published in the Journal of Medical Virology.
- The 1% baby shampoo solution, which is often used by head and neck doctors to rinse the sinuses, inactivated greater than 99.9% of human coronavirus after a two-minute contact time.
- Several of the mouthwash and gargle products also were effective at inactivating the infectious virus. Many inactivated greater than 99.9% of virus after only 30 seconds of contact time and some inactivated 99.99% of the virus after 30 seconds.
- According to Meyers, the results with mouthwashes are promising and add to the findings of a study showing that certain types of oral rinses could inactivate SARS-CoV-2 in similar experimental conditions. In addition to evaluating the solutions at longer contact times, they studied over-the-counter products and nasal rinses that were not evaluated in the other study. Meyers said the next step to expand upon these results is to design and conduct clinical trials that evaluate whether products like mouthwashes can effectively reduce viral load in C19-positive patients.
- “People who test positive for C19 and return home to quarantine may possibly transmit the virus to those they live with,” said Meyers, a researcher at Penn State Cancer Institute. “Certain professions including dentists and other health care workers are at a constant risk of exposure. Clinical trials are needed to determine if these products can reduce the amount of virus COVID-positive patients or those with high-risk occupations may spread while talking, coughing or sneezing. Even if the use of these solutions could reduce transmission by 50%, it would have a major impact.”
- Future studies may include a continued investigation of products that inactive human coronaviruses and what specific ingredients in the solutions tested inactivate the virus.
2. Arthritis drug tocilizumab shown effective for sickest C19 patients
- In a large clinical study, tocilizumab, an immune modulator long used to treat rheumatoid arthritis, showed it can save lives if given to critically ill C19 patients within the first two days of being admitted to an intensive care unit.
- The study, published in JAMA Internal Medicine, showed just over 27% of ICU patients treated with tocilizumab died within a month, compared with 37% of those just as seriously ill but did not receive the drug.
- Tocilizumab, a so-called monoclonal antibody, has been used during the outbreak because of its effect on tamping down immune over-reactions, which have been common with C19. Smaller studies, including one published at the same time by the same journal have shown mixed results, with some finding the drug did not reduce deaths.
- Dr. David Leaf, the senior author on the new paper, said that’s why it’s so important during the pandemic to have large, randomized trials comparing a drug option against a placebo, especially among the sickest patients.
- Most randomized studies conducted so far in C19 haven’t been large enough or included enough very ill patients to know whether a drug can improve survival, he said.
- “They’re just not anywhere close to being adequately powered to assess mortality,” he said.
- Leaf, a kidney specialist at Brigham and Women’s Hospital and Harvard Medical School, collaborated with researchers at 67 other hospitals across the U.S. to conduct their new study, tracking 4,000 critically ill patients early in the pandemic. The group has already published several studies, including one showing heart attacks are very common among critically ill C19 patients, and tend to lead to poor outcomes, even in those who receive CPR. Future research will look at other treatments for very ill patients, he said.
- Leaf said his study reinforces the idea that different drugs should be used at different times during C19 treatment. Tocilizumab appeared to be particularly helpful for patients admitted to an ICU within three days of developing symptoms, he said.
- “If you wait too long, you’re waiting for irreversible organ injury to have occurred,” he said, and the drug may no longer be effective.
- About 20% of the ICU patients examined had symptoms for just a few days before landing in intensive care, he said. For that subset of patients, unlike any other, tocilizumab appears to offer a substantial survival benefit.
- Many patients with serious C19 cases, like President Donald Trump, receive steroids to tamp down an immune overreaction. Leaf compared steroids to a sledgehammer, acting on the entire immune system, while tocilizumab is a scalpel, targeting a particular immune molecule called IL-6.
- Tocilizumab is usually given to C19 patients just once, through an intravenous injection. A second dose can be given if needed several days later.
F. Concerns & Unknowns
1. Kidney disease tied to high death rates in COVID patients
- C19 patients who have chronic kidney disease (CKD) or develop coronavirus-related kidney injury in the intensive care unit (ICU) face higher odds of death than their otherwise-healthy peers, according to a study published late last week in Anaesthesia.
- Led by researchers at Imperial College London, the retrospective study involved 372 adult C19 patients in four ICUs in the United Kingdom from Mar 10 to Jul 31. Of the 372 patients, 216 (58%) had kidney impairment, 22% of which was CKD (48 patients) and 78% of which developed during hospitalization (168 patients).
Degree of injury, need for dialysis
- In total, 139 of 372 patients (37%) died. Of the 156 patients with healthy kidneys, 32 (21%) died in the hospital, in contrast with 81 of 168 patients (48%) with newly developed kidney injury and 11 of 22 (50%) with CKD stage 1 through 4.
- Among the other 26 patients who had CKD, 9 of 19 patients (47%) with end-stage renal failure (ESRF), who had already required routine outpatient dialysis, died. The death rate was highest in CKD patients who had undergone kidney transplant (6 of 7 [86%]).
- Death rates rose along with worsening kidney injury classified by Kidney Disease: Improving Global Outcomes (KDIGO) classification; of 157 patients with stage 0 (least) injury, 33 (21%) died, compared with those with more serious stages 1 to 3 injury (91/186 [49%]).
- Those who died were more likely to have needed dialysis than survivors (64/139 [46%] vs 57/233 [24%]). But once dialysis was started, death rates were not significantly different between survivors and non-survivors in patients with new kidney injury (39/82 [48%] vs 43/82 [52%]) or non–end-stage CKD (8/17 [47%] vs 9/17 [53%]).
- Among 216 patients with kidney impairment, 121 (56%) needed dialysis in the hospital, and 9 of the 48 survivors who required dialysis for the first time in the ICU (19%) continued to need it after they were released, suggesting that C19 may lead to long-term kidney impairment. Most patients (337 of 372 [91%] required mechanical ventilation. Median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15, with 0 the least likely to die in the ICU and 71 the most likely.
Vigilance, intensive care
- The authors said that were surprised that the death rate in patients with ESRF and on dialysis, who usually have poorer outcomes in many other illnesses, wasn’t significantly higher than in those with less-serious CKD and coronavirus-related kidney injury. The finding, they noted, suggests that C19 patients receiving dialysis—including those with ESRF—have a similar chance for survival as those with less severe disease or injury and thus should be considered for ICU care.
- But the researchers caution that their results may have been subject to selection bias, in which some patients with ESRF who were too sick for admission to the ICU may not have been included in the study during the peak of the last UK C19 surge.
- Patients were, on average, about 60 years old, 72% of them were men, and 76% were black or Asian.
- The authors said that they don’t know exactly why patients with impaired kidneys are more likely than others to die of C19 but theorize that it could be because the virus causes inflammation of the kidney blood vessels, similar to how it inflames the lungs; the enhanced immune response (“cytokine storm”) triggered by the virus injures the kidneys; or multiorgan failure leads to kidney tissue death.
- “Our data demonstrate that renal impairment in patients admitted to intensive care with C19 is common and is associated with a high mortality and requirement for on‐going renal support after discharge from critical care,” the authors wrote. “Attention needs to be paid to patients with C19 with any form of renal impairment and every effort made to prevent progression of renal injury in order to reduce mortality.”
- The researchers also remarked that patients who require dialysis in the hospital have a much lower survival rate than those who don’t, which could have implications for resource allocation. “The impact on resource utilisation is considerable, especially in a pandemic situation where resources may have to be rationed,” they wrote.
2. Does America Have A COVID Problem Or An Obesity Problem?
- While we have previously reported – and by now it is common knowledge – that C19 usually kills only the very old with virtually no deaths in the 45 and under category and most deaths in the 75 and over category.
- Indeed, as Deutsche Bank’s Jim Reid noted when discussing the average age of fatalities from Covid, “it is remarkably consistent around the 80-82 year old mark.”
- Then overnight, Bloomberg’s John Authers pointed out how startling this mortality rate varies from country to country, when referencing another chart from Jim Reid:
- As Authers writes, “The U.S. is a remarkable outlier. How can that possibly be?”
- According to Reid, a small part of this might be down to many of the other countries having an older population. For example, Italy’s median age is 45 (43 in Europe), whereas it is 38 for the US.
- However, another explanation offered by the Bloomberg commentator, which feeds into the political debate of the moment, “is that all the other developed countries on this chart have some form of universal state-provided healthcare.” But rather than get embroiled in that debate, Authers instead looks at the normal average age of people when they die. The following is a chart of life expectancy (in years) at birth for all the members of the Organization for Economic Cooperation and Development:
- As shown in the chart above, the U.S. – which as we discussed last week is turning into a banana republic with just a 50% share of the population in middle-income households, roughly the same category as Turkey, China and, drumroll, Russia – has lower life expectancy than the Czech Republic or Chile, and is lagged only by countries that are significantly poorer. It trails the other major economies by several years, in many cases roughly equal to the gap in the age at which C19 victims die.
- According to Authers, instead of focusing on Covid, “it might make sense for the U.S. healthcare debate to revolve around treating this as a national disgrace and trying to make common cause over fixing it, rather than having an arid political argument, but I digress.”
- Which brings us to the topic at hand, namely does America have a covid problem, or is it just an extension of America’s far more serious problem of obesity. To wit, one of its greatest life-shortening effects is diabetes. Here are the most recent OECD numbers on diabetes prevalence:
- As Authers observes, “the U.S. lags behind only the much poorer nations of Turkey and Mexico in this dismal category, and has more than double the diabetes prevalence of the main developed economies of Europe”, and summarizes:
- Once the country has finished tearing itself apart over the pandemic, which will probably only happen once the virus has finally gone away, a new debate over diabetes and obesity will be necessary. Let’s hope it can be more constructive than the current one.
- The numbers also shed light on why the US has had a relatively difficult time containing the pandemic according to the Bloomberg author, and also suggests that a “Swedish” model of “focused protection” for those most vulnerable could be harder to apply to the US, because a far higher proportion of obese Americans are at risk. In other words,”allowing most of the population to return to life as normal is going to require confining a lot of people to their homes for the duration — judging by the diabetes numbers, maybe twice as many as in Sweden, as a proportion of the population. As Authers puts it “that isn’t feasible.“
3. These 5 factors make it more likely you’ll suffer from ‘Long Covid’
- A new study has identified the main factors that make it more likely that patients will suffer long term from the coronavirus.
- “Long Covid” is the term given to people who recover from coronavirus but continue to suffer from a wide range of symptoms, such as shortness of breath, migraines and chronic fatigue.
- A new analysis by researchers at King’s College London, using data from the COVID Symptom Study app, shows that 1 in 20 people with C19 are likely to suffer symptoms for at least eight weeks.
- The study, published Wednesday, looked at data from 4,182 users of the COVID Symptom Study app who had tested positive for the virus and had been consistently logging their health.
- The team found that older or overweight people, women, those with asthma and those with a greater number of different symptoms in the first week of their illness were more likely to develop “long Covid.”
- Delving into the risk factors more closely, the study found that long Covid affects around 10% of 18-49 year olds who become unwell with C19, with the percentage rising to 22% for those over 70s.
- Weight also plays a role, with it affecting people with a slightly higher average body mass index.
