November 17, 2020
Without reliable information, we rely on fear or luck.
Moderna C19 vaccine 94.5% effective in trial
“Obviously, with 90 plus percent effective vaccine, you could feel much more confident, but I would recommend to people to not abandon all public health measures such as masks and social distancing just because you’ve been vaccinated.”Dr. Fauci
“Suddenly the fate of this country lay in our hands. So, we mustered all our courage and did what was expected of us, the only right thing. We did nothing. Absolutely nothing. Being as lazy as raccoons. Days and nights, we stayed on our asses at home and fought against the spread of the coronavirus. Our couch was the front line and our patience was our weapon.”German public relations campaign praising “heroes” of the pandemic
“It’s not clear what will stop this exponential growth in new cases. The containment measures taken thus far have been very localized and limited. Unlike in the summer, the rise in cases does not seem to have prompted much change in individual behavior. It will take longer for local officials to respond to the current surge because the virus is spread across the country and only a few places are currently running out of hospital capacity. And governors across the US are understandably hesitating to reimpose strict restrictions.”Bank of America analysis
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
K. Linked Stories
- 38% of Americans planning on having Thanksgiving dinner with 10 or more people
- New saliva-based antibody test for the coronavirus highly accurate in initial study
- Sleep apnea may be risk factor for C19
- Will the C19 Evolve to Be Less Deadly?
- MIT Chemists Discover the Structure of a Key Coronavirus Protein
- Benefits of high-dose blood thinners in C19 patients remain unclear
- COVID Virus Transmission From Human to Mink, As Well as From Mink to Human Revealed by Whole Genome Sequencing
- Hydroxychloroquine does not help patients hospitalized with C19
- With or without allergies, outcomes similar for hospitalized patients with C19
- How to Make Buildings Breathe Better
- Run-It-Hot Wins Argument Over How to Get Americans Back to Work
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A. The Pandemic As Seen Through Headlines
(In no particular order)
- Dr. Fauci calls Moderna COVID-19 vaccine ‘quite impressive’
- Johnson & Johnson launches late-stage trial for COVID-19 vaccine
- Pfizer-BioNTech vaccine creator says life could return to ‘normal’ next winter
- BioNTech CEO says vaccine shipments to start in early January
- HHS’s Azar: We hope to vaccinate 20M against COVID-19 in December
- CDC panel to decide who gets COVID-19 vaccine first
- States Vow Extra Scrutiny of Coronavirus Vaccine
- Missing From State Plans to Distribute the Coronavirus Vaccine: Money to Do It
- Only 46% Of Americans Would Receive COVID Vaccine As Soon As It Is Available
- 67% of Americans are concerned about vaccine side-effects
- State media claims China’s COVID-19 vaccine is 90 percent effective
- Pfizer COVID-19 vaccine spurs wave of freezer panic buying across country
- Biden COVID Advisory Board Member: Consensus of Board ‘Is That We Do Not Need’ Lockdowns We Had in Spring
- WHO uncovers COVID-19 cluster at its own headquarters in Switzerland
- Israel In Talks To Buy Russia’s COVID Vaccine
- Michigan halts classes, indoor dining as coronavirus surges
- Washington Governor Orders Sweeping New Lockdown Restrictions
- Oregon, New Mexico order lockdowns, as coronavirus cases surge across US
- New Jersey to tighten limits on gatherings amid COVID-19 surge
- California reimposes restrictions statewide
- Philadelphia to shut down indoor dining, gyms and museums amid COVID-19 surge
- Workers worry about losing wages as States take tough steps
- Pandemic pressures are driving thousands of doctors and nurses out of the medical profession
- Doctors plead with Americans to take the virus surge seriously
- Thousands of medical practices in the U.S. are closing, as health care workers decide to retire early or shift to less intense jobs
- With 11 Million Cases in the U.S., the Coronavirus Has Gotten Personal for Most People
- More than 1 million US kids have had COVID-19
- 70% Of Americans Unlikely To Travel For Holidays As US Faces Second Virus Wave
- Texas surged past 20,000 COVID-19 fatalities, giving it the second-highest death toll in the nation after New York
- In the Minnesota section of the The Minneapolis Star-Tribune on Sunday, two-thirds of the 16 pages were filled with obituaries
- The Navajo Nation reinstated a stay-at-home order for the next 3 weeks after health officials warned of “uncontrolled spread” of the virus across the vast reservation
- Sweden will reduce the limit on public gatherings to 8 people from 300, as part of a new approach that runs counter to the country’s previously lax virus restrictions
- India will fly doctors into the region around New Delhi, double the number of tests it carries out and ensure that people wear masks, in an effort to contain the spread of coronavirus
- Illinois reports another 11,000+ new cases
- Germany imposes new restrictions next week
- UK reports 21,000+ new cases
- NYC hospitalizations hit new high
- NYC positivity rate has climbed to 2.77%
- NY cases top 3,600, highest since the spring
- NJ sees 2nd straight COVID record
- NYC schools to stay open
- NYC parents resisting public school closures as COVID-19 surges
- US suffers 10th day of 100,000+ new cases
- 38 states report 1,000+ new cases
- Austria orders mandatory COVID tests
- Italy calls in warzone doctor over COVID-19 health crisis
- Germans will live with “considerable restrictions” for months
- Tokyo reports another 350+ new cases as Japan’s outbreak worsens
- NJ lowers limit on private indoor gatherings
- More states tighten restrictions
- Merkel urges more restrictions on private gatherings
- Mexico passed 1 million cases
- Hungary reported a record jump in cases
- Iran sees new record in cases
- South Korea reports most new cases in 11 weeks
- New York City’s public schools remain open, for now
- More New York sheriffs say they won’t enforce Cuomo’s Thanksgiving edict
- New COVID-19 cases and deaths rise sharply in France
- Mexico surpasses one million coronavirus cases
- Researchers find coronavirus was circulating in Italy earlier than thought
- Water cannon fired at Frankfurt anti-lockdown rally
- Kenyan Doctors Threaten Strike as Virus Infections, Deaths Surge
- ‘Can’t take any more’: Lisbon’s bar, restaurant workers protest amid COVID-19 rules
- Paris boulevards deserted as lockdown claims Christmas shopping trade
- UN food agency warns 2021 will be worse than 2020
- The NFL says none of its 200 virus cases in the first half of the season were linked to games
- The N.C.A.A. will hold its men’s basketball tournament in just one city in 2021, citing pandemic concerns
- French Catholics hold open air mass to protest COVID-19 restrictions
- Oregon official vows to defy COVID-19 order limiting Thanksgiving gatherings
- New stats reveal massive NYC exodus amid coronavirus, crime
- Seven test positive for COVID-19 on first Caribbean cruise since March
- California Gov. Gavin Newsom apologizes for breaking own COVID-19 rules
- Virus-Delayed Tokyo Olympics Looks to Allow Spectators
- President-elect Joe Biden warned of a “very dark winter” ahead and called on Congress to pass an economic stimulus package immediately
- New York City’s tourism industry will need at least four years to recover from the free-fall prompted by the pandemic
- Lockdowns Haven’t Brought Down COVID Mortality, But They Have Killed Millions Of Jobs
- Mass Tourism Will Be Roaring Back by Summer, Says Expedia CEO
- 38% of Americans planning a big Thanksgiving despite COVID-19
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 = 55,341,406
- New Cases = 504,567
- New Cases (7 day average) = 581,907
- Growth rate in 7 day average has slowed significantly during the last week
- 1,000,000 new cases every 1.7 days (based on 7 day average)
US Cases & Testing:
- Total Cases = 11,538,057
- New Cases = 162,149
- New Cases (7 day average) = 158,332
- Percentage of New Global Cases = 31.4%
- Total Number of Tests = 170,136,004
- Percentage of positive tests (7 day average) = 12%
- Record high 7 day average of new cases
- 7 day average of new cases are increasing at a very high rate
- During the last 30 days, the 7 day average has increased from 56,852 to 158,332, an increase of 178.5%
- 7 day average is 392.6% higher than on 1st peak (4/11)
- During the last 30 days, the 7 day average of the percentage of positive tests has increased from 6.1% to 12%, an increase of 96.7%
- Total Deaths = 1,331,751
- New Deaths = 7,305
- New Deaths (7 day average) = 8,896
- Record high 7 day average of new deaths
- 7 day average is increasing at a rapid rate
- During the last 30 days, the 7 day average has increased from 5,274 to 8,896, an increase of 68.7%
- Total Deaths = 252,651
- New Deaths = 739
- New Deaths (7 day average) = 1,170
- Percentage of Global New Deaths = 13.2%
- 7 day average of new deaths have been steadily increasing over last 30 days
- During the last 30 days, the 7 day average has increased from 706 to 1,170, an increase of 65.7%, which is amount the same rate of increase as the worldwide 7 day average
- The 7 day average of new cases is increasing at a rate of 171.7% faster than the 7 day average of new deaths
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (11/16)
- The positivity rate continues to surge across the country
- Nationally, the average 7-day positivity rate was 12.0% — up from 8.1% as of 11/2.