- Women were much more likely to suffer from long Covid than men (14.5% compared with 9.5%), but only in the younger age group.
- The researchers also found that people reporting a wide range of initial symptoms were more likely to develop long Covid, as were people with asthma, although there were no clear links to any other underlying health conditions.
- As for the commonly reported symptoms of long Covid, the research identified two main symptom groupings; One was dominated by respiratory symptoms such as a cough and shortness of breath, fatigue and headaches.
- The second grouping “was clearly multi-system, affecting many parts of the body, including the brain, gut and heart,” the study said.
- The findings are due to be published as a preprint on medRxiv, which distributes unpublished eprints about health sciences and have not been peer reviewed. The researchers have used their findings to develop a model that can predict who is most at risk of long Covid by looking at an individual’s age, gender and count of early symptoms.
- The lead researchers, Dr. Claire Steves and epidemiologist Tim Spector, said the study could be used to help target early interventions and research aimed at preventing and treating long Covid.
- “It’s important we use the knowledge we have gained from the first wave in the pandemic to reduce the long-term impact of the second,” said Steves, a geriatrician.
- “This research could already pave the way for preventative and treatment strategies for long Covid. We urge everyone to join the effort by downloading the app and taking just a minute every day to log your health.”
- Long Covid is by no means a universal experience, and in fact many people who have contracted the coronavirus have had a mild illness or were asymptomatic.
- The King’s researchers found that while most people with Covid reported being back to normal in 11 days or less, around 1 in 7 (13.3%, 558 users) had symptoms lasting for at least four weeks, with around 1 in 20 (4.5%, 189 users) staying ill for eight weeks and 1 in 50 (2.3%, 95 users) suffering for longer than 12 weeks.
- “These are conservative estimates, which, because of the strict definitions used, may underestimate the extent of Long-Covid,” the researchers cautioned.
- The U.K.’s National Health Service announced earlier in October that it will provide specialist help at clinics to those suffering from long-term symptoms of the coronavirus.
4. 20% of verified coronavirus patients did not develop immunity
- Only 80% of people who tested positive for coronavirus had antibodies to the virus, according to a report published Monday by the Central Bureau of Statistics, the Health Ministry and the Gertner Institute.
- The results mean that a percentage of people who develop asymptomatic or even mild cases of the virus could contract it again.
- The report was based on a serological survey conducted between June and August in the haredi (ultra-Orthodox) community of Bnei Brak. The city has had some of the highest rates of infection in the country.
- The survey also found that the number of people who tested positive for antibodies increased with the number of sick patients, thought not proportionally.
- The survey also revealed additional relevant findings, such as people with larger families were more likely to spread the virus to each other. In families of eight people or more with at least one verified patient, 11.2% of members were found to have antibodies, meaning they had contracted the virus. The number in smaller families was only 7.9%.
- This also proved true in buildings and communities. The survey showed that people who lived in the same apartment building as someone with coronavirus was more likely to contract the disease than someone who did not – 10.2% of people in buildings with a verified patient had antibodies versus 7.2% within the general population at the time this part of the study was conducted.
- There were also noticeable differences between age groups: Of those aged 7-14, 8.3% had antibodies, versus those 15-24 of which 13.8% had antibodies, and those over the age of 60, of which only 5.3% had immunity.
- Also, in line with international research, 12.1% of men developed antibodies, meaning they caught coronavirus, versus 6.2% of women.
- Moving forward, the researchers said that they would need to screen the people who showed they had antibodies again to see how long those antibodies last.
5. How does Covid-19 affect the heart?
- Scientists are continuing to explore the toll the virus takes on the cardiovascular system. Three new papers released Monday lay out what’s been learned so far
- People who already have heart disease are at higher risk for heart rhythm disturbances and blood vessel-blocking clots. Heart muscle injury, which occurs in about 1 in 4 hospitalized C19 patients, is tied to both a greater need for a ventilator and to death, one study finds.
- People with cardiovascular problems who become infected experience more severe illness and complications, struggling to breathe and having small blood clots form in the lungs, heart, and kidney. “Although most patients recover, those who survive severe illness may experience persistent physical and psychological disabilities,” the authors of another paper write.
- And in a third paper, experts break down four pre-existing problems that can make C19 infection worse: obesity, high blood sugar, high cholesterol, and high blood pressure, which they collectively call Covid-related cardiometabolic syndrome. Medications, better diet, and increased exercise are tried and true remedies in the long term, but “lessons learned from the C19 pandemic support shorter-term benefits of these interventions,” the study says.
G. Back to School!?
1. Keeping C19 out of classrooms
- As the C19 virus continues to spread around the globe, studying aerosol and droplet transport within different environments can help establish effective, physics-informed measures for virus mitigation. One of the most important environments to gain a rapid understanding about C19’s spread is inside the school classroom.
- Flow velocity distribution and particle size are key in aerosol transport, which is one of the main ways C19 spreads, when aerosol particles are released during exhalation, talking, coughing, or sneezing.
- In Physics of Fluids, from AIP Publishing, University of New Mexico researchers used computational fluid-particle dynamics to explore aerosol transport within an air-conditioned classroom model. They discovered opening windows increases the fraction of particles that exit the system by nearly 40%, while also reducing aerosol transmission between people within.
- “Nearly 70% of exhaled 1-micron particles exit the system when windows are open,” said Khaled Talaat, one of the authors. “And air conditioning removes up to 50% of particles released during exhalation and talking, but the rest get deposited onto surfaces within the room and may reenter the air.”
- Particles are transmitted in significant quantities (up to 1% of exhaled particles) between students — even at 2.4 meters (7.8 feet) of separation distance because of air flow.
- “The aerosol distribution within the room isn’t uniform, because of air conditioning and source location,” said Talaat. “Student position within the room affects the likelihood of transmitting particles to others and of receiving particles.”
- The researchers were surprised to find that glass droplet screens placed in front of desks significantly reduced the transmission of 1-micron particles from one student to another, according to Talaat.
- “Screens don’t stop 1-micron particles directly, but they affect the local air flow field near the source, which changes the particle trajectories,” he said. “Their effectiveness depends on the position of the source with respect to the air conditioning diffusers.”
- For school reopenings, the group recommends keeping windows open when possible and installing glass screens in front of desks. Students at higher risk of C19 complications can be seated where they are exposed to fewer particles, which will depend on the air conditioning layout within the room.
- “In our model, the back corners are the safest spots,” Talaat said.
- The group stresses the importance of sanitizing hands — even without contact with other people’s belongings — because “particles can be transmitted from one student to other students’ desks or clothes, etc., even when keeping separated by a distance of 2.4 meters,” he said.
- Their work also highlights the importance of effective filtration and sterilization systems within air conditioners.
- “Given the significance of air conditioning, there is potential for optimization of HVAC systems within classrooms to maximize particle removal, while providing adequate ventilation,” Talaat said.
2. More Schools Are Reopening as C19 Cases Rise Nationwide
- After starting school virtually because of the coronavirus pandemic, some districts are opening doors and allowing students back for the first time.
- Public schools that opened for in-person learning this month, or plan to, range from suburban districts in North Carolina’s Wake County to city systems such as Indianapolis; Des Moines, Iowa; and Miami-Dade in Florida. Schools in Houston plan to welcome students inside starting Monday.
- New daily cases of C19, the illness caused by the new coronavirus, have been trending up nationwide since mid-September, but relatively few have been found in K-12 schools that have been open already. School leaders are finding they can successfully enforce measures such as mask wearing, social distancing and cleaning routines.
- Determining when and how to bring children back to classrooms has been a fraught process in many places, as district chiefs and families consider the risk of illness against loneliness, the need for parents to work and the fear that students might lose academic skills.
- Some districts that began with a mix of online and in-person learning are now increasing face-to-face days. That includes New Canaan, Conn., where Superintendent Bryan Luizzi is deeply aware of how dangerous the new virus can be. His 79-year-old father died of C19 last spring, four days after diagnosis.
- Mr. Luizzi has been determined to bring students back for a full schedule, after they started in August with two or three days a week on campus. For the first time since March, on Thursday its middle school welcomed nearly all of its 1,350 students back for face-to-face instruction every day.
- “The work we do in school really, really matters and it’s not the same when they’re not here,” Mr. Luizzi said as students in masks hopped off orange buses. “This is their life.”
- New Canaan, a wealthy town, has spacious school grounds, money for safety measures and a low community-infection rate—about three cases per 100,000 people, according to state data. Reopening decisions are harder in districts facing higher virus rates, budget cuts, poor ventilation or reliance on public transportation, where staff and students worry about additional exposure.
- In the Highline school system near Seattle, for example, officials decided this month to remain fully remote through at least Jan. 28. Superintendent Susan Enfield told families the district didn’t meet the Washington state threshold for considering reopening: fewer than 75 new C19 cases per 100,000 residents in a 14-day period. Local authorities predict a winter surge.
- ‘‘I am desperate to get children back in school,” Ms. Enfield said Thursday in a webinar for educators and policy makers run by the American Enterprise Institute, “but I cannot in good conscience say to my staff and teachers and families and kids, come back in person when our rates are that high.”
- There is no comprehensive national data showing how many of the nation’s 13,000-plus K-12 public school districts have opened for in-person instruction or how many students in each district have contracted C19. Few districts conduct systematic virus testing, so some cases might not be known.
- About 415,700 children ages 5 to 17 years old have had C19, or about 7% of U.S. cases in which the patient’s age was available, according to the Centers for Disease Control and Prevention. Sixty-one children in that group have died [NOTE: A survival rate of 99.985%].
- Roughly 56 million children attend prekindergarten through 12th grade.
- About 49% of districts planned to start fall with in-person classes, 27% online, and 12% in a hybrid model, according to an August sampling of 477 districts by the Center on Reinventing Public Education, a research group. It found students in rural communities were far more likely to have access to fully in-person instruction than suburban and city students.
- Since reopening for the fall, some districts have reported scattered classroom quarantines or temporary building closures—including New York City and the Cherokee County district in suburban Atlanta—when the new virus surged in the area or was found among staff or students.
- But generally, the risk of getting the virus at school appears to be low, said Emily Oster, a Brown University economist collecting nationwide data. She is working with data scientists and educators’ associations to create the C19 School Response Dashboard.
- It showed an overall rate of about 1.5 infections among 1,000 students in districts with in-person classes during two weeks in late September. It found 2.5 infections among 1,000 employees.
- ‘‘This suggests the risks to kids from going to school are small and they’re in the range of the Covid risks you are probably taking in other settings,” Ms. Oster said. Researchers caution the data set reflects only about 213,000 children, and districts with successful virus-prevention steps might be more likely to take part in the voluntary project.
- It is hard to know which reopening safety strategies work best because there is no data to compare infection rates in schools that take steps such as cutting class sizes or shortening in-person schedules to outcomes in schools that don’t. “This severely limits our ability to give additional guidance to schools,” said Wendy Armstrong, an infectious-disease expert at Emory University School of Medicine in Atlanta.
- Considering information available so far, however, Dr. Armstrong said in a media briefing that “We have not seen a massive superspreading event” in schools at the K-12 level.
- Some researchers see encouraging signs in Texas. Its Department of State Health Services reports 9,719 student cases since school began in early August, and estimates just over 2.1 million students on campus—an infection rate well below 1%. By comparison, about 8% of people getting tested in Texas have positive results, by state data.
- New Canaan, which has a mix of upscale shops and rolling lawns about an hour from New York City, has about 4,200 children in its public schools. So far, five students and two staff members have tested positive: Only one, who is asymptomatic, remains out of school. Officials traced the infections to origins off campus, including parents and a hockey team.
- The district spent nearly $2 million on masks, technology, staff additions, Plexiglas barriers and furniture storage to create more classroom space, said Mr. Luizzi, the superintendent. Money saved from lower bills for utilities and buses during the spring pandemic lockdown covered those costs, he added.
- By Thursday, all grades will be back full-time. “Having kids come back gradually helped to build trust,” said Katrina Parkhill, chair of the school board.
- Students said they were happy to be with friends and off Zoom. That includes Lisa Tremblay, an eighth-grader who showed up for school on Thursday with a viola and a novel full of homework notes. “It’s almost back to normal,” she said.
3. In NYC Schools, Only 18 Positive Coronavirus Tests Out of 10,676
- For months, as New York City struggled to start part-time, in-person classes, fear grew that its 1,800 public schools would become vectors of coronavirus infection, a citywide archipelago of super-spreader sites.
- But nearly three weeks into the in-person school year, early data from the city’s first effort at targeted testing has shown the opposite: a surprisingly small number of positive cases.
- Out of 16,348 staff members and students tested randomly by the school system in the first week of its testing regimen, the city has gotten back results for 16,298. There were only 28 positives: 20 staff members and eight students.
- And when officials put mobile testing units at schools near Brooklyn and Queens neighborhoods that have had new outbreaks, only four positive cases turned up — out of more than 3,300 tests conducted since the last week of September.
- New York City is facing fears of a second wave of the virus brought on by localized spikes in Brooklyn and Queens, which have required new shutdown restrictions that included the closure of more than 120 public schools as a precaution, even though few people in them have tested positive.
- Roughly half of the city’s students have opted for hybrid learning, where they are in the building some days, but not others. The approach has enabled the city to keep class sizes small and create more space between desks.
- Since then, large school districts across Florida have opened for in-person learning, too. Some wealthier districts in the New York suburbs declined to take this step, worried that it was too risky and logistically challenging.
- The city’s success so far could put much more pressure on other districts that have opted for only remote instruction to start considering plans to bring their children back as well.
- “That data is encouraging,” said Paula White, executive director of Educators for Excellence, a teachers group. “It reinforces what we have heard about schools not being super spreaders.”
- So far, it is also good news for Mayor Bill de Blasio, who has staked much of his second-term legacy on reopening schools for in-person learning during the pandemic.
- While public health experts said the data was encouraging, they also cautioned that it was still early.
- In general, maintaining low levels of infection at schools would depend on how well New York City does in holding off a broader spread in the population.
- Also, some experts have called for much more frequent random testing in all schools — something that city officials are considering — in order to increase the odds of discovering an outbreak early.
- So far, most coronavirus testing for school workers has taken place at city-run sites outside the purview of the education department.
- Out of 37,000 tests of staff members at city sites, 180 were positive, a city official said.
- According to separate data reported to the state by local school districts, 198 public school students in New York City have tested positive since Sept. 8. (Gov. Andrew M. Cuomo in early September ordered those conducting coronavirus tests to collect school information on children, but so far compliance has been spotty, state officials said.)
- The city’s new schools testing regimen, which began Oct. 9, calls for 10 to 20 percent of the school population to be tested once a month, depending on the size of the school. The city is applying this testing to its 1,600 traditional public schools; the city’s 260 charter schools are not included.
- Some researchers have questioned the efficacy of that approach, saying it could miss a large outbreak.
- “It’s great that New York City is doing some level of random testing,” said Dr. Ashish Jha, dean of the Brown University School of Public Health. “It’s not at the level that would be ideal.”
- One study recommended testing half the students twice a month.
- Michael Mulgrew, president of the teachers union, said the city is looking to increase testing to as much as three times a month citywide. Such frequency, he said, would be “much more valuable” in terms of keeping the virus in check.
- A spokeswoman for the city’s education department cast the discussions to increase testing as merely exploratory.
- A positive test of a student or teacher causes the city to spring into action. Under the rules, one case can cause the closure of a classroom. Two or more cases in separate parts of the same school can prompt a temporary schoolwide closure. At least 25 schools have temporarily closed since classes began. But only three were closed as of Friday.
- Mr. Cuomo also ordered an increase in testing in schools around hot spots — from once a month to once a week. And on Thursday, he announced that the state would send 200,000 rapid antigen tests to New York City to help in the effort.
- “This is a tremendously tricky balancing act,” Dr. Jay Varma, senior adviser for health to Mr. de Blasio, said in an interview. “We really chose the most conservative approach possible.”
- The city’s school testing program depends on parents consenting to having their children tested. If officials find that a given school does not have enough approved students to collect an adequate sample, students who are randomly selected for testing but whose parents refuse consent could be forced to study remotely.
- So far, only about 72,000 parents have returned consent forms, the school’s chancellor, Richard A. Carranza, said at a City Council hearing on Friday. That is out of about 500,000 children who are attending in-person classes at least one day a week.
H. The Road Back?
1. Heading Back to Work? Here’s What You Need to Know
- Since March, many American professionals have been hunkered down at home, juggling labor and life in new and occasionally exhausting ways. Now, however, some companies are beginning to bring us back to our corporate offices, with all the attendant anxieties (elevators!) and opportunities (a defensible reason to escape the kids again!) that brings.
- With the return to work—or at least to a hybrid of work and WFH—new issues are surfacing. In this collection of popular stories that The Wall Street Journal has published in recent weeks and months, we look at a few such issues, from what to wear to the office in this odd post-sweatpants moment to more serious matters, like whether to tell your boss about the toll the pandemic has taken on your mental health. But first, we examine a fixture of professional life from the before-times: happy hour and why some people are reclaiming the tradition even before they’re fully back in their cubicles.
- As the coronavirus has forced many to work from home, it’s also disrupted a fixture of office life—afterwork drinks. While virtual happy hours have helped keep colleagues in touch, many are gingerly trying to get back to traditional socializing and the informal networking that Zoom meetings can’t replace. Keeping that camaraderie going, some say, is “incredibly important.”
- A more serious dilemma that comes with the return to work: Even before a Covid-19 vaccine is available to the general U.S. public, many businesses are wondering whether they can or should require their workforce to be vaccinated. Here’s a look at the legal considerations around potential mandatory vaccine policies.
- Men’s work lives have changed in the Covid Era and so has the professional dress code they once adhered to. What should guys wear on a Zoom interview? What masks are appropriate for the boardroom? When is it OK to wear a suit again? Here, we ask the experts to solve seven men’s style conundrums
- Mental-health issues have soared during the pandemic and companies are providing benefits. But is it risky to reveal your anxiety or depression to your boss? Before asking for accommodations, check out these tips on thinking through whom to talk to and what you need.
- While many American workers welcome a return to office life, crowded commuter trains and city buses are still scary. Solo trips across town—on everything from scooters to futuristic unicycles—can seem less risky. But which form of “micromobility” might suit you best?
- Women splitting time between video conferences, remote schooling and occasional trips to newly opened offices face a dilemma: How to dress for these complicated days? Experts and working women assemble fall wardrobes that combine WFH comfort and professional polish.
I. Projections & Our (Possible) Future
1. What will winter bring?
- A third surge of coronavirus cases has gripped the U.S. — with outbreaks across nearly the entire country — inviting fears that the approaching winter may make a dangerous situation even worse.
- But how can we know what the colder months will bring?
- We don’t have a crystal ball, but Alaska is emerging as a possible test case for what winter may be like in the U.S.
- During the summer months, when the virus pummeled the South and the West, Alaska kept the virus in check, largely because of a top-notch containment effort. Alaska conducted more tests than almost any other state and marshaled an army of contact tracers to track every person who tested positive. At the time, Alaska was recording some of the fewest cases per capita in the U.S.
- Now, temperatures are once again dropping below zero, sunset greets the evening commute, and people are heading indoors to eat, drink and socialize — giving the virus new opportunities. The weekly case average in Alaska reached its highest point of the year on Friday, and the percentage of people who have tested positive has doubled in recent weeks. Tribal villages have been forced into lockdown in parts of the state, and contact tracing has come under strain.
- In addition to thriving indoors, the coronavirus may be more virulent in colder weather and lower relative humidities. Research has shown that some viruses persist longer in colder and drier conditions and that aerosolized viruses can remain more stable in cooler air. Viruses can replicate more swiftly in such conditions, and human immune systems may respond differently depending on seasons.
- In Alaska, winter weather has complicated efforts to send supplies to small villages with outbreaks, and may prevent medevac flights from reaching them. Gov. Mike Dunleavy said that the state was continuing to build out supplemental hospital capacity should it be needed.
- “It’s going to be a very tough fall and winter for the entire world,” he said.
Source: New York Times Coronavirus Briefing
2. Can a 2-Week ‘Circuit Breaker’ Lockdown Curb C19? The U.K. May Be About to Find Out
- The coronavirus is having its way with the United Kingdom—a fact that is told starkly by the numbers. The 21st most populous country in the world, the U.K. is 11th in total number of C19 infections—and climbing fast. Its daily infection rate is doubling every seven to eight days in some regions, more people are now hospitalized there than on March 23 (when the country went into general lockdown), and in some regions, hospital beds and intensive care units are at 90% capacity. With cold weather coming on and flu season beginning, things look darker still.
- “We could sleep-walk into a long and bleak winter,” warned opposition Labour Party leader Sir Keir Starmer in an address last week.
- The answer, hard as it may be to sell to a COVID-weary public, is another lockdown—sort of. British policymakers are increasingly turning to what’s known as a “circuit-breaker” strategy: a short, sharp lockdown of just two to three weeks to get ahead of the virus and, if nothing else, buy a little time.
- Some parts of the U.K. are already introducing them. On Monday, Wales announced a “fire break” lockdown for two weeks from Friday, with residents ordered to stay home wherever possible. Both Scotland and Northern Ireland have shut pubs and restaurants and limited travel, and are considering even stricter regulations. Now the national government in Westminster is being urged to introduce blanket restrictions on the entire country.
- The idea’s advocates argue that it has multiple advantages: It hits the brakes hard and fast on the pandemic’s spread; it eases the pressure on the National Health Service (NHS) and its hospitals; and it imposes restrictions with a known end date, making compliance among the general public far likelier than it was during the earlier quarantine period, which ran on indefinitely.
- “The biggest difficulty people have is the uncertainty,” says Michael Tildesley, professor of infectious disease modeling at the University of Warwick. “If you can say to them, ‘O.K., you do this for two to three weeks and come hell or high water we’re going to lift the restrictions afterwards,’ you have a greater likelihood of compliance.”
- It’s not just psychology in play here. It’s economics, too. “For businesses, the certainty of when and how long they will be closed gives room for planning, and for government to put in the appropriate financial support,” says Graham Medley, professor of infectious disease modeling at the London School of Hygiene and Tropical Medicine.