- More than 62% of all tests are now positive in ND (down from 68% on 11/12), 57% in SD, and 53% in IA
- Two states (MT and NE) 7-day positivity rates greater than 40%.
- Six states (ID, WY, WI, IN, NV, MN) 7-day positivity rates greater than 30%.
- Six states (RI, UT, MO, CO, PA, KS) had 7-day positivity rates greater than 20%.
- In total, 44 states have 7-day positivity rates greater than 5% (+3 states since 11/12)
- Hospitalizations in the US surge to 73,014, up 50.6% since 11/2.
- 48 states have had increases of hospitalized patients of more than 10% since 11/2
- 24 states have more than 1,000 hospitalized patients
- All states are seeing an increase in hospitalizations. Only HI and SC have seen increases less than 10% since 11/2
- ICU Patients in the US rise to 14,313, up 45.2% since 11/2.
- 32 states have seen the number of ICU patients increase by more than 10% since 11/2
- 28 states have more than 100 patients in ICU, (+3 states since 11/2)
- Only RI saw a decrease in the number of ICU patients since 11/2
4. Covid Is Resurging, and This Time It’s Everywhere
- With a third surge of the C19 pandemic hitting the U.S., many public-health authorities are warning the coronavirus is now so widespread that it will take pervasive new measures to contain it.
- New infections surpassed 177,224 on Friday, setting a daily record that eclipsed the highest daily case counts of previous peaks in the spring and summer. The number of new infections was lower Saturday at 166,555, while new deaths numbered nearly 1,300, according to data compiled by Johns Hopkins University. The number of people hospitalized with C19, meanwhile, reached 69,455 on Saturday, according to the Covid Tracking Project.
- In earlier surges, infections were concentrated in cities such as New York and Chicago, or populous states like Florida and Texas. Many of the outbreaks then were linked to travelers returning from overseas or so-called superspreading events such as conferences, weddings and rallies.
- Now, it is everywhere. People are becoming infected not just at big gatherings, but when they let their guard down, such as by not wearing a mask, while going about their daily routines or in smaller social settings that they thought of as safe—often among their own families or trusted friends.
- The number of confirmed cases is rising significantly in all but a few states, according to a Wall Street Journal analysis of data from Johns Hopkins University. Most of the new cases are in the Midwest, which is experiencing a major surge. But even states and cities that had successfully beaten the virus down to low levels are struggling with rising numbers of illnesses.
- “This is clearly a nationwide event,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, who is a member of President-elect Joe Biden’s C19 advisory board for the transition. “We have many mini-epidemics.”
- The number of hospitalizations has reached a new high, though hospital stays are shorter and fewer people are dying than in the spring, likely due to more medical knowledge and better treatment. The seven-day average of new daily C19 deaths in the U.S. was above 1,000 last week. But that average was still well below the highs seen in April when the seven-day average briefly topped 2,200 daily deaths.
- Disease modelers predict a difficult winter ahead, as families and friends gather; just how difficult will depend on the measures that authorities, businesses and individuals take now to slow the virus, public-health experts say.
- Some state officials took new steps last week, including stricter mask mandates and tighter restrictions on gatherings. In Wisconsin and Chicago, officials issued stay-at-home advisories, while Vermont’s governor prohibited all public and private social gatherings outside of members of the same household.
- Total shutdowns may not be necessary, said Celine Gounder, an infectious-diseases specialist and epidemiologist at NYU Grossman School of Medicine and Bellevue Hospital. Enough has been learned about the virus over the past many months that interventions can be more targeted to certain ZIP Codes or types of gathering places, more like a dimmer than an on-off light switch, she said. “I think at this point we actually know enough—we’ve learned a lot—that we’re not going to have to be quite so draconian in our measures,” said Dr. Gounder, who is also on the C19 transition advisory board.
- Many state and local leaders have been reluctant to return to the broad lockdowns imposed in the spring, in large part because of the severe economic and financial consequences for businesses and the public. The pandemic has already cost millions of jobs in the U.S. alone and dented global output.
- Epidemiologists cite several factors behind the current surge: colder weather driving people indoors, including into bars and restaurants; the return of students to college campuses; public-health measures such as mask-wearing that are recommended but not required in some states; mixed messages about the dangers of the virus; and pandemic fatigue.
On Halloween, Zachary Mathes and Sarah Katz invited two friends from their “social bubble” over to watch trick-or-treaters, sitting socially distanced outside their Pittsburgh home. Vigilant for months about protecting themselves from the virus, they thought the small gathering was low-risk.
When it got cold outside, the four went to warm up and eat some snacks in the kitchen, leaving masks off after discussing the move first. “We kind of decided we’re all OK; that is our friend group that we are a part of,” said Ms. Katz.
- Days later, they learned the guests had tested positive for C19. By then Ms. Katz, a 27-year-old communications specialist, and Mr. Mathes, a 29-year-old musician, had symptoms too.
- “We thought we were doing everything right, but we still got sick,” said Ms. Katz, who is riding out the illness at home with her husband.
- The virus, having spread for months, is now more entrenched in communities, epidemiologists say.
- “When you have so many cases in the community, it is very easy to get infected inadvertently as you go about your daily business,” said Ali Khan, a veteran epidemiologist who is dean of the College of Public Health at the University of Nebraska Medical Center. “You don’t need to go to hot spots anymore.”
C. New Scientific Findings & Research
1. Lower Temperatures Means More Cases
- In a recent note to clients, a team of researchers at Goldman Sachs took a close look at temperatures and studied whether there was a correlation with temperatures. Perhaps unsurprisingly, the team found a strong negative correlation between confirmed cases and temperature, with the number of confirmed cases going up while the temperature goes down.
- As the regression modeled by Goldman shows, the further temperatures drop with a modest lag between the summer and the winter, the more extreme the surge in C19 cases. This applies in both the US and Europe.
- Using fixed effects modeling, the Goldman team then tried to strip out other factors to try and isolate and expose the influence of temperature on case growth.
- Interestingly enough, the analysts analysis found that no matter the difference in statewide policies and enforcement, cases appeared to wax and wane along with changes in temperature, appearing to resist most efforts to control the virus.
- This notion isn’t all that surprising. Most other coronaviruses (i.e., the common cold), along with various influenza strains, are heavily influenced by temperature and seasonal effects (hence “flu season”).
- Medical literature cited by Goldman explains the seasonality trend in two key ways: Increase indoor social activity for “hosts”, which increases exposure, along with the cold weather’s impact on the immune system and general health (making individuals more vulnerable).
- Armed with these models, Goldman’s team of analysts produced a set of projections showing that the economies of the US and Europe will likely slow significantly during Q1 and Q4, followed by a springtime thaw as new case numbers start to recede.
2. Cytokine storms play a limited role in moderate-to-severe C19
- Rather than life-threatening hyperinflammation, most adults with moderate-to-severe C19 have a suppressed viral immune response when compared to adults with another viral respiratory infection, influenza. St. Jude Children’s Research Hospital and Washington University School of Medicine in St. Louis led research that suggests most C19 patients are not candidates for treatment with steroids such as dexamethasone. The research appears today in Science Advances.
- Fewer than 5% of the C19 patients in this study, including some of the sickest individuals, had the life-threatening, hyperinflammatory immune response known as cytokine storm syndrome. Cytokines are small proteins secreted by blood cells that help coordinate the immune response and trigger inflammation. Cytokine storms develop when excess or abnormally regulated cytokine production leads to hyperinflammation and tissue damage. While dexamethasone and other steroids are prescribed to treat cytokine storms, the drugs can backfire in patients whose immune response is already suppressed.
- Cytokine storms have been proposed as the cause of respiratory failure in C19 patients.
- “We did identify a subset of C19 patients with the broadly upregulated array of cytokines, which is a hallmark of cytokine storm,” said co-corresponding author Paul Thomas, Ph.D., of the St. Jude Department of Immunology. “But, overall, the average person with C19–even patients with moderate-to-severe disease–had less inflammation than the average person with flu.
- “The findings suggest that treatment suppressing inflammation might only be effective in that minority of patients with the hyperinflammatory profile,” Thomas said. He, Ali Ellebedy, Ph.D., and Philip Mudd, M.D., Ph.D., of Washington University School of Medicine, are corresponding authors of the study.
- What’s needed, researchers said, is a fast, reliable and inexpensive test to measure cytokines and identify patients who are most likely to benefit from immunosuppressive treatment.
- “Current clinical studies do not adequately target these therapies to the patients who many benefit the most,” said Mudd, a scientist and emergency medicine physician who treats patients with C19 at Barnes-Jewish Hospital in St. Louis. “Directing immunosuppressive therapies to the small subset of C19 patients who have an overactive immune response is the only way to know if these approaches are ultimately helpful.”
Immune responses: C19 vs flu
- What’s also needed is a better understanding of the immune response to C19, including the cause of respiratory failure that has been reported in as many as 8% of patients.
- Researchers sought to do that in this report, which stems from one of the largest and most comprehensive comparisons yet of the human immune response to flu and coronavirus (SARS-CoV-2). Unlike C19, the immune response to flu has been studied for decades and is better understood.