- The biggest epidemiological goal of the circuit breaker approach is to reduce what’s known as the R of the pandemic—the number of people any one infected person goes on to infect in turn. When the R is above one, you’re in an exponential growth phase; when it’s below one you flip to a state of exponential reduction. Switching from above one to below one even for a short period is a powerful way to buy time.
- “It’s doesn’t just put things on pause,” says Tildesley, “it hits the rewind button.”
- Indeed it does. As a study by the Welsh government points out, trading two weeks of viral increase for two weeks of viral “decay” could put the pandemic back by 28 days or more. That could not only curb the infection rate, but save a lot of lives. According to estimates by Medley, a two-week lockdown would lower deaths from 79,800 at their current projected rate to 39,300.
- “The rise in hospitalizations, and then deaths, is exponential,” says Medley. “Health systems cannot cope even with the early stages of these epidemics. Any kind of break or lockdown reduces transmission.”
- If a nationwide circuit-breaker move is going to happen, it is likely to happen soon. Schools in much of the U.K. begin a mid-term vacation Oct. 26, meaning lockdown could come at a time when students wouldn’t be in class anyway. Parents should benefit as well, since they would not be scrambling for childcare alternatives. Most importantly, the children could benefit not just physically—reducing their risk of exposure to the virus—but psychologically.
- “I believe strongly that there is long-term damage to kids from spending too much time out of school,” says Tildesley.
- Key to making a national circuit-breaker period work is managing expectations and messaging smartly. The two-week period of any short-term quarantine is more or less the same as the incubation period for the virus, which means that throughout that entire fortnight, infection rates would keep right on rising, as people who contracted the virus before the lockdown begin testing positive. The government is thus well-advised to make it clear to Britons that they should not expect to see any benefits from the circuit-breaker approach until after the quarantine ends.
- Epidemiologists, who know better how to read the numbers, may benefit from a short-term lockdown too. As the wildfire of national infections abates it can be easier to identify local brushfires, improving contact tracing and giving the NHS a better sense of how to mobilize its resources.
- The British public seems in favor of some kind of dramatic measure. According to The Telegraph, 54% of Britons surveyed on Oct. 13 said that the government should have imposed a lockdown in September, against just 28% who did not. A circuit-breaker, with its limited scope, would seem to be both a political and epidemiological winner—but only as long as that end point is honored.
- “My worry,” says Tildesley, “is that the lockdown will keep getting extended and people will say, ‘I’m not doing this anymore.’” A circuit breaker with an off setting is no good at all if it doesn’t have an honest on as well.
1. Swedish cities finally face coronavirus lockdowns… but authorities say they will be VOLUNTARY
- Parts of Sweden hardest-hit by the coronavirus are facing localized voluntary lockdowns.
- Authorities are drawing up guidelines which include advising Swedes not to go to bars, restaurants and non-essential shops.
- It marks a shift for the country which previously decided not to put its citizens into lockdown but instead had a ‘lighter’ approach to tackling the pandemic. Coronavirus cases have been gradually increasing since the start of September, dashing Sweden’s hopes for immunity.
- Last week, a seven-day average of 65 per million people per day was reported to the European Centre for Disease Prevention and Control on Friday. This is compared to 71, 40 and 25 cases per million in Denmark, Finland and Norway.
- Covid-19 hotspots including capital city Stockholm, Uppsala, Orebro and Jamtland could be advised to avoid physical contact with anyone outside their household, as well as travel and visiting those in more vulnerable categories.
- Compliance will be voluntary, with the Swedish government not handing out fines or prison sentences for those who violate the rules.
- Jamtland, in central Sweden, last week recorded 95 new cases for every 100,000 inhabitants.
- Bitte Brastad, chief legal officer at the agency, said the new measures were ‘something in between regulations and recommendations’ and Dr Nojd confimed further measures would be imposed if contact tracing shows links between infections and certain areas.
- The Scandinavian country was a talking point during the pandemic for its resistance to imposing a national lockdown like its European neighbors.
- Much of Europe has introduced measures such as shutting or ordering early closing of bars, but now the surging infection rates are also testing the resolve of governments to keep schools and non-COVID medical care running.
2. A vicious cycle of lockdowns would condemn Britain to terminal decline
- Please, please, Prime Minister, do not lock us down again. Do not listen to the unidimensional, anti-economic, risk-averse groupthink from Sage. Ignore Sir Keir Starmer and Sadiq Khan’s shameless politicking.
- A “circuit-breaker” is doublespeak for another lockdown, and cannot be a sustainable answer: the virus would only be temporarily suppressed, with transmission bouncing back as soon as the restrictions were lifted again. If the NHS cannot cope now, it never will.
- Once one accepts the logic of shutting down society each time Covid reaches a certain prevalence, a third and perhaps even fourth lockdown become inevitable before the winter is up. It would lead to the most expensive game of whack-a-mole ever played.
- A vicious circle of stop-go lockdowns would be a catastrophic indictment of Government policy, an admission of total defeat, a victory of fear and emotion over reason, an appalling signal that Britain has now become so culturally dysfunctional, so decadent as to be utterly incapable of any rational cost-benefit analysis.
- We would no longer be a free society tolerating an exceptional, temporary shutdown to allow our scandalously unprepared establishment to learn to manage a terrible situation. Instead, we would have transitioned to a world of permanent emergency, a wartime society whereby individual rights and lives were permanently suppressed for an ill-defined, ever-shifting “national interest”.
- A new principle would have become established: that the Government has the right and even the obligation to lock us down at the first sign of any new epidemic, even one that doesn’t truly threaten the survival of our society. Johnson must resist going down that route with every fibre of his being.
- This is not to say that there wouldn’t be some gains from locking down again. Sharply reducing social contacts would slow the spread of the virus. But these benefits would be limited, uncertain and temporary, and some of them could be achieved in a less costly fashion. Any upside would need to be set against gigantic, guaranteed economic, social, personal and metaphysical costs.
- The main rationale for a “circuit-breaker” – that it would buy yet more time for “one last push” on testing, the app, tracing and a vaccine – is tragically delusional. Even the French and Germans have failed to introduce effective testing and tracing, suggesting that the endeavor may be an elusive El Dorado, at least for now.
- Our own system has improved beyond recognition, but lack of compliance and its own inherent limitations mean that it will almost certainly not be able to keep the reproductive rate below 1. Just as depressingly, there is unlikely to be a usable mass vaccine this year.
- Yes, a few deaths might be avoided by spreading out ICU admissions to our hopelessly ineffectual NHS. Yes, a few others – maybe even up to 20,000 in a best-case scenario – might be saved as a result of multiple lockdowns if an effective vaccine suddenly, miraculously materializes by April.
- But, in reality, most deaths would not be avoided, merely delayed, and there will be plenty of additional fatalities caused by the lockdown itself – including out of despair – to set against that. Unemployment would have surged, tens of thousands more businesses ruined, family and community life laid to waste, and immense misery created. What kind of society is ready to destroy so much to save so little?
- If he agrees to the lockdown fanatics’ every demand, Boris Johnson’s legacy would have been to sweep away the Eurocrats, and cut back on the juristocrats, just to replace them with a new medicocracy. A gang of well-meaning scientists and doctors would be empowered to impose their narrow vision of the good on the rest of us, the first therapeutic, zero-risk state in world history.
- But public health experts don’t have the full perspective. We can’t go on like this for much longer. The first lockdown probably increased our debt to GDP ratio by 20 percentage points; adding yet another 20 per cent over the winter would weaken us severely.
- We could survive that, of course, but what firepower would we have left when the next calamity hits us? What about another virus – Covid-24, say? And the one after that? Or what about the next bad flu season? We would be all but bankrupt by 2030, with a dollar, sterling and euro crisis on our hands.
- Lawrence Summers, the economist, estimates the cost of Covid will reach 90 per cent of GDP for America alone – a mind-boggling $16 trillion or $200,000 per family. This is “four times larger than the output loss of the Great Recession, twice the cost of all wars since 9/11, and roughly the cost of climate change in the next 50 years”. We need to find ways of minimizing this cost for future pandemics, or we will be condemned to impoverishment, social decay and geopolitical decline.
- This latter point is ably demonstrated by the IMF’s latest forecasts. It expects the UK to suffer a 9.8 per cent fall in GDP this year, identical to France, better than Italy or Spain. Germany and America will shrink but by less. Astonishingly, however, China’s economy will actually grow this year. This pandemic has accelerated many trends, not least the transfer of power from West to East. South East Asian countries are among the few to have kept the costs of the virus to manageable levels, and China is laughing.
- Britain and the West have two choices. We could relearn to live with death, as we did in the post-war years when big flu epidemics killed tens of thousands. The alternative is to embrace the South Korean approach. We will need to invest a fortune in pandemic preparedness and technology, and pounce on the next virus as soon as it emerges. Ruthless, brutal quarantining, isolation and hugely superior tracking and tracing will be necessary.
- Can we do it? Would we have to give up too much privacy and liberty? Are we nearing the twilight of the West, defeated by its fragility, its inability to cope with the kind of virus that our forebears shrugged off?
- If we don’t get our act together, this will not just be Asia’s century but also the West’s last as any kind of beacon to the rest of the world. Boris Johnson needs to show that Britain, for one, hasn’t yet given up.
3. The WHO Warned in 2011 Against a “Culture of Fear”
- A fine feature of the decentralized network of anti-lockdown Twitter is that it turns up fantastic bits of research that would otherwise go unnoticed. In this case, Kulvinder Kaur MD, president of Concerned Ontario Doctors, discovered an extraordinarily truth-telling bulletin from the World Health Organization that was released July 2011. Its prescience is incredibly obvious. It appeared in times when what we might call the lockdown industry was gaining steam.
- This movement was born in the early 2000s with computer scientists who imagined that their agent-based models should replace medical advisories in the event of a pandemic. The Bush administration acquiesced to their ideas in 2006, despite the protests from responsible public health experts. After that, they organized conferences, published in journals, and generally closed ranks around a fantastic vision of central plan, all well-funded through public money and private philanthropy from the Gates Foundation (Bill Gates, knowing next to nothing about viruses or public health concerns, has been a lockdowner for many years).
- All these years later, they got their chance to implement a dangerous social experiment in lockdowns.
- In 2011, the World Health Organization saw what was developing and issued a powerful warning, authored by Luc Bonneux (Netherlands Interdisciplinary Demographic Institute) and Wim Van Damme (Institute of Tropical Medicine). It was a strong attack against the “culture of fear” that could be fomented in the future just as it was in 2006 and 2009. It said plainly that the next pandemic should be treated as we have in the 20th-century past, with calm, not panic, and with a broad-minded focus on public health in a holistic sense.
- Moreover, the memo warned of what we might call the Public Choice elements of the urge to lock down: flu specialists sound unwarranted alarms in order to attract media attention and funding, vaccine makers and marketers looking for government subsidies, and other interest groups that might irresponsibly use a future pathogen.
- In times when governments around the world are fomenting fear, turning citizens against each other, stigmatizing those with disease, and teaching people to regard dignified human persons as nothing more than disease vectors, this element of wisdom is a ray of light.