- The research included 168 adults with C19, 26 adults with flu and 16 healthy volunteers. More than 90% of the C19 patients were hospitalized, about half in the intensive care unit. Twenty-three percent of those hospitalized died. More than half of flu patients were hospitalized, 35% in the ICU, and 8% of those hospitalized died.
- To understand the immune response, researchers measured a variety of immune cells and factors, including 35 different cytokines. Seven C19 patients, or 4%, met the study definition of cytokine storm, meaning that about half or more of the 35 cytokines were significantly elevated compared to patient averages. Statistically, the elevation was defined as at least two standard deviations above the mean.
- Patients with cytokine storm syndrome had individual cytokine levels as much as 10- to 100-times higher than the average. But when researchers included age and other factors, C19 patients had lower overall cytokine levels than flu patients.
If not cytokine storm, what?
- “The lack of hyperinflammation in most C19 patients does not mean they had less disease,” said co-first author Jeremy Chase Crawford, Ph.D., of St. Jude Immunology. “We are saying that in most cases the disease was not caused by broad hyperinflammation from cytokine storm, which has important implications for developing generalizable C19 therapeutics.”
- The analysis revealed that the antiviral immune response was profoundly suppressed in C19 patients compared to flu patients. Along with measuring cytokines, researchers analyzed cytokine transcription in individual blood cells in patients with flu, C19 and healthy volunteers. C19 was associated with significantly reduced production of and response to Type I and Type II interferons, cytokines that play a central role in the antiviral immune response.
- Researchers also found evidence that SARS-CoV-2 alters pathways controlling the immune response to promote steroid production by patients.
- “Our results suggest that most C19 patients are perhaps already producing high levels of glucocorticoids prior to treatment, possibly leading to the blunted immunity we see in most of them,” Thomas said. “These patients may need therapy to turn up their immune response to knock the virus down.”
3. Antibody evolution may predict C19 outcomes
- For C19, the difference between surviving and not surviving severe disease may be due to the quality, not the quantity, of the patients’ antibody development and response, suggests a new Cell paper published by Galit Alter, PhD, a member of the Ragon Institute of MGH, MIT and Harvard.
- The study, published in the journal Cell, used Alter’s systems serology approach to profile the antibody immune responses of 193 hospitalized C19 patients, comparing responses from patients with moderate and severe disease and patients who passed away from C19.
- While all patients developed antibodies against the coronavirus (SARS-CoV-2), the way the antibodies developed, or evolved, differed between the three groups. For patients that didn’t survive the disease, the antibody response never fully evolved.
- “There was a significant defect in the development of IgG antibodies, which may be essential in the early control and elimination of the virus, ” Alter says. “Here, we were able to see the global impact of this defective IgG evolution, resulting in a compromised ability to promote essential viral clearing immune functions.”
- In a mature immune response, antibodies both block infection and direct the immune system to kill infected cells. To guide the killer immune response, antibodies attach to the Fc-receptor, a “docking site” specific to antibodies that is found on all immune cells. Without strong Fc-receptor binding, antibodies may fail to grab and destroy virus following infection.
- Compared to survivors, patients who passed from C19 had antibodies that never fully developed the ability to strongly bind to Fc-receptors and therefore may not have been able to fully trigger immune killing activity.
- Alter’s group, led by Tomer Zohar, Carolin Loos, Stephanie Fischinger, and Caroline Atyeo, PhD, also found that survivors’ immune systems could recognize and target an area of the SARS-CoV-2 spike protein known as the S2-domain. The S2 domain is found in other coronaviruses that infect humans, so patients whose antibodies can target it may have pre-existing immunity to the S2 domain because of exposure to other, common coronaviruses.
- Patients with antibodies that can recognize S2 domains on different coronaviruses may be able to use this pre-existing immunity to generate killer antibodies faster and sooner following SARS-CoV-2 infection.
- “If we can further understand the importance of cross-coronavirus immunity,” says Zohar, “researchers may be able to design vaccines able to counteract a much broader range of coronaviruses.”
- With studies like these, Alter and her team are working to understand the nature of protective immunity against SARS-CoV-2, including partnering with C19 vaccine developers, to help bring an end to this pandemic.
4. Shutting Down C19 virus’ destructive proteins with aerosolized molecules
- Researchers at Georgetown University Medical Center have successfully used molecules comprised of small strands of RNA to shut down the production of destructive proteins generated by the C19 virus. Additionally, the researchers are working to aerosolize the RNA molecules so that they could be incorporated in an inhalable drug that would mitigate viral chaos. The finding appears online today in Gene Therapy.
- A key to the Georgetown research efforts was the use of either microRNA (miRNA) or silencing RNA (siRNA, also known as small interfering RNA), both of which are RNA molecules. These molecules can guide the ultimate expression of how protein production occurs in a virus. And it is the proteins produced by the coronavirus (SARS-CoV-2) that wreak havoc in people.
- SARS-CoV-2 bears biological similarities to other respiratory viruses, such as the seasonal flu. The use of Tamiflu® (oseltamivir) to treat and prevent infection from the flu has proved to be helpful in lessening flu symptoms and its lethality in some people.
- “We believe that our approach suppresses viral protein production and could be used against virtually any respiratory virus,” says G. Ian Gallicano, PhD, associate professor in the Department Biochemistry and Molecular and Cellular Biology at Georgetown University Medical Center. “Because of our results, Georgetown University has filed a patent application on on the siRNA sequences that were shown to have the best effect on viral protein suppression.”
- Another key to the researcher’s effort was the fact that miRNAs and siRNAs can be made fat-soluble, making them more easily absorbed using sprays into nasal passages lined with mucous membranes. Non-soluble fat compounds have been found to irritate nasal passages if inhaled.
- While Tamiflu is a pill that can help control the flu, the Georgetown researchers’ proposed drug has a tougher disease to try to control and thus its mechanism of action would be different. An aerosolized RNA-targeting agent against SARS-CoV-2 would interfere with the production of the protein spikes associated with the infectivity of the virus and thereby reduce subsequent viral spreading.
- The scientist’s viral strategy is based on research Gallicano and his collaborators have been conducting to treat heart failure, which uses miRNA to target genes that can affect the heart’s ability to function well. Modifying this cardiac approach, the researchers showed that miRNAs and siRNAs can target messenger RNA inside a virus. As SARS-CoV-2 uses messenger RNA to generate the proteins necessary for multiplication and infection, the ability to target viral machinery within cells via siRNA, in particular, could help shut the virus down, noted Gallicano.
- The scientists tested their approach using two types of cells in the lab, including one type of cell from a human windpipe (trachea). Against tracheal and non-tracheal cells, the researchers used siRNAs and found that they could suppress protein function in a dose-dependent manner, which they subsequently found was due to messenger RNA degradation.
- The researchers investigated if miRNAs and siRNAs would shut down production of proteins vital to a healthy cell. Through a series of experiments, they found that there were fewer ‘off-target’ effects using siRNA compared to miRNA; off-target effects can cause normal cells to go haywire.
- “If our approach proves successful in future experiments, we are confident this technology can be quickly moved from bench to bedside,” concludes Gallicano.
5. Seasonal rhythms within immune systems may explain infection rates
- Clocks and calendars within our immune systems could render us more susceptible to infection and injury at certain times of day or months of the year, a new study suggests. A better understanding of these rhythms could have implications for the prevention and treatment of diseases like C19. It could also help explain why certain illnesses, like flu, tend to strike in winter, while the symptoms of other diseases, like multiple sclerosis, often worsen in summer.
- Although recent studies have hinted that there may be seasonal or daily “circadian” rhythms in our immune function, this hadn’t been confirmed in large numbers of people until now.
- “It has been clear for centuries that people are more susceptible to certain diseases in winter, but we still don’t really understand the role our bodies play in that,” said Dr Cathy Wyse, a postdoctoral researcher at the Royal College of Surgeons in Ireland, who led the new research.
- To investigate, Wyse and colleagues turned to blood collected from some 329,261 participants in the UK Biobank study – which has followed the health of about half a million Britons for more than a decade – to see if the time of day or season when these samples were collected had any bearing on the immune cells they contained.
- They found clear fluctuations in the numbers of white blood cells and markers of inflammation in the blood, suggesting that our immune function may be stronger or weaker, depending on what time of day or season it is. “It supports the idea that there might be endogenous clocks and calendars in the immune system,” said Wyse, whose research was published as a preprint and has not yet been peer reviewed.
- Importantly, these variations were not related to environmental or lifestyle factors, or vitamin D levels: “This suggests such changes in our immune systems are due to our body clocks – the innate mechanisms that enable us to keep track of time,” said Dr Rachel Edgar at Imperial College London, who studies how viruses may exploit circadian rhythms to aid their spread.
- Indeed, the daily fluctuations observed in this study mirror patterns Edgar previously documented in mice, with white blood cells congregating in the lymph nodes at the start of the mice’s active period and moving into the blood as the mice progressed towards their rest phase. What happens in those lymph nodes is key to our immune response to vaccines and viruses like the coronavirus (Sars CoV-2): “In mice, the time of day that they are challenged [with a virus] has profound consequences for the immune response days later,” said Edgar. “This, coupled with evidence that the seasonal flu vaccine appears to be more efficacious when administered in the morning versus the afternoon, strongly suggests that certain Sars-CoV-2 vaccines may work better if administered early in the day.”
- This theory has not been tested, and Wyse cautions against over-interpreting her results. However, from an evolutionary perspective, it makes sense to coordinate the activities of your immune cells with when you are most likely to be active “The simplest interpretation is that the immune system has evolved to be better at recognizing and fighting potential pathogens during the daytime, because this is when humans would be most likely to come into contact with pathogens,” said Dr John O’Neill at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, who previously showed that cells involved in repairing tissue damage, migrate into wounds more quickly during the daytime.
- “These findings are an exciting confirmation of how biological timing is fundamentally important for human health, said Prof Tami Martino, distinguished chair in molecular cardiovascular research at the University of Guelph in Ontario, Canada. “From a lifestyle perspective, we can use this new understanding of biological timing to guide our behaviours, perhaps restricting our activity during the night or in winter seasons, so as to minimise our exposure to pathogens at the times when we are least resilient.”
- In separate research published last week, Martino discovered that the composition of the gut microbiome in mice also follows a day-night rhythm, and that feeding the mice during their rest period – which disrupted these microbial rhythms – impaired the mice’s ability to heal from heart damage.
D. Vaccines & Testing
1. Is Moderna’s Vaccine a Game-Changer?
- Moderna said its C19 vaccine was 94.5% effective in a preliminary analysis of a large late-stage clinical trial, another sign that a fast-paced hunt by scientists and pharmaceutical companies is paying off with potent new tools that could help control a worsening pandemic.
- The highly positive readout comes just a week after a similar shot developed by Pfizer and BioNTech was found to be more than 90% effective in an interim analysis. Both shots rely on a technology called messenger RNA that has never been used to build an approved vaccine. Soon, millions of people around the world could soon be spared from illness by the breakthroughs.
- A preliminary analysis of data from more than 30,000 volunteers showed Moderna’s vaccine prevented virtually all symptomatic cases of C19, the disease caused by the coronavirus, the company said in a statement on Monday.
- Only 5 participants who received two doses of the vaccine became sick, compared with 90 coronavirus cases in participants who received a placebo, according to a review of the data by an independent data safety monitoring board appointed by the US National Institute of Health.
- The vaccine also appeared to be effective in preventing the most serious C19 infections. There were no severe cases among people who got the vaccine, compared with 11 such cases in volunteers who received placebo shots, according to Moderna’s statement.
- “The thing that got me the most excited today was the [lack of] severe disease among those taking the vaccine,” Moderna Chief Executive Officer Stephane Bancel said in an interview. “That for me is a game-changer.”
Source: Bloomberg Coronavirus Daily
Also see: Moderna’s coronavirus vaccine found to be nearly 95% effective in a preliminary analysis @ https://www.washingtonpost.com/health/2020/11/16/covid-moderna-vaccine/
Moderna’s C19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study @ https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy
2. With strong data on 2 C19 vaccines, we have more answers about the road ahead — and questions too
- The success of a second vaccine against C19 means the world is a big step closer to curbing the coronavirus pandemic.
- Moderna, joined by U.S. government scientists, announced Monday that their mRNA vaccine candidate was 94.5% effective in preventing C19, according to an interim analysis of a 30,000-patient clinical trial. The news comes exactly one week after Pfizer and BioNTech said their respective C19 vaccine candidate, also created using mRNA technology, was more than 90% effective in its own 60,000-patient clinical trial.
- Here’s what we know — and still need to learn — about the two most advanced C19 vaccines and how they might reshape the pandemic that has killed 1.3 million people worldwide and infected at least 54.5 million.
Are the two vaccines equally effective?
- It’s too early to tell for certain, but the overall efficacy of the vaccines appears to be similar, based on the data disclosed to date. This isn’t altogether surprising, since the Moderna and the Pfizer/BioNTech vaccine candidates are both based on the same kind of technology.
- Based on data disclosed Monday, the Moderna vaccine appears to have been protective in important subsets of participants — the elderly and people from communities of color, the latter of which make up 37% of the volunteers in Moderna’s trial.
- Moderna also released data about the number of participants who developed severe C19. There were 11 cases of severe disease, all of them in the placebo group. The elderly often respond less robustly to vaccines and are more vulnerable to having severe cases of C19, if infected.
- The clinical trial conducted by Pfizer and BioNTech included the same subpopulations of participants, but specific results have not been disclosed.
We don’t know how effective these vaccines are in the long-term
- Some immunizations provide protection against a pathogen for decades (think the measles vaccine). It’s thought that the benefits of a C19 vaccine — no matter the manufacturer — won’t last nearly as long. But researchers won’t know how long until the immunity offered by these vaccines begins to wear off. This will be something scientists keep an eye on in the months to come.
- “We do not know at this point what the durability of protection will be,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said on a call with reporters Monday.
- How long vaccine-derived protection lasts has implications not only for manufacturing and how frequently people might be required to get boosters, but also for the ongoing risk of transmission of the coronavirus (SARS-CoV-2).
- There are other unanswered questions about these vaccines as well. For one, the trials were designed primarily to look at the impact on symptomatic C19. But experts will also want to see if the vaccine candidates can block infections entirely, or if they’re just making people less sick. Another: If people can still contract SARS-2 after getting vaccinated, are they less infectious to other people?
The safety profile of the vaccines is encouraging, so far
- So far, both vaccines appear to be generally tolerable — but by no means painless. In its announcement Monday, Moderna said it observed a few short-lived severe side effects in volunteers, including fatigue, muscle pain, and headache. None required hospitalization. For its part, Pfizer said last week that its independent data monitors reported no serious safety concerns. In an earlier update from its Phase 1 clinical trial, Pfizer’s vaccine led to mild or moderate fever and pain at the site of injection, side effects that resolved over time, the company said.
- But the most important safety data won’t come until patients have been followed for months and even years. Pfizer and Moderna have promised to collect and disclose that information in time.
What does this mean for the other vaccines in development?
- While both the Moderna and the Pfizer/BioNTech vaccines are based on mRNA technology, the other frontrunners — from AstraZeneca and Johnson & Johnson — use different approaches. (Other companies, including Sanofi, are at work on mRNA vaccines, but their candidates are not as far along in the development process.)
- But all the top candidates are targeting the virus’ spike protein, which the pathogen uses to infect cells. The results from the Pfizer and Moderna trials give hope that other vaccine candidates could be effective as well, given that they’re all going after the same bull’s-eye.
- “Today’s announcement provides further confirmation that spike-directed vaccines can provide a protective immune response,” said Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations, known as CEPI.
What does this mean for mRNA?
- Outside of its implications for the global pandemic, the tandem success of Moderna and Pfizer’s vaccines is a massive affirmation of the promise of mRNA, a medical technology that has advanced in fits and starts for three decades.
- At the start of 2020, SARS-2 was a virus that had never been studied, or even known. Less than a year later, two companies have developed what appears to be an effective vaccine for it. That suggests mRNA technology can be used to rapidly design and deploy vaccines for other pathogens. In Moderna’s case, it bodes well for in-development vaccines for Zika virus and cytomegalovirus, and it supports the company’s long-term plan to get into the business of manufacturing flu vaccines each year. For Pfizer’s partner BioNTech, which is developing vaccines for cancer, HIV, and influenza, it’s similarly encouraging.
- At the same time, vaccines have always been the lowest hanging fruit in the minds of mRNA researchers. The baseline promise of mRNA is that it can compel cells in the body to manufacture a specific protein, treating or preventing disease in the process. But developing mRNA medicines has always been a delicate balance: Scientists have to administer enough of the synthetic substance to ensure protein production, but not too much so as to avoid a dangerous immune reaction.
- Vaccines, which require only one or two doses of mRNA, are the most logical application of the technology. The bigger — and more lucrative — use for mRNA would be therapeutics for the scores of diseases that can be treated by making certain proteins in the body. That would require routine and lifelong administrations of mRNA, something neither Moderna nor BioNTech is yet to crack in a large clinical trial.
When can I get a vaccine?
- Both Moderna and Pfizer have promised to file for emergency use authorizations in the coming weeks. If the FDA grants them, as it’s widely expected to do before the end of the year, the companies will ship doses to the federal government, which is in charge of allocating the limited supply to front-line workers and people at an elevated risk of severe C19.
- For everyone else, neither vaccine is likely to be available until spring at the earliest, in large part because of logistics. (By that time, Pfizer and Moderna are also likely to have generated enough supporting data to justify full FDA approvals.) Pfizer and Moderna expect to produce just 70 million doses of their vaccines by the end of 2020, enough for only 35 million people around the globe. In 2021, the companies could have as many as 2.3 billion doses between them, but in a pandemic-ravaged world of 7.5 billion people, that’s not going to be enough to satisfy demand. Unless more C19 vaccines prove to work in the coming months, the world will be rationing doses well into next year.