- The repeated pandemic health scares caused by an avian H5N1  and a new A(H1N1)  human influenza virus are part of the culture of fear. Worst-case thinking replaced balanced risk assessment. Worst-case thinking is motivated by the belief that the danger we face is so overwhelmingly catastrophic that we must act immediately. Rather than wait for information, we need a pre-emptive strike. But if resources buy lives, wasting resources wastes lives. The precautionary stocking of largely useless antivirals and the irrational vaccination policies against an unusually benign H1N1 virus wasted many billions of euros and eroded the trust of the public in health officials. The pandemic policy was never informed by evidence, but by fear of worst-case scenarios.
- The WHO issued this blast due to the manufactured media and political panic that occured in both 2006 and 2009. The headlines blared about the coming danger. Statesmen the world over gave press conferences alongside various public health alarmists. The mainstream media used the occasions to get clicks and freak out. I recall both well because it was all so strange to see public officials attempting to get their populations in a state of absolute freak out despite any evidence. They got into the habit of imagining the worst-possible outcomes and broadcasting those out to people. In both 2006 (the flu never really left the bird population) and 2009 (which turned out to be no worse than seasonal), the public paid very little attention to the histrionics taking place in the public sector.
- What alarmed the WHO in those days was how public health authorities had taken a dangerous turn away from calming the public into sowing public panic.
- The memo continues:
- In both pandemics of fear, the exaggerated claims of a severe public health threat stemmed primarily from disease advocacy by influenza experts. In the highly competitive market of health governance, the struggle for attention, budgets and grants is fierce. The pharmaceutical industry and the media only reacted to this welcome boon. We therefore need fewer, not more “pandemic preparedness” plans or definitions. Vertical influenza planning in the face of speculative catastrophes is a recipe for repeated waste of resources and health scares, induced by influenza experts with vested interests in exaggeration. There is no reason for expecting any upcoming pandemic to be worse than the mild ones of 1957 or 1968, no reason for striking pre-emptively, no reason for believing that a proportional and balanced response would risk lives.
- If I’m reading this correctly, the WHO seems to be warning of the rise of a whole industry of public officials, media, and pharmaceuticals that is heavily invested in creating panic whenever the next pathogen arrives, wildly exaggerating the threat in their own industrial interests. That’s a strong charge. It seems to have been back up by the unfolding events of 2020.
- The memo continues with an offering of an alternative to the culture of fear. Officials should instead look to the evidence and manage a pandemic with clear-headed rationality.
- The opposite of pre-emptive strikes against worst-case scenarios are adaptive strategies that respond to emerging diseases of any nature based on the evidence of observed virulence and the effectiveness of control measures. This requires more generic capacity for disease surveillance, problem identification, risk assessment, risk communication and health-care response. Such strengthened general capacity can respond to all health emergencies, not just influenza. Resources are scarce and need to be allocated to many competing priorities. Scientific advice on resource allocation is best handled by generalists with a comprehensive view on health. Disease experts wish to capture public attention and sway resource allocation decisions in favour of the disease of their interest. We referred previously to the principles of guidance on health by the British National Institute for Health and Clinical Excellence (NICE), cited as “We make independent decisions in an open, transparent way, based on the best available evidence and including input from experts and interested parties.” Support from disease experts is crucial in delivering opinion, scholarly advice and evidence to a team of independent general scientists. But this team should independently propose decisions to policy-makers and be held accountable for them.
- Finally we get a beautiful closing riposte:
- The key to responsible policy-making is not bureaucracy but accountability and independence from interest groups. Decisions must be based on adaptive responses to emerging problems, not on definitions. WHO should learn to be NICE: accountable for reasonableness in a process of openness, transparency and dialogue with all the stakeholders, and particularly the public.
- What we see in this remarkable memo is identical to the ethos and import of the Great Barrington Declaration, which since its release has been treated like some kind of radical and controversial statement. Actually, the World Health Organization said the same thing in 2011 with much tougher language and more biting analytics, essentially warning that the world is being trolled by interest groups with a vested stake in panic over rational public health measures.
- What was true in 2011 is true today. More so than ever.
J. Practical Tips & Other Useful Information
1. C19’s wintry mix: Dry indoor air helps the virus spread
- It’s not just the cold, it’s the humidity.
- Winter in the northern United States will soon drive even the most diehard outdoor diners and backyard socializers indoors, bringing with them heightened risk for contracting and spreading C19. The worry is not just that people might mingle more closely inside, but that the air they breathe will make the virus more dangerous.
- Cold, dry air facilitates the spread of the coronavirus, and the social distancing that helped outside won’t be as effective indoors, scientists said.
- “I do worry about this pandemic potentially getting worse this winter,” Akiko Iwasaki, an immunologist at the Yale School of Medicine, told STAT. “All the same kind of concerns that usually apply to other respiratory infections are the same with this virus.”
- The coronavirus that causes C19 will thrive this winter for three reasons: dropping temperatures, diving relative humidity, and drier respiratory tracts. When the weather turns cold, air gets drier. And turning on the heat dries both the air and the tissues lining the airways, impairing how well mucus removes debris and invaders like SARS-CoV-2.
- Studies show significantly more infections happen and spread when the relative humidity falls from between 40% and 60% — a range typical in warmer weather — to 20%. That research draws from past outbreaks of flu and MERS, which is caused by another coronavirus. More recent case reports from the SARS-CoV-2 pandemic’s early days in China and Seattle conclude the same thing: The virus stays stable longer and finds purchase on receptors in our airways better when the relative humidity sits at a wintry 20%. That’s one reason why we catch more colds and flu in cold weather.
- Limiting the number of people in a confined space, wearing a mask, and ensuring good ventilation can help reduce the risk of infection indoors. But still, the viral particles from an infected person are unlikely to just blow away, as they might outside on a windy day. Consequently, the admonition for people to stay six feet apart may not be adequate in offices, schools, restaurants, and other indoor spaces, some scientists said. Even when social distancing outdoors, “six feet is not magic,” Iwasaki said.
- Martin Bazant, professor of chemical engineering and mathematics at MIT, urges people to think “beyond six feet,” which is how he and his colleague John Bush titled their paper posted to the preprint server medRxiv last month.
- “It was recognized early on that so-called superspreading events, which invariably occur indoors among persons separated by more than six feet, can only be explained by airborne transmission,” he said in an interview.
- Models for indoor air assume that pathogens like the SARS-CoV-2 virus are distributed uniformly throughout indoor rooms. “In such well-mixed spaces, one is no safer from airborne pathogens at 60 feet than 6 feet,” Bazant and Bush wrote.
- The Centers for Disease Control and Prevention has issued conflicting guidance. In September, the agency changed the information on its website about airborne transmission of C19, first saying it could be spread beyond six feet through droplets or small particles in aerosols produced when an infected person coughs, sneezes, sings, talks, or breathes. Three days later, CDC removed information about aerosols and distances greater than six feet, saying a draft guidance had been mistakenly posted.
- A CDC scientific brief posted Oct. 5 held to the six-foot standard: “Available data indicate that SARS-CoV-2 has spread more like most other common respiratory viruses, primarily through respiratory droplet transmission within a short range (e.g., less than six feet).” The agency also said it found no evidence of routine, rapid spread to people far away or who enter a space hours after an infectious person was there.
- “Unfortunately, 10 months into the pandemic, public health agencies are still reluctant to acknowledge airborne transmission, let alone question the six-foot rule. Official guidelines still focus on large-drop transmission in coughs and sneezes, where six feet is an arbitrary distance for those droplets to settle to the floor,” Bazant said. “Aerosol transmission was previously implicated in the spread of SARS and measles with less evidence than we have now for C19, so I am hopeful that change will come soon, as the scientific consensus grows.”
- Bazant and Bush, an expert on respiratory fluid mechanics, have created a guideline to gauge the risk of airborne transmission that takes into account factors such as exposure time, room size, ventilation, and human activity. They designed a spreadsheet and online app intended to be simple enough for public health agencies to endorse and the public to use.
- “Depending on ventilation, mask use, air filtration, and other variables, any indoor space may carry either low or high risk of transmission,” Bazant said.
- Local regulations may govern ventilation in public places, but they don’t go far enough in the view of Yale’s Iwasaki. She and others are urging the World Health Organization to add relative humidity to indoor-air standards for such public places as schools and nursing homes. “It’s really to take action by setting the standard from 40 to 60% humidity, because that’s the optimal humidity for health and respiratory infection prevention,” she said about the online petition.
- Pending such a move, there’s always the mask option indoors.
- Masks are more effective than ventilation or air filtration because they filter aerosols and large drops at their source, as a person emits them. That means either more people can safely be in a room together or they can safely spend more time there, compared to a space that has only ventilation or air filtration.
- Hospital intensive care units typically have negative air pressure ventilation — forcing out internal air — to protect their extremely ill patients, but that’s not necessarily the case for beds on regular floors, Iwasaki said, putting patients at risk.
- Two other scientists have appealed to the medical community and public health bodies to provide more guidance about precautions for indoor spaces. “Hand washing and social distancing are appropriate but, in our view, insufficient to provide protection from virus-carrying respiratory microdroplets released into the air by infected people,” Linda Morawska of Queensland University of Technology and Donald Milton of the University of Maryland School of Public Health wrote in Clinical Infectious Diseases. “This problem is especially acute in indoor or enclosed environments, particularly those that are crowded and have inadequate ventilation relative to the number of occupants and extended exposure periods.”
- Iwasaki advises people to buy humidifiers for their homes, if they can. She has always told her children to bundle up with scarves over their noses when they go out in the winter, and she herself, back when she used to travel, always wore a mask on an airplane. She had three reasons: to prevent viruses from reaching her mouth and nose, to keep them warm, and to keep them moist.
- “We don’t know where this is going to end up — we haven’t had a year with it yet,” she said about the pandemic. “I think we have to be extra cautious going into the winter.”
2. It’s Time to Talk About C19 and Surfaces Again
- Beth Kalb was worried about the pews. This summer, the century-old Catholic church she attends in a small town outside Minneapolis had, like many places, reopened its doors with new rituals of disinfection. Kalb had quickly noticed the side effects. The varnish on the pews had begun to wear, and the wood was often sticky with disinfectant, so the volunteer cleaners had started using soap and water to remove the tacky build-up. They were weeks in, and it had already come to cleaning off the cleaner. Plus, all those chemicals couldn’t be good for the people who were spritzing and wiping down the worship space after each use. As a nurse, Kalb knew the importance of handwashing, but this all seemed like a bit much. It was certainly too much for the wood.
- For Erin Berman, in Fremont, California, it was the books. In the spring, a federal project to help reopen libraries, called Realm, had commissioned tests to see how long the virus lasts on objects they lend. Researchers had borrowed materials from the library system in Columbus, Ohio, and applied an inoculum of the virus to them in a nearby lab to see how long it could remain infectious. They started mainly with books, measuring how much virus was left after a day or two, but in subsequent months, expanded to magazines and DVDs and USB drives. In August, a fourth round of tests addressed the question of placing books in stacks, rather than laying them out individually. Protected from light and drying air, the researchers were able to find virus particles on them after six days. On leather book covers, a fifth round of tests determined this month, the virus lasted at least eight days.