- Further complicating matters is the issue of storage. Pfizer is capable of manufacturing more doses than Moderna, but its vaccine must be shipped and stored at ultra-cold temperatures, which could make it difficult to deploy in parts of the world that lack specialized freezers. By contrast, Moderna said its vaccine can be safely stored in a conventional refrigerator. That sets up a short-term situation in which Pfizer’s vaccine is the most bountiful but Moderna’s is the most convenient, which will require some deft maneuvering on the part of global health agencies.
Vaccines are important, but only if people get them
- Public health experts are quick to tell you: Even the world’s best vaccine won’t do much unless people are willing to get it.
- This has been a particular concern with C19 vaccines, as polls show that a substantial portion of Americans — whether because of how fast the process has moved or because of concerns that the vaccine review process would become politicized — said they would not get a C19 vaccine when it became available. Skepticism about C19 vaccines was even higher among people of color, who have experienced historic and ongoing mistreatment and discrimination in health care, and who are suffering from a disproportionate impact of the pandemic in the United States.
- As vaccines start to roll out, the supply will be so limited that they’ll be used for frontline workers or people more vulnerable to C19. But eventually, immunizations will be more widely available, and the majority of Americans will need to get vaccinated if the pandemic is going to draw to a close. Health authorities planning for the allocation and distribution of C19 vaccines have been taking this into account as they’ve charted out their campaigns.
- There’s another piece of good news in just how effective the Pfizer and Moderna vaccines appear to be. Experts believe — and polling data supports — that reluctance to get vaccinated may abate in some quarters if the vaccines work well. The public has been more or less warned these vaccines might be flu vax redux — and at least half the public doesn’t think flu vax is worth getting. A highly efficacious vaccine bodes well for uptake.
3. Testing Bottlenecks Again Gripping U.S. With Coronavirus Surging
- A surge in coronavirus cases, paired with rising demand for testing before the holidays and continued supply shortages, are putting renewed pressure on U.S. testing systems.
- The American Clinical Laboratory Association, whose members do about half of the country’s testing, said late last week it is seeing a big increase in test orders with the demand expected to continue ahead of Thanksgiving. As a result, turnaround times of around two days could increase as labs reach or exceed their testing capacities in the coming days, the group warned.
- Meanwhile, labs are also grappling with supply shortages, including pipette tips — used to transport samples during the testing process — and swabs. Though the government has invested in manufacturers to build out capacity, that will take into 2021 to pan out, said Scott Becker, head of the Association of Public Health Laboratories.
- “All of the issues we uncovered in the spring and lived through in the summer haven’t gone away completely,” Becker said by telephone. “With this massive surge in cases, it’s natural to see that testing will unfortunately slow down.”
- America’s testing apparatus has remained in a state of continued strain. Test-positivity rates have exceeded a World Health Organization-recommended threshold of 5% in the vast majority of U.S. states, according to Johns Hopkins data.
- Some of the highest numbers were in Iowa, South Dakota and Kansas, where more than half of tests done in the last week returned positive results. That suggests testing is only capturing a fraction of total cases.
- At the same time, rising cases have limited the ability to use a technology known as pooling to process multiple samples at a time, as pooling is most efficient in areas of low virus prevalence, according to Becker. And although new rapid screening technologies have become more widely available, they haven’t relieved the burden on more conventional testing infrastructure.
- As cases rose in recent weeks, the federal government set up “surge” virus testing sites offering gold-standard polymerase chain reaction tests within 10 states. It’s also been deploying surge shipments of Abbott Laboratories’ BinaxNOW, a cheap, rapid test that doesn’t need to be sent to a lab, to Wisconsin and now Utah and Pennsylvania, Brett Giroir, an HHS official who leads the administration’s C19 diagnostic testing efforts, said at a Monday briefing.
- At the briefing, Giroir also said the U.S. Department of Health and Human Services was taking measures to ensure laboratory-developed tests undergo a voluntary review by the Food and Drug Administration within 14 days, so universities and other developers like health systems can get C19 testing up and running.
- Giroir, meanwhile, maintained that turnaround times have remained reasonable in most of the country.
- Asked specifically about long lines reported in states, “I’m sure what’s causing it is we have 180,000 new cases and the pandemic is really at a critical point,” Giroir said.
- “This is not like a few Ebola cases that you can test and trace. We cannot test our way out of this,” he said. “We have to do the large-scale mitigation efforts,” such as masking and social distancing.
- In New York City, where rising test positivity has resulted in new restrictions and threatened to close schools, urgent care provider CityMD said late last week that demands for C19 tests and other care had made long lines “a daily fact” at most of its locations, keeping providers late. Starting on Monday, the facilities will close about an hour and a half earlier, helping curtail lines, the company said.
- Test-seekers in New York City also encountered lines early this week with hours-long waits. Noting that the state has long had some of the most robust testing capacity in the country, New York Governor Andrew Cuomo said on Friday that the issue likely reflects that “the problem exists in every state and is worse in every other state.”
4. Rapid C19 Antibody Test Is Not as Accurate as We Were Told
- A rapid finger-prick test designed to show whether a person has previously been infected with the coronavirus (SARS-CoV-2) is significantly less accurate than earlier research suggested, scientists report in a new study.
- The AbC-19 Rapid Test, developed for use by healthcare professionals in the UK and EU, looks for antibodies against the virus in a small drop of blood from a finger-prick, and can show results in just 20 minutes, without needing specialised lab equipment.
- The idea is that healthcare workers can quickly and easily run the test in public at points of care, and receive results on the spot to provide insight into how many people in the community have antibodies against SARS-CoV-2 – a strong selling point that led the UK government to order a million of the test devices for £75 million (almost US $100 million).
- That order was also guided by positive results of an “extensive validation study” funded by the UK-Rapid Test Consortium – a body that represents commercial companies, including Abingdon Health and Omega Diagnostics, which developed AbC-19.
- That study, led by researchers from Ulster University in Northern Ireland, is publicly available but is still awaiting peer review.
- It found, effectively, that the AbC-19 Rapid Test would give no false positive results, with a specificity of 100 percent. Specificity is the ability to correctly identify a true negative sample, rather than give a false negative.
- The Ulster study also found that the test’s sensitivity was 97.7 percent. Sensitivity is the ability to correctly identify a true positive sample.
- Now, however, a new independent study of AbC-19 has found significantly different results in terms of the finger-prick test’s accuracy.
- A team of scientists from the Universities of Bristol, Cambridge, and Warwick analysed blood samples from 2,847 key workers (healthcare workers and first responders) – 268 of which had previously delivered a positive PCR result for COVID, while 2,579 had an unknown previous infection status.
- In addition, they tested samples from 1,995 pre-pandemic blood donors (known negatives from before the coronavirus pandemic).
- The results of the new study suggest AbC-19’s specificity is 97.9 percent (not 100 percent, as the Ulster study claimed), and its sensitivity is 92.5 percent (based on PCR confirmed cases) but can drop as low as 84.7 percent in cases where prior infection status is entirely unknown.
- The differences between the two studies likely reflect differences in how the two groups tested the AbC-19 device, but it’s being suggested that the Ulster research didn’t provide as clear a picture as it might have of the test’s accuracy.
- “[The Ulster study] chose as known positives people who had already tested positive for antibodies to SARS-CoV-2 proteins in three other assays and chose as known negatives people who tested negative in the same three assays,” two clinical experts, Dipender Gill and Mark J Ponsford, write in a commentary article on the new study’s findings.
- “Such a relatively extreme choice of reference standards likely overestimated the accuracy of the AbC assay, owing to a well known phenomenon called spectrum bias.”
- Extrapolating further, the independent study – led by first author Ranya Mulchandani from the UK Field Epidemiology Training Program – found one in five key workers testing positive with AbC-19 would be a false positive, in a scenario where 10 percent of the tested population had been infected with SARS-CoV-2.
- While no test is ever perfect, the reported reduced accuracy of the AbC-19 test is something people should be aware of, researchers say.
- “These new data are very useful at a public health level,” says infectious diseases researcher Eleanor Riley from the University of Edinburgh, who wasn’t involved with the studies.
- “If we know how many cases the test is missing, and how many it is wrongly calling positive, we can adjust our population estimates of prior infection accordingly.”
- For its part, the UK Department for Health & Social Care (DHSC) insists the new findings aren’t a problem for AbC-19’s intended use – which is in monitoring prior infections in the community, from a healthcare level, and not diagnosing current C19 infections in members of the public.
- “This report shows these tests are approved for use in surveillance studies, which is what they were purchased for,” a statement reads.
- “They were never intended for, and have never been issued for widespread public use and it is misleading and unnecessarily inflammatory to purposefully ignore this fact in the report.”
- Nonetheless, the fallout from these new revelations may be considerable. There are allegations that the UK government delayed the findings of the new study, and already legal proceedings have commenced against the government in relation to the tests.
E. Improved & Potential Treatments
1. Arthritis drug cuts C19 deaths in hospitalized patients by two-thirds
- An arthritis drug may cut deaths in hospitalized C19 patients by about two thirds among those suffering from moderate or severe cases of the virus, according to a new study.
- Called baricitinib, and marketed under the brand name Olumiant, the medication has been touted by its British company as a possible game changer in the fight against C19, the Daily Mail reported.
- The rheumatoid arthritis drug, which has been available for only three years, was identified in February as a strong candidate to help treat what was then the emerging threat of the novel coronavirus, according to the outlet.
- London-based BenevolentAI examined thousands of existing drugs for signs they might be effective against the deadly bug. The company’s artificial intelligence program predicted that the arthritis drug would “reduce the ability of the virus to infect lung cells,” the Daily Mail reported.
- And now, a study by European researchers and led by Sweden’s Karolinska Institute found that baricitinib dramatically cut death rates in C19 sufferers admitted to a hospital by about 70 percent.
- The results, published in the journal Science Advances, came from 83 patients who were treated with the drug while hospitalized with coronavirus pneumonia at two hospitals in Italy and Spain.
- “We are pleased to report a 71 percent reduction in mortality for the group receiving baricitinib in addition to standard care,” said Karolinska Institute Professor Volker Lauschke, who led the study.
- “These results are especially encouraging seeing as the study included a large cohort of elderly patients, a group often excluded.”
- Professor Justin Stebbing, a cancer specialist at Imperial College London, predicted that the medication could help save thousands of lives.
- “The history of treatments for COVID has not left many drugs standing. What has been left standing is two British-discovered drugs,” he said, the Daily Mail reported.
- The other is the steroid dexamethasone, which has been found to cut the risk of death among severely ill coronavirus patients by 33 percent.
Also see: Two anti-inflammatory compounds shown to be capable of accelerating recovery from C19 at https://www.eurekalert.org/pub_releases/2020-11/icl-csa111320.php
2. Doctors Consider Convalescent T Cell Therapy for C19
- Physicians and researchers have had questionable success treating patients with severe C19 with either antibody-based drugs or convalescent plasma. Neither of those strategies is a cell-based therapy, and, in a preprint posted October 26 on bioRxiv, researchers propose collecting coronavirus (SARS-CoV-2)–specific memory T cells from recovered individuals, banking the cells, and infusing them into patients as a treatment for infections.
- “There are data now that are coming out from the analysis of the immune response that are suggesting that the T cells are more important for protection than antibodies,” says Antonio Bertoletti, who studies the development of immunological therapies at Duke-NUS Medical School in Singapore and did not participate in the work. There is therefore a rationale to use T cells to control the disease, he adds.
- Previously, researchers had attempted memory T cell therapy to suppress cytomegalovirus and Epstein Barr virus. The recipients were leukemia patients who received a stem cell transplant to treat their cancer at the same time. It was this success, combined with the T cell findings from C19 patients, that led Antonio Pérez-Martínez, a pediatrician at Hospital Infantil Universitario La Paz in Madrid, and his colleagues to consider a cell-based treatment for the coronavirus.
- The researchers isolated memory T cells, including some that released interferon gamma, a cytokine necessary for anti-viral immunity, upon exposure to SARS-CoV-2 antigens, from the blood of people who recovered from C19. They showed that it was possible to freeze, store, and thaw these cells and propose that biobanks of memory T cells could be created from convalescent donors to be infused to treat disease. The practice of storing convalescent plasma, which includes antibodies but no immune cells, to treat C19 patients is already in wide use, although with mixed data on its utility.
- “If you give plasma and antibodies, those antibodies could potentially fight COVID, but they are not produced in that person, so they are just have a normal half-life and they are cleared,” says Rory de Vries, an immunologist at Erasmus University Medical Center in the Netherlands who did not participate in the study. But when T cells encounter a virus, “they start expanding, and you might actually build your own new immunological memory while you’re doing that, which will never happen with plasma.”
- Despite the theoretical potential, “it’s not an easy approach,” de Vries cautions. For one thing, the authors “don’t only store SARS-CoV-2 specific T cells, they store every memory cell, so that means that you also store your memory for measles or . . . previous vaccinations,” he tells The Scientist. “And if you infuse these T cells, I don’t think we really know what might happen.”
- In a cell-based treatment, there are also concerns about immunological compatibility of the donor and recipient, just as there would be during an organ transplant, de Vries explains. The authors did characterize memory T cells based on human leukocyte antigens (HLA), molecules responsible for the immune system’s ability to distinguish self and non-self. But de Vries cautions that HLA diversity is vast, potentially requiring more extensive characterization than the authors have done in the preprint to make the treatment safe.
- According to Pérez-Martínez, the HLA matching is sufficient because patients with severe C19 have lymphopenia, a dearth of white blood cells called lymphocytes, a subtype of which are T cells. Lymphopenia is a biological marker of severe C19, he says. The patients who are more lymphopenic have a greater chance of ending up in the ICU and eventually dying.
- The lymphopenia triggered by the coronavirus is similar to the lymphopenia induced by chemotherapy drugs in patients before a stem cell transplant, so the transplant won’t be rejected, he explains. This “lymphopenic window” during C19 is the time at which it could be possible to replace a patient’s missing lymphocytes with SARS-CoV-2-responsive T cells from recovered donors. The idea is that lymphopenic patients don’t have enough of their own T cells, so they’re not going to reject donor lymphocytes.
- This strategy “is complicated and needs some work,” says Bertoletti. “It could be that for a short time . . . when you are introducing these T cells in a patient, they will be basically able to suppress viral replication and kill the infected cells,” he adds, but the unanswered questions of how important HLA matching is and what the appropriate timing for such a treatment complicates matters.
- In order to test the safety of the treatment, Pérez-Martínez and colleagues are beginning a Phase I clinical trial in patients hospitalized for C19 with lymphopenia. In the transplant setting, doctors have not seen any side effects, he says, “so I think that it’s worth it to try.”
3. Two anti-inflammatory compounds shown to be capable of accelerating recovery from C19
- Two independent clinical studies – one by researchers at the Center for Cell-Based Therapy (CTC) in Ribeirão Preto, state of São Paulo (Brazil), on the monoclonal antibody eculizumab, and the other by scientists at the University of Pennsylvania in Philadelphia (USA) on an experimental drug called AMY-101 – observed a significant anti-inflammatory effect that contributed to a faster recovery by severe C19 patients. The results of the two studies, which set out to compare the compounds’ therapeutic potential, are reported in an article published in Clinical Immunology.
- The two medications were administered separately. The monoclonal antibody, routinely used to treat blood diseases, was tested on patients at the teaching hospital (“Hospital das Clínicas”) run by the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP). AMY-101, a candidate drug developed by US-based pharmaceutical company Amynda, was given to patients at a hospital in Milan, Italy. Both produced promising results, but because AMY-101 is cheaper and performed better in the clinical trial, the two research groups envisage testing it on a larger number of patients in Brazil.
- “Both compounds caused a robust anti-inflammatory response that culminated in a fairly rapid recovery of respiratory function in the patients,” Rodrigo Calado, who led the study at FMRP-USP, told Agência FAPESP. Calado is affiliated with CTC, a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP and based at FMRP-USP’s blood center.
- The researchers concluded that the therapeutic benefits of eculizumab and AMY-101 were due to inhibition of a bloodstream cascade of proteins involved in immune response and known as the complement system.
- Persistent dysregulated complement activation triggers the exacerbated inflammatory response to the coronavirus (SARS-CoV-2) infection characterized by a systemic increase in pro-inflammatory cytokines and often referred to as a “cytokine storm”.
- Unable to prevent infection of cells by the virus, the complement system enters a spiral of runaway continuous activation that leads to massive infiltration of monocytes and neutrophils into the infected tissues. This process can result in inflammatory damage to the walls of blood vessels surrounding vital organs, as well as disseminated microvascular injury and thrombosis, potentially culminating in multiple organ failure.
- “Previous studies had shown the use of complement inhibitors to be a promising therapeutic strategy to ameliorate thromboinflammation in C19 patients, and there were reports of cases with positive results,” Calado said. “However, as yet no one had elucidated the action or evaluated the efficacy of drugs already in use to treat diseases caused by complement alterations, such as eculizumab, or candidate drugs with this function such as AMY-101.”
- To fill the gap the researchers conducted two clinical studies in which they compared the biological efficacy of eculizumab with that of the synthetic peptide AMY-101 in independent small groups of severe C19 patients.
- Ten patients aged between 18 and 80 were undergoing treatment at FMRP-USP’s Hospital das Clínicas. Once a week while hospitalized, they were given 900 mg of eculizumab, which inhibits the complement protein C5. Three patients hospitalized in Milan, Italy, were given 5 mg of AMY-101, developed to inhibit complement protein C3, also once a week. These two proteins perform the most important activities in the complement system.
- The patients’ clinical responses showed that eculizumab and AMY-101 elicited a robust anti-inflammatory process, a sharp fall in levels of C reactive protein (CRP) and interleukin-6 (IL-6), and a marked improvement in lung function.
- Inhibition of C3 by AMY-101 afforded broader therapeutic control, stronger lymphocyte recovery, a pronounced decline in neutrophil count, and more robust attenuation of the thromboinflammation induced by the exacerbated response to viral infection.
- “The results of the clinical trials showed that inhibiting components of the complement system sharply reduces inflammation,” Calado said.
New clinical study
- In light of the promising results of the two clinical trials, the CTC and UPenn researchers now plan to conduct a Phase 3 trial with more than 100 severe C19 patients, who will be given only AMY-101 in an effort to assess the drug’s efficacy on a wider scale.