- The Realm organizers emphasized that none of what they were reporting was guidance—it was research, meant to inform the staff at individual libraries who were deciding what to do with all those items gathering dust, and possibly germs, in people’s homes. However, they also noted it was not possible to disinfect every page of every book. So many library staffers, after seeing the data, were considering “book quarantines” that lasted a week or more.
- Berman was aware of the practical issues raised by putting books in purgatory for so long, but she had a broader concern: that all this research was encouraging an undue fixation, or even a fear, of the objects librarians are meant to joyfully share with the public. It was hard to understand what those numbers—the number of days, the number of viral particles that remained—actually meant for spreading C19 via books, but their very existence had generated anxiety among her coworkers. And she suspected that it was drawing focus away from all the other things she and her colleagues had to do to reopen safely—to reimagine a community space in which people could no longer safely linger, in which social connection would now be mediated by Plexiglass. “I started to get very frustrated. I’m thinking, ‘We’re librarians. We should be doing research,’” Berman says. “Of all the industries, we should not be operating in fear.”
- For Emanuel Goldman, a virologist at Rutgers University, the worries began with the gentle nagging of his elderly mother-in-law. “She was telling me, ‘Wipe down this, wipe down that,’” he says. He had been obliging at the start of the pandemic. The requests seemed reasonable—a set of small acts to keep his household safer. He knew from other viruses that fomite spread—the technical term for passing on a virus via objects—was possible, and at that time the Centers for Disease Control and Prevention had little guidance on SARS-CoV-2. But as he delved into the research himself, he grew concerned. Despite all the fixation on how long and how much virus lasts on surfaces, there wasn’t much evidence at all that it was relevant to how C19 actually spread. In July he laid out those concerns in a tersely worded commentary in The Lancet titled “Exaggerated risk of transmission of C19 by fomites.”
- “In my opinion, the chance of transmission through inanimate surfaces is very small, and only in instances where an infected person coughs or sneezes on the surface, and someone else touches that surface soon after the cough or sneeze (within 1–2 h),” he wrote. “I do not disagree with erring on the side of caution, but this can go to extremes not justified by the data.”
- That was months ago, and since then the scientific evidence has tipped in Goldman’s favor. And yet, here we are all the same, wiping down pews and hiding away books, among countless other disinfection rituals molded by those early perceptions. “What’s done cannot be undone,” Goldman tells me now. “And it’s going to take a lot of time and effort to turn things around.”
- In March, I wrote about what we knew at the time about our understanding of surface spread, which was very little. Nearly a year into the C19 pandemic, it’s time to ask: What do we know now?
- The first widely covered study on fomites and C19, released as a preprint in March by researchers at the University of California, Los Angeles, the National Institutes of Health, and Princeton, was a look at how long the novel coronavirus lasted on different kinds of surfaces. At the time, little was known about how the virus was transmitted, so the question was important. Depending on the material, the researchers could still detect the virus after a few hours on cardboard, and after several days on plastic and steel. They were careful to say that their findings only went as far as that. They were reporting how quickly the virus decayed in a laboratory setting, not whether it could still infect a person or was even a likely mode of transmission.
- But in the hazy panic of the time, many people had already taken up fastidious habits: quarantining packages at the door, bleaching boxes of cereal brought back from the store, wearing hospital booties outdoors. A single set of research results didn’t start those behaviors, but—along with other early studies finding the virus on surfaces in hospital rooms and on cruise ships—it appeared to provide validation.
- Dylan Morris, a mathematical biologist at Princeton who coauthored the paper, recalls watching what he calls “the great fomite freakout” with frustration. The number of days the virus remained detectable on a surface in a lab wasn’t useful for assessing personal risk, he says, because in the real world, that amount would depend on how much there had been to start with and on environmental conditions that they did not test. Plus, the amount of remaining virus doesn’t tell us much about whether it could reasonably get into someone’s airways and cause an infection. “People really picked up on those absolute times to detectability,” he says. “Everyone wants to know the magical time when something becomes safe.” In subsequent research, he says he’s avoided giving hard temporal cutoffs.
- Since March, additional studies have painted a picture that is much more subtle and less scary. But like that first study, each can be easily misinterpreted in isolation. One clear takeaway is that, given an adequate initial dose, some amount of the virus can linger for days or even weeks on some surfaces, like glass and plastic, in controlled lab conditions. Emphasis on controlled. For example, earlier this month, an Australian study published in Virology Journal found traces of the virus on plastic banknotes and glass 28 days after exposure. The reaction to that number felt to some like a replay of March: a single study with a bombshell statistic sparked new fears about touchscreens and cash. “To be honest, I thought that we had moved on from this,” says Anne Wyllie, a microbiologist at Yale University.
- Of course, this was another laboratory study done with specific intentions. The study was done in the dark, because sunlight is known to quickly deactivate the virus, and it involved maintaining cool, favorable temperatures. Debbie Eagles, a researcher at Australia’s national science agency who coauthored the research, tells me that taking away those environmental variables allows researchers to better isolate the effect of individual factors, like temperature, on stability. “In most ‘real-world’ situations, we would expect survival time to be less than in controlled laboratory settings,” Eagles writes in an email. She advises handwashing and cleaning “high-touch” surfaces.
- The second consistent finding is that there’s plenty of evidence of the virus on surfaces in places where infected people have recently been. Wherever there has recently been an outbreak, and in places where people are asked to quarantine or are treated for C19, “there’s viral RNA everywhere,” says Chris Mason, a professor at Weill Cornell Medicine. That makes going out and swabbing a useful tool for keeping track of where the virus is spreading.
- It’s tempting to piece those two elements together: If the virus is on the surfaces around us, and it also lasts for a long time in lab settings, naturally we should vigorously disinfect. But that doesn’t necessarily reflect what’s happening. In a study published in September in Clinical Microbiology and Infection, researchers in Israel tried to piece it all together. They conducted lab studies, leaving samples out for days on various surfaces, and found they could culture the remaining virus in tissue. In other words, it remained infectious. Then they gathered samples from highly contaminated environments: C19 isolation wards at a hospital, and at a hotel used for people in quarantine. The virus was abundant. But when they tried to culture those real-world samples, none were infectious. Later that month, researchers at an Italian hospital reported similar conclusions in The Lancet.
- In addition to environmental conditions, a confounding factor might be saliva, or the stuff that we often mean when we talk about droplets sticking onto surfaces. In her own research, Wyllie has studied how long certain viral proteins remain intact in saliva to help determine the reliability of C19 spit tests. For her purposes, stability is a good thing. But some proteins have appeared to denature more quickly than others, she notes, suggesting the virus as a whole does not remain intact and infectious. That could be because saliva tends to be less hospitable to pathogens than the synthetic substances or blood serums often used in lab-based stability studies.
- Consider, Wyllie says, the extraordinary chain of events that would need to happen to successfully spread SARS-CoV-2 on a surface. A sufficiently large amount of the virus would need to be sprayed by an infected person onto a surface. The surface would need to be the right kind of material, exposed to the right levels of light, temperature, and humidity so that the virus does not quickly degrade. Then the virus would need to be picked up—which you would most likely do with your hands. But the virus is vulnerable there. (“Enveloped” viruses like SARS-CoV-2 do not fare well on porous surfaces like skin and clothing.) And then it needs to find a way inside you—usually through your nose or your eye—in a concentration big enough to get past your mucosal defenses and establish itself in your cells. The risk, Wyllie concludes, is low. “I’ve not once washed my groceries or disinfected my bags or even thought twice about my mail,” she says.
- Low risk is not, of course, no risk, she adds. There are high-touch objects that merit disinfection, and places like hospitals need clean rooms and furniture. People at high risk from C19 may want to take extra precautions. But the best advice for breaking that object-to-nose chain, according to all the health experts I spoke with: Wash your hands.
- Goldman, too, had come to similar conclusions months before all this additional research came out, and US public health guidance followed right along with him. Since his Lancet paper in July, the focus on fomites has waned, and has been replaced by a focus on person-to-person transmission through respiration. The shift was based on epidemiological evidence. Experts knew all along that droplets passed by sneezing, coughing, or speaking were likely an important mode of transmission—that’s just how respiratory viruses tend to move. Over time, it became clear that aerosols, which remain suspended in the air, can better explain why so many infections seemed to be passing between people who did not directly interact, but could have shared the same indoor air. That’s why public health officials now emphasize mask wearing and ventilation. The CDC’s most recently updated guidance, from early October, holds that “spread from touching surfaces is not thought to be a common way that C19 spread.” For those reasons, or perhaps out of fatigue, the scrubbing became less scrupulous over the summer.
- But not for everyone. “I think that one thing that has been tough about this pandemic is there has been such a strong initial message that gave people the wrong intuition,” says Morris, the Princeton researcher. For some people, and especially for institutions that were trying to reopen, liable to employees and visitors, priorities had been set based on what we knew back in the spring. It was also a way to show that they were doing something, Morris adds, even if it didn’t do much. In July, The Atlantic’s Derek Thompson coined the term “hygiene theater” to describe the rash of corporate disinfection. It’s still around. It’s part of the reason why New York City has committed tens of millions of dollars to cleaning each subway car each night, why Airbnb requires “enhanced” cleaning from its landlords, why countless schools, stores, churches, and offices continue to emphasize disinfection. It’s why some libraries are quarantining books this fall for a week or more. It’s also a factor in what we are now less likely to do, a rationale for why many businesses no longer take cash and why playgrounds have often been among the last outdoor venues to reopen.
- “There are bizarre policies that haven’t changed or adapted,” says Julia Marcus, an epidemiologist at Harvard Medical School. “It’s one thing for an individual to decide to stop bleaching their groceries. It’s much more difficult to steer the ship of an institution as the science evolves, with different levels of decision making and different levels of health literacy and risk tolerance.”
- What is it about fomites? There’s surely something psychological in the belief that we can “see” an invisible virus, manifesting as an object that we can quarantine, avoid, wipe down. That’s evident in how we think about the research, even. Recall the salt shaker in Germany? Or the elevator buttons in a Chinese high-rise? In New Zealand, there was that hypothesis that containers of frozen fish were responsible for an outbreak there. Some of those conclusions can be attributed to aerosol starting off as a dirty, alarmist word. Public health officials were searching for something, anything, to explain why groups of people who didn’t gather closely were becoming infected.
- It’s impossible to rule out that some transmission could occur that way—and examples still come up, like a case in New Zealand possibly linked to a communal trash can—but most incidents now look like a case of shared air. Wyllie points to a friend who remains convinced they got the virus from a contaminated door handle. She thinks that’s unlikely, but for her friend, it’s an answer to a question of how they got sick that ambient virus floating in the air simply doesn’t offer. It’s a good story.
- Sharon Streams, director of the Realm project, says she sympathizes with that demand for answers. The group’s research on library materials was conceived after the surface research in March. At the time, the talk was all fomites, at the time. Library employees wanted specifics to better understand how the virus interacts with the billions of materials they handle each year, many of which are currently marooned in people’s homes, exposed to who knows what. “They’re pulling their hair out about what is the appropriate level of quarantine,” she says.