- The study will be conducted at FMRP-USP’s Hospital das Clínicas, and will probably involve other research institutions in Brazil. “One of the advantages of AMY-101 is its low cost. It’s much less expensive than eculizumab,” Calado said.
4. Promising New Drug Compounds Identified to Potentially Treat Viruses Like C19, Flu & Ebola
- Researchers at the University of Maryland School of Medicine (UMSOM) and School of Pharmacy (UMSOP) have discovered new drug compounds to potentially treat the novel coronavirus that causes C19. The compounds disrupt the functioning of a protein complex inside human cells that the researchers discovered is critical for the replication and survival of coronaviruses. This finding could lead to the development of new broad-spectrum antiviral drugs that target viruses such as influenza, Ebola, and coronaviruses, according to a new study published today in the Proceedings of the National Academy of Sciences (PNAS) journal.
- The protein complex, called SKI complex, is a group of human proteins that regulates various aspects of the normal functioning of a cell. In the new study, the researchers discovered that this complex also plays a crucial role in helping a virus replicate its genetic material, called RNA, within the cells it infects.
- “We determined that disrupting the SKI complex keeps the virus from copying itself, which essentially destroys it,” said study corresponding author Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at the UMSOM. “We also identified compounds that targeted the SKI complex, not only inhibiting coronaviruses but also influenza viruses and filoviruses, such as the one that causes Ebola.”
- He and his colleagues from the School of Pharmacy’s Computer-Aided Drug Design Center and the Center for Biomolecular Therapeutics at the UMSOM used computer modeling to identify a binding site on the SKI complex and identified chemical compounds that could bind to this site. Subsequent experimental analysis showed these compounds to have antiviral activity against coronaviruses, influenza viruses, and filoviruses (such as Ebola). Researchers from the National Institute of Allergy and Infectious Diseases also participated in this study.
- The study was funded by Emergent BioSolutions, a biopharmaceutical company based in Gaithersburg, MD.
- “These findings present an important first step in identifying potential new antivirals that could be used to treat a broad number of deadly infectious diseases,” said study lead author Stuart Weston, PhD, a research fellow at the UMSOM. Such drugs have the potential to treat infectious disease associated with future pandemics. Next steps include conducting animal studies to learn more about the safety and efficacy of these experimental compounds, which are not approved by the FDA.
F. Concerns & Unknowns
1. Exposure to C19 Could Pose a Risk to the Health and Aging of Individuals Who Aren’t Even Born Yet
- Exposure to C19 could pose a risk to the health and aging of individuals who aren’t even born yet, according to a newly published analysis by USC researchers.
- In the article, University Professors Eileen Crimmins and Caleb Finch of the USC Leonard Davis School of Gerontology and Keck School of Medicine neonatology fellow Molly Easterlin note that by the end of 2020, approximately 300,000 infants could be born to mothers infected by the coronavirus (SARS-CoV-2). Millions more will be born into families who have experienced tremendous stress and upheaval due to the pandemic even if they haven’t been infected themselves, the authors added.
- While the longer-term effects of C19 on infants is yet to be seen, researchers can find some insight from the past, including the 1918 flu pandemic and previous coronavirus illnesses such as SARS in 2002 and MERS in 2012, Finch said.
- “The 1918 influenza pandemic had long-term impacts on the cohort exposed in utero, which experienced earlier adult mortality and more diabetes, ischemic heart disease and depression after age 50,” he said. “It is possible that the C19 pandemic will also have long-term impacts on the cohort that was in utero during the pandemic, from exposure to maternal infection and/or the stress of the pandemic environment.”
- Maternal viral infections can affect fetuses through multiple pathways, from direct transmission through the placenta to inflammatory responses that disturb in-utero metabolism and negatively affect growth. While direct maternal-fetal transmission of the virus and severe birth defects appear to have been rare during previous coronavirus outbreaks, there were increases in preterm delivery and low birth weight during both the 2002 SARS and 2009 H1N1 influenza outbreaks, which are possible consequences of increased inflammation.
- While studies on C19 and pregnancy are still in their early stages, there have already been some concerning results that merit a closer look in ongoing studies, the authors wrote. Increased rates of preterm birth may be linked to maternal SARS-CoV-2 infections, and other studies indicate that severe illness is correlated with a higher risk of stillbirth. Other potential dangers, including the increased risk of blood clots presented by both pregnancy and severe C19, also need further study.
- “We suggest that to capture the consequences of viral exposure in utero for childhood development and adult health, C19 birth cohort studies consider immediate collection of data from the mother, fetus, neonate, and placenta,” Easterlin said. “These initial data should be followed by analysis of child growth and development and lifelong study of health, behavioral patterns, and cognitive functioning.”
- In addition to the direct risks posed by infection, the C19 pandemic has also increased levels of stress, unemployment, food insecurity, and domestic violence, and diminished or disrupted prenatal care. For these reasons, the researchers suggest that cohort studies also include non-infected mothers and children as well as compare the C19 cohort to children born before or after the pandemic and include various socioeconomic measures.
- “The inclusion of information on social and economic stresses will allow comparisons between countries taking different measures to reduce spread of the virus,” Crimmins said. “These types of comparisons may give us further insights beyond the effects of COVID, such as socioeconomic and social policies that may decrease risk of preterm birth.”
2. Life After COVID Hospitalization: Major Lasting Effects on Health, Work & More
- Surviving a case of C19 that’s bad enough to land you in the hospital is hard enough. But life after the hospital stay — and especially after an intensive care stay — is no bed of roses, either, according to a new study.
- Within two months of leaving the hospital, nearly 7% of the patients had died, including more than 10% of the patients treated in an ICU, and 15% ended up back in the hospital. The data come from more than 1,250 patients treated in 38 hospitals across Michigan this spring and summer, when the state was one of the earliest to experience a peak in cases.
- When researchers interviewed 488 of the surviving patients by phone around 60 days after their hospitalization, they heard a litany of health and life woes. They’ve published their findings in the Annals of Internal Medicine.
- “These data suggest that the burden of C19 extends far beyond the hospital and far beyond health,” says Vineet Chopra, M.D., M.Sc., lead author of the study and chief of hospital medicine at Michigan Medicine, the University of Michigan’s academic medical center. “The mental, financial and physical tolls of this disease among survivors appear substantial.”
- More than 39% of the patients interviewed said they hadn’t gotten back to normal activities yet, two months after leaving the hospital. 12% of the patients said they couldn’t carry out basic care for themselves anymore, or as well as before.
- Nearly 23% said they became short of breath just climbing a flight of stairs. One-third had ongoing COVID-like symptoms, including many who still had problems with taste or smell.
- Of those who had jobs before their bout with C19, 40% said they couldn’t return to work, most because of their health and some because they’d lost their job. And 26% of those who had gone back to work said they had to work fewer hours or have reduced duties because of their health.
- Nearly 50% of those interviewed said they’d been emotionally affected by their experience with C19 — including a minority who said they’d sought mental health care.
- More than a third — 37% — of those interviewed said their experience with C19 had left them with at least a minor financial impact. Nearly 10% said they’d used up most or all of their savings, and 7% said they were rationing food, heat, housing or medications because of cost.
- “The sheer number of people struggling after COVID brings new urgency to developing programs to better promote and support recovery after acute illness,” says Hallie Prescott, M.D., M.Sc., senior author and pulmonary/critical care physician at University of Michigan and the VA Ann Arbor Healthcare System.
More about the study
- The study used date from the MI-COVID19 initiative, which rapidly evolved in April as a way for Michigan hospitals to pool and analyze data on their C19 patients.
- It grew out of existing multi-hospital quality improvement efforts funded by Blue Cross Blue Shield of Michigan, and drew on existing staff who are experienced at analyzing medical records and interviewing patients. That gave researchers a head start on studying C19 patients treated in most of the hospitals that received such patients in the early-peak state of Michigan.
- Details obtained from patient medical records, and in-depth interviews conducted after attempting to contact patients by phone multiple times, give a picture of what life is like for post-COVID patients.
- Nearly 52% of the patients in the study are Black, and 4% are Hispanic. The average age is 62, and 83% lived at home before being hospitalized for C19.
- More than 14% had no chronic conditions before C19 landed them in the hospital, and for many others the only condition they had was high blood pressure. The well-known risk factors of diabetes, cardiovascular disease and kidney disease were present in about 25% of patients.
- While hospital care for C19 patients has improved since the early months of the pandemic, the study shows that the 63% of patients who were ever treated in an ICU had died during their hospital stay or within two months of leaving the hospital. That’s more than twice the rate for patients hospitalized but not admitted to an ICU.
3. Why does C19 seem to spare children?
- Researchers at Vanderbilt University Medical Center (VUMC) and their colleagues have determined a key factor as to why C19 appears to infect and sicken adults and older people preferentially while seeming to spare younger children.
- Children have lower levels of an enzyme/co-receptor than the coronavirus (SARS-CoV-2) needs to invade airway epithelial cells in the lung.
- The findings, published today in the Journal of Clinical Investigation, support efforts to block the enzyme to potentially treat or prevent C19 in older people.
- “Our study provides a biologic rationale for why particularly infants and very young children seem to be less likely to either get infected or to have severe disease symptoms,” said Jennifer Sucre, MD, assistant professor of Pediatrics (Neonatology), who led the research with Jonathan Kropski, MD, assistant professor of Medicine.
- Sucre and Kropski are co-corresponding authors of the paper. Bryce Schuler, MD, PhD, a resident in Pediatrics and Genetics at VUMC and postdoctoral fellow in the Vanderbilt Stimulating Access to Research in Residency program, is the paper’s first author.
- There is still much to learn about SARS-CoV-2. But this much is known: After a viral particle is inhaled into the lungs, protein “spikes” that stick out like nail studs in a soccer ball attach to ACE2, a receptor on the surfaces of certain lung cells.
- A cellular enzyme called TMPRSS2 chops up the spike protein, enabling the virus to fuse into the cell membrane and “break into” the cell. Once inside, the virus hijacks the cell’s genetic machinery to make copies of its RNA.
- Sucre and Kropski, who have collaborated since 2016 on studies of lung diseases in premature infants and adults, wondered if TMPRSS2 had something to do with the greater severity of C19 symptoms observed in older people compared to children.
- “Our research has always focused on understanding lung development and how infant lungs differ from adult lungs in their vulnerability to injury,” Sucre said. “In this study we actually took the opposite approach, and were able to see how the developing lung by its differences is protected from SARS-CoV-2 infection.”
- The researchers were well equipped to begin such a study. As members of the international Human Cell Atlas (HCA) Lung Biological Network, they and their colleagues had built a dataset on lung development in the mouse using a technique called single-cell RNA-sequencing.
- The technique can detect the expression of genes in individual cells of tissues such as the lung. In this way the researchers were able to track the expression of genes known to be involved in the body’s response to C19 over time.
- They found that while the gene for ACE2 was expressed at low levels in the mouse lung, “TMPRSS2 stood out as having a really striking trajectory of increased expression during development,” Schuler said.
- With the help of VUMC pathologists, the researchers obtained and analyzed human lung specimens collected from donors of different ages, and confirmed a similar trajectory in TMPRSS2 expression to what they’d found in mice.
- “What we found is that expression of (TMPRSS2) goes up significantly with aging, and we see that at the level of the gene and at the level of the protein,” Sucre said. “We see a lot more TMPRSS2 in older individuals, in both humans and mice.”
- The researchers also used fluorescent probes to analyze autopsy specimens from three patients who died of C19, and found the virus in three types of cells that express TMPRSS2.
- TMPRSS2 is well known for its role in the development of prostate cancer. Drugs that block the enzyme and which have been approved for the treatment of advanced prostate cancer currently are being tested clinically as potential treatments for C19.
- The new findings reported today support further investigation.
- “We do think TMPRSS2 could be an attractive target both in treatment and potentially as a prophylaxis for (preventing infection in) people at high risk of COVID exposure,” Sucre said.
4. Measles Is Back With a Vengeance, Killed 200,000 in 2019; C19 Could Make it Worse
- A new report from the World Health Organization and the Centers for Disease Control and Prevention highlights a bleak reality: Measles, the highly contagious but vaccine-preventable viral illness, infected at least 860,000 people and killed over 200,000 worldwide in 2019—a roughly 50% jump in deaths from 2016. Sadly, the C19 pandemic is likely to make this situation even worse.
- Following the invention of a vaccine for measles in the 1960s, annual cases took a sharp plunge. In the U.S., the establishment of a nationwide vaccine program for childhood diseases led to the local elimination of measles in the year 2000. In 2016, cases globally reached a record low, leading to hopes it could be eradicated everywhere in the near future. But since those optimistic days, things have taken a sharp turn for the worse, especially in Europe.
- While there were only 5,000 or so documented cases across Europe in 2016, the next year saw over 21,000. By 2019, progress has slipped so far that the UK and several other countries lost their measles-free status from the WHO. That same year, relatively large outbreaks of measles in the U.S.—sparked by travelers returning from countries where the disease wasn’t contained—almost led to its status being stripped as well. Even still, the 1,200+ cases the U.S. documented in 2019 were more than it had seen since the early 1990s.
- Worldwide, according to the new CDC/WHO report released Thursday, there were 869,770 documented cases of measles in 2019, the highest annual number since 1996. Many cases of measles go unreported, so the true number is higher—somewhere around 9 million total, according to the report. It also estimated there were over 207,500 deaths in 2019. That’s half as many deaths as estimated in 2000, but a substantial jump from the 140,000 deaths estimated in 2018. Most measles deaths occur among children under the age of five.
- These increases could be seen across the world, but outbreaks were especially large and uncontrolled in Africa and Europe. The only two countries to achieve local elimination for the first time in 2019 were Iran and Sri Lanka. And though there are important regional differences for why cases have spiked, the underlying reason is the same.
- “In all WHO regions, the fundamental cause of the resurgence was a failure to vaccinate, both in recent and past years, causing immunity gaps in both younger and some older age groups,” the authors of the report wrote.
- Because measles is so highly contagious, it takes a very high vaccination rate to stop it from spreading within communities once it arrives—somewhere around 95%. The current vaccine used for measles, a combination shot that also protects against mumps and rubella, requires two doses, further complicating adherence. Adding to that is the anti-vaccination movement, which has contributed to a growing mistrust of vaccines in the U.S. and elsewhere.
- So far, cases of measles in 2020 worldwide aren’t looking to be as high as they were last year, possibly in part because of increased physical distancing due to the C19 pandemic. But there have already been documented declines in routine vaccinations this year in many countries, including the U.S. Experts at the WHO and elsewhere fear that the pandemic will set back efforts to contain a wide array of infectious diseases such as measles, HIV, and tuberculosis, particularly in already-struggling regions. Measles isn’t the only disease that threatens to overwhelm us, but it’s one of the most preventable.
- “Before there was a coronavirus crisis, the world was grappling with a measles crisis, and it has not gone away,” said Henrietta Fore, UNICEF executive director, in a statement released by the WHO. “While health systems are strained by the C19 pandemic, we must not allow our fight against one deadly disease to come at the expense of our fight against another.
5. C19 Testing Saps Supplies Needed for Other Medical Tests
- C19 tests have siphoned supplies crucial for other kinds of medical exams, including strep throat, fungal infections and sexually transmitted diseases, forcing some labs to ration testing for certain conditions.
- Doctors and laboratories face shortfalls of the swabs, chemicals and other equipment needed to test patients and process tests, partly because supply chains were rewired during the pandemic to ramp up production of C19 tests.
- Due to the shortages, some medical-testing labs have had to limit how many samples they can process and what conditions they can test for.
- Roughly 30% of labs surveyed the week of Oct. 26 by the American Society for Microbiology and the Association of Supply Chain Management said they were experiencing shortages of supplies to detect bacteria that cause infections such as strep throat, bronchitis and urinary-tract infections.
- Half of the 127 labs surveyed said they were short on supplies for routine fungal infections ranging from superficial skin conditions to serious lung and blood diseases, the society said.
- “We make the best of what we can, but the bottom line is, we still can’t get enough reagents. We still can’t get enough consumables,” said Patrick Godbey, a lab director in Georgia who is president of the College of American Pathologists.
- Shortages for some of the supplies eased the week of Oct. 26, as compared with the week before, according to the microbiology society’s data.
- Yet, Dr. Godbey and other laboratory directors say they expect the shortages to worsen in coming months, as flu testing gets under way and C19 cases continue to increase sharply, requiring more of the materials and equipment.
- The scarcities are a side effect of the buildup of C19 tests, more than one million of which are being performed each day. The scale-up sapped resources and spawned wider shortages in test-making plants.
- “A company can only make so much on its production line. People are screaming for Covid. Well, then something else has to give,” said Melissa Miller, director of microbiology laboratories at the University of North Carolina Medical Center and a committee chair for the American Society for Microbiology.
- Early in the pandemic, leading test-maker Hologic Inc. repurposed manufacturing designated for other infectious diseases, including chlamydia, gonorrhea and human papillomavirus, a company spokeswoman said.
- Demand for the other tests fell during shutdowns. In the past six months, Hologic roughly doubled its overall test-production capacity and supply of collection kit components, the spokeswoman said. The company is now increasing production for all of its molecular tests.
- As demand for non-coronavirus medical tests revives, labs have reckoned how to use the limited supplies and exams available.
- The University of North Carolina Medical Center has faced shortages of supplies needed to test for a type of bacteria, known by the shorthand MRSA, that is resistant to several antibiotics and causes staph infections, Dr. Miller said.
- When the supplies are scarce, she said, the lab must resort to an older testing method that might not yield results as accurate as the state-of-the-art technique.
- The most drastic shortages, lab officials say, has been for supplies needed to detect chlamydia and gonorrhea, which can harm reproductive health. Nearly 43% of labs surveyed during the week of Oct. 26 by the microbiology society faced shortages for those and tests for other sexually transmitted infections. The week before, the shortages affected just over 70% of surveyed labs.
- Some of the materials and equipment needed