- Streams acknowledges that the conditions modeled in their experiments are based on a vague foundation. It’s hard to know whether the researchers started with a realistic dose of the virus, or whether the amount of it that remains on surfaces after a few days or hours would actually cause an infection. (The group’s latest research release, last week, included more language about aerosols and droplets being the likeliest modes of transmission.) But to her, that’s the point of gathering more data. And Streams points out that even if a weeklong quarantine looks like overkill to some virologists or health experts, quarantines and disinfection satisfy an emotional need that’s often overlooked. Much like the wiping down store shelves, church pews, or subway cars, cleaning policies are also about signaling which spaces are safe to come back to—that libraries are ready for visitors and employees. “‘Hygiene theater’ has been thrown around as a bad word, but they’re embracing it to show that we care about the people coming here,” she says. “They feel comforted.”
- But communicating that point is difficult. Marcus points back to the original paper on surface spread in March: “They couched it appropriately. But even with those caveats, it spun into a lot of obsessive behaviors,” she says. Even seemingly benign procedures, like quarantining items, can wear people out over time. “There’s such a high level of tension in our lives and decision making right now. We all need to feel some ease,” Marcus says. “For me, the question is, where are the low-risk areas where we can ease off the gas now that we know more about how transmission happens—which is overwhelmingly from being together in indoor environments? It’s not from a book that somebody sneezed on and brought to the library a week ago.”
- Worrying about the small stuff exhausts people from focusing on things that do matter. There are all sorts of ways to imagine what might go wrong. Maybe a person feels so confident in the disinfection methods around them that they eat indoors without a mask, despite the much more substantial known risks. Or perhaps someone feels they don’t need to quarantine themselves after traveling because they wore disposable gloves and booties over their shoes on the plane. “When you ask more of people than what is needed, they grow tired of doing what actually matters,” Marcus says. Her advice: Keep it simple.
- That sort of clear, simple guidance is hard to come by. Since The Lancet publication, Goldman has become a consultant and therapist of sorts for people who are questioning the utility of overly rigorous disinfection, but who are unsure of what to make of the scientific evidence. He’s been in touch with administrators at a local school that planned to close once a week for “a deep clean,” but who weren’t paying attention to their ventilation systems. He has fielded inquiries from people who still leave their groceries out for days, and who barely leave the house, encouraging them to find a healthier balance. He may be able to change minds one at a time, he reasons, or at least help people put the risks in perspective. It worked, he says, on his mother-in-law. But behaviors are hard to shift, especially when the decision is made by committee. The tendency, in the absence of firm guidance to do otherwise, is to cater to the most cautious.
- In Minnesota, Kalb, who is one of his acolytes, says her concerns about the pews, and the lack of evidence driving the deep cleaning, were carefully considered by the church reopening committee. But her fellow parishioners advised caution. The daily disinfection was part of a list of changes for safe reopening, including cordoning off rows for social distancing and a sign-up process to enable contact tracing. It was safest, the committee decided, to continue doing it all, much like every other nearby church and school and store was doing. After all, Kalb couldn’t point to a specific study that said fomite transmission was never happening. And there was news going around of an outbreak at a church in Texas. “It was like, OK, we don’t want to be that church,” she says. The church now uses a misting machine to spray disinfectant, which requires less active wiping.
- It’s tempting, in other words, to play it conservatively, says Berman, the librarian. “Some of it is just making sure the employees or the public feel safe,” she says, and she sees the benefits of disinfecting library surfaces that get a lot of use. But she points out that institutions have the power to alter our perception of safety, cutting through the ambiguity of risk by offering clear guidance. Holding out these scientific conclusions—the number of days the virus lasts on every imaginable type of library material surface—had done just the opposite, she believed, producing more fear than empowerment.
- Like so many decisions about risk and public safety in this pandemic, the burden had been displaced onto people like her, a librarian, not a virologist. She marveled at how much effort she was personally expending trying to educate herself and the people around her about the risk of books as fomites, when there was so much else to worry about. And, well, now she had done the research, and she knew the biggest risk in a library is the risk of sharing the same air, not touching the same book. Wouldn’t it be nice if someone with more authority would just come out and say so? “There’s so much fear out there,” she says. “I don’t want to put anyone at undue risk, but I want us to reopen.”
3. C19 — A Visual Library
- As C19 spread, Science’s journals began publishing a nonstop stream of research papers. Many explained critically important aspects of the disease and effects on human health. As senior scientific illustrator, I faced increased demands for rapidly created visuals that accurately conveyed information on new COVID developments.
- The graphic from the Perspective article “How does SARS-CoV-2 cause C19?” has been liked by more than 3,500 users on Instagram.
- As C19 spread, Science’s journals began publishing a nonstop stream of research papers. Many explained critically important aspects of the disease and effects on human health. As senior scientific illustrator, I faced increased demands for rapidly created visuals that accurately conveyed information on new COVID developments.
- Science’s COVID library contains the virus itself, its components, various cell receptors, cells, and our protagonist, the alveolus. The simple shared style allows elements to be easily reused and combined.
- Many COVID visuals depicted the same elements, such as the virus, receptors, or blood cells. To keep pace with the demand, I began saving and reusing these. Seeing this, Creative Director Beth Rakouskas suggested that I organize my COVID graphics into a library and create them all using a consistent visual style. Having this graphics library lets us spend more time working out accurate details with editors and authors rather than stressing about redrawing an alveolus.
- The common visual style also helped viewers recognize and identify with the Science brand of accurate visuals, whether they were seeing them in Science or outside the journal in social media. As the pandemic continues, public demand has soared for accurate and up-to-date graphics explaining the effects of this devastating disease. Science’s COVID graphics have been viewed nearly a quarter-million times on our social media accounts.
- Our library continues evolving as research reveals new findings. Here are some examples of how the graphics are used in different ways, helping keep both Science’s readers and the public well informed about the disease and its effects.
- The graphic from the Perspective article “How does SARS-CoV-2 cause C19?” has been liked by more than 3500 users on Instagram.
- These graphics illustrating the SARS-CoV-2 life cycle were published 2 months apart. Reusing elements allowed rapid creation of the newer graphic (right) while maintaining Science’s visual style. On the left, “Race to find C19 treatments accelerates.” On the right, “Rapid repurposing of drugs for C19.”
- The COVID library is used across the Science family of journals. Here, a Science Immunology graphic depicts how JAK kinase inhibitors are investigated as a way of managing cytokine storm in patients with severe C19.
- Blood vessel injury, above, may spur the disease’s fatal second phase. Interferon responses seen in viral pneumonias, right, focus on the alveolus.
- Above, versatile library graphics combine to create an illustrated table showing how fast cheap tests could enable a safer reopening.
- This large graphic communicated a lot of information about how the virus has potential to affect organs beyond the lungs. It was the first time that gross anatomy made its way into the picture and is a style-setter for how to do so. The unfussy style and modular design allowed for easier handling in our interactive version.
- Here, anatomy was illustrated to explain ongoing symptoms after a person has cleared the virus. While no library elements were used, we wanted it to act as a sequel to “An Invader’s Impact.”
- This graphic, from “Aging immunity may exacerbate C19,” was produced almost entirely from library elements.
K. New CDC Guidelines
1. CDC expands definition of close contact to include cumulative exposure
- The CDC on Wednesday expanded how it defines a “close contact” of someone with C19 as it released new evidence showing the coronavirus can be passed during relatively brief interactions.
- Previously, the CDC described a close contact as someone who spent 15 minutes or more within six feet of someone who was infectious. Now, the agency says it’s someone who spent a cumulative 15 minutes or more within six feet of someone who was infectious over 24 hours, even if the time isn’t consecutive, according to an agency spokesperson.
- Close contacts are those who are tracked down during contact tracing and are recommended to quarantine.
- The announcement from the CDC comes as scientists described in a new study how a correctional officer in Vermont appears to have contracted the coronavirus during “multiple brief encounters” with six incarcerated people who had C19. The infected people were awaiting the results of their C19 tests while the interactions happened.
- In the study, the authors — including officials from the CDC and Vermont’s health and corrections departments — noted that the data for defining a close contact have been limited. “A primary purpose of contact tracing is to identify persons with higher risk exposures and therefore higher probabilities of developing infection, which can guide decisions on quarantining and work restrictions,” they wrote, adding that “public health officials should consider transmission-risk implications of cumulative exposure time within such settings.”
- Experts have long noted that the 15-minute, within-six-feet rule was not some sort of threshold that needed to be hit for transmission to occur. So much about whether spread happens depends on how infectious a person is, how well-ventilated the room that people are in is, how the virus might move through the air in a particular setting, whether people are wearing masks, and more. The 15-minute window had just been used as a benchmark to prioritize who should be followed up with for contact tracing and quarantine.
- One reason why the length of interactions might matter, experts think, is because people need to be exposed to a certain level of virus if they’re going to get infected. Researchers still aren’t sure what that “infectious dose” is — and if a higher dose corresponds to how sick people are likely to get — but the thought is that the longer someone is around someone else who is infectious, the higher level of virus they will be subjected to, and the more likely they are to get C19.
- After the officer was diagnosed with C19 in August, health officials and staff at the correctional facility reviewed surveillance footage of his interactions with the six incarcerated people. Though he never spent 15 straight minutes within six feet of any one of them, he was within six feet of them at least 22 times during one eight-hour shift, cumulating in at least 17 minutes of exposure. During their interactions, the incarcerated people were wearing masks most, but not all, of the time, while the officer always had a microfiber cloth mask, gown, and eye protection on.
- The correctional officer had no known contact with anyone else with C19 and coronavirus cases were low in his home county and in the rest of the correctional facility at the time, leading researchers to rule that his case most likely came over the brief encounters.
- The new study “adds to the scientific knowledge of the risk to contacts of those with C19 and highlights again the importance of wearing face masks to prevent transmission,” the CDC spokesperson said.
M. Johns Hopkins COVID-19 Update
October 21, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 39.94 million cases and 1.11 million deaths as of 8:00am EDT on October 19. The WHO reported a new record high for global weekly incidence for the fifth consecutive week. The global total reached 2.44 million cases—an increase of more than 5% over the previous week. Additionally, the WHO reported 394,510 new cases on Saturday, a new daily record.
- Total Daily Incidence (change in average incidence; change in rank, if applicable)
- Per Capita Daily Incidence (change in average incidence; change in rank, if applicable)
- Considering the current C19 resurgence in the US, India is unlikely to surpass the US as #1 for cumulative incidence in the near future. India is still reporting more new daily cases than the US; however, India continues its decline, while US daily incidence is increasing again.
- Colombia and Mexico fell out of the top 10 in terms of total daily incidence, and they were replaced by the Czech Republic and Italy. Notably, Italy’s daily incidence doubled over the past week, and the daily incidence increased by more than 60% in the Czech Republic. France’s daily incidence has doubled over the past 2 weeks. The Bahamas, Iceland, and Israel fell out of the top 10 in terms of per capita daily incidence, and they were replaced by Armenia, Liechtenstein, and Slovenia. Belgium, which was not in the top 10 per capita daily incidence two weeks ago, has jumped to #3 globally. Armenia’s daily incidence increased by 108% compared to the previous week, Slovenia’s increased by 132%, and Liechtenstein’s increased by 617%.
- The US CDC reported 8.08 million total cases and 218,511 deaths. The daily C19 incidence continues to increase, now up to 55,323 new cases per day, the highest since August 5. On Saturday (data corresponding to October 16), the CDC reported 70,078 new cases, the highest daily incidence since July 24 and the sixth highest daily total to date. The US C19 mortality continues to hold steady at approximately 700 deaths per day.
- The US surpassed 8 million cumulative cases. From the first case reported in the US on January 22, it took 96 days to reach 1 million cases. From there:
- 1 million to 2 million: 44 days
- 2 million to 3 million: 27 days
- 3 million to 4 million: 15 days
- 4 million to 5 million: 17 days
- 5 million to 6 million: 22 days
- 6 million to 7 million: 25 days
- 7 million to 8 million: 21 days
- More than half of all US states have reported more than 100,000 cases, including 10 with more than 200,000 cases:
- The Johns Hopkins CSSE dashboard reported 8.17 million US cases and 219,811 deaths as of 12:30pm EDT on October 19.
2. US HOSPITAL SURGE
- As much of the US continues to face another resurgence of C19, rural hospitals are struggling to manage the patient demand. The US C19 epidemic, which was largely concentrated in higher-density urban populations early on (eg, New York City, Boston, Detroit), has shifted toward rural populations across the country. In fact, the per capita C19 mortality in small towns and rural areas is now more than double the mortality in large cities. Unlike urban areas, which may have many nearby hospitals to provide care for their large populations, and to distribute increased patient load, hospitals and other healthcare facilities in rural areas are spread further apart, covering much larger geographic areas. In some cases, the nearest hospital may be hundreds of miles away. Additionally, these hospitals tend to be smaller than their urban counterparts, and the associated limitations on resources, including hospital and intensive care unit (ICU) beds, increase the burden of C19 patient surges. As we covered early in the pandemic, a growing number of rural hospitals in the US have closed their doors over the past several years, and restrictions on elective procedures during the height of social distancing measures in the US placed additional economic stress on hospitals and health systems, causing more to close.
- In an effort to decompress patients from overburdened health systems (ie, transfer them to other facilities), Wisconsin established a temporary field hospital at its state fairgrounds. The facility opened last week, and it will initially be able to accommodate up to 50 patients. It is designed to provide care for patients who are recovering from C19 but who are not yet ready to be discharged. More severe patients will remain at traditional hospitals to receive more advanced clinical care. Ultimately, the field hospital could be expanded to handle more than 500 patients, if necessary. Wisconsin currently has more than 1,000 hospitalized C19 patients statewide, its highest total to date.
3. SWEDEN SOCIAL DISTANCING
- Since early in the C19 pandemic, Sweden has largely resisted highly restrictive social distancing and other mitigation measures to limit SARS-CoV-2 transmission. Unlike most other European countries, Sweden placed few restrictions on retail stores, restaurants and bars, or schools. The reluctance to implement widespread social distancing policies has resulted in numerous accusations from the international community that Sweden is pursuing a herd immunity strategy through natural infection—Swedish officials have denied that herd immunity is the goal. In light of increased incidence during Europe’s “second wave,” Swedish officials are reportedly evaluating plans to implement local social distancing restrictions in severely affected areas.
- Dr. Anders Tegnell—Sweden’s leading epidemiologist, who received the brunt of opposition to Sweden’s perceived herd immunity strategy—recently commented that the seroprevalence in the population was not as high as previously believed, which likely factors into Sweden’s evolving mindset. It appears as though the new policies will still largely be recommendations, as opposed to mandates, and they will be implemented locally not at the national level. While these measures are not nationwide mandates, it appears that Sweden’s overall strategy toward containing C19 is moving closer to the model implemented across the rest of Europe. On October 13, Sweden reported 970 new cases, its highest daily total since late June.
4. VATICAN/HOLY SEE
- When reporting the per capita daily incidence top 10, we typically omit small countries that normally report zero daily cases but occasionally report a minor, temporary spike in incidence in favor of countries that exhibit a trend of elevated incidence. This week, the Vatican/Holy See reported 7 new cases twice, which would put it at #1 globally in terms of per capita incidence, at nearly 2,500 daily cases per million population.
- At least 11 of the 14 new C19 cases are among the Swiss Guard, who provide security for the Pope. Additionally, a man who lives “in the same Vatican residence as Pope Francis” tested positive for SARS-CoV-2. Pope Francis is 83 years old, and he reportedly “had part of one lung removed during an illness when he was a young man,” which could further increase his risk for severe C19 disease. The Pope undergoes regular testing, and there is no indication that he has been directly exposed to any infectious individuals. These are the first cases reported by the Vatican/Holy See since mid-March—and more than doubled the country’s cumulative total—but considering that both reports included multiple cases and that most of the cases were among a small group of individuals, it is worth monitoring for early signs of sustained transmission.
5. LITHUANIA ELECTION
- Lithuania updated its policies regarding C19 isolation and quarantine to provide an exemption that would allow quarantined citizens to vote during the upcoming elections. Under the new policy, individuals who have exposure to known C19 cases but who have not tested positive are permitted to leave quarantine to participate in a limited window of early voting, October 19-22 from 7-8pm only. Voters must be transported to the polling station in their own car, wear a face covering while voting, and then return directly home. Reportedly, 4 polling stations have set up drive-through ballot drop-off. Individuals with active C19 disease are not permitted to participate in early voting, but they can “vote from home,” presumably by mail. According to a report by the Associated Press, Lithuania did not offer an option for quarantined individuals to vote in person during the previous round of the national election.
6. WHO SOLIDARITY TRIAL
- week, the WHO published preliminary results from the Solidarity Therapeutics Trial, the world’s largest randomized controlled trial evaluating candidate C19 treatment drugs. Despite high hopes, the findings indicated that remdesivir, hydroxychloroquine, lopinavir/ritonavir, and interferon—all of which are repurposed drugs—had “little or no effect on…mortality or the in-hospital course of C19 among hospitalized patients.”
- Physicians and researchers have expressed mixed reviews of the trial, however, including criticism of the study design and inconsistency between the Solidarity Trial’s results and other major clinical trials, particularly for remdesivir.
- Notably, Gilead Sciences, the company that produces remdesivir, issued a press release that leveled criticism against the WHO’s findings. In particular, Gilead argued that while the international, multi-center nature of the Solidarity Trial increased availability of the drugs, it also introduced heterogeneity that could call into question the validity of the results. Additionally, Gilead noted that the data had not yet been peer reviewed. Solidarity Trial researchers submitted a manuscript discussing the Solidarity Trial data for peer review, but a preprint version is available here.
7. VACCINE ROLLOUT
- Despite Pfizer’s recent announcement that it would not seek an Emergency Use Authorization (EUA) from the US FDA before late November, US government planning continues for the future rollout of a C19 vaccine. Last Friday marked the deadline for US states to submit preliminary plans to the US CDC regarding future vaccine distribution programs. The CDC released its own guidance for state planning in mid-September. The US Department of Health and Human Services and the Department of Defense also recently announced an agreement with the CVS and Walgreens pharmacy chains to vaccinate residents and staff of nursing homes and long-term care facilities, once a vaccine is available, at zero out-of-pocket cost for recipients. CVS and Walgreens will also manage storage of the vaccine and related supplies as well as reporting vaccination data to local, state, and federal officials. Long-term care facilities will not be mandated to participate in the mass vaccination program, but they can opt in via the CDC’s National Healthcare Safety Network.
- This planning comes at a time when polls show Americans are increasingly hesitant to receive a SARS-CoV-2 vaccine. In fact, a recent poll conducted by STAT News and The Harris Poll found that only 58% of Americans indicated that they would receive a vaccination as soon as it was available. This is down from 69% in August. Among Black Americans, only 43% of individuals stated they would receive a vaccination as soon as it was available—down from 65% in August—further illustrating challenges in encouraging vaccination among racial and ethnic minority communities. Rob Jekielek, Managing Director of The Harris Poll, indicated that Black individuals are more likely to live more than 1 hour away from a primary care physician and more likely to use a hospital emergency department as their point of entry into the healthcare system. T As we have covered previously, racial and ethnic minorities have been demonstrated to be at elevated risk for severe C19 disease and death, so it is critical to engage these communities prior to the availability of a SARS-CoV-2 vaccine in order to increase vaccination coverage among vulnerable individuals.
- Outside of the US, similar preparation work is also being done. UNICEF, Gavi, and the WHO recently partnered to stockpile supplies and equipment needed for future vaccine distribution, such as syringes, safe syringe disposal boxes, and cold chain equipment. Notably, UNICEF announced that it is working to stockpile more than half a billion syringes by the end of 2020.
- Emerging reports indicate that C19 patients may develop new-onset diabetes or experience complications to pre-existing diabetes as a result of SARS-CoV-2 infection. Diabetes has already been documented as one of the underlying health conditions that can increase the risk of severe C19 disease and death, but it appears as though the association could work the opposite way as well—with C19 actually causing patients to develop diabetes. Current hypotheses indicate that the complication may be related to SARS-CoV-2 binding to ACE2 receptors, which also play a part in regulating glucose metabolism.
- The onset of type 1 diabetes has been linked in the past to other viral infections, which may cause stress that raises blood sugar levels; however, new-onset diabetes in those circumstances typically only occurs in patients who are already predisposed to developing diabetes. Conversely, new-onset diabetes in C19 patients has been observed in patients that do not have risk factors for diabetes. Further, some hospitals have reported unusually high rates of pediatric diabetes and patients presenting with diabetic ketoacidosis—a complication of diabetes—during the pandemic.
- In order to further research this phenomenon, doctors and researchers from King’s College London and Monash University (Australia) are establishing an international registry of C19-related diabetes cases. More than 300 physicians have already agreed to participate by sharing clinical case data. The US National Institutes of Health is also funding research exploring the link between C19 and new-onset diabetes or high blood glucose.
- Previous studies have evaluated genetic risk factors for severe C19, including a potential link between severe outcomes and blood type, but a new study published in the The New England Journal of Medicine may provide further evidence of genetic risk factors for C19. The genomewide association study (GWAS), conducted by the Severe C19 GWAS Group, involved 1,980 severe C19 patients from 7 hospitals in Italy and Spain.
- The researchers found that the ABO blood group locus at 9q34.2 and the multigene locus at 3p21.31 were associated with severe C19 outcomes. Consistent with other research, the findings suggest that patients with blood type A had a higher risk of severe outcomes and that patients with blood type O had a lower risk of severe outcomes. An insertion-deletion GA or G variation at locus 3p21.31 was specifically linked to patients requiring mechanical ventilation. Due to limitations in the methodology, the researchers were not able to test and adjust for some potential sources of bias known to be associated with C19, and further study is needed to better characterize the identified relationships. Regardless, the study identified potential areas of focus for future genomic research, and the researchers call for future efforts to further investigate the immunologic synapse between T-cells and antigen-presenting cells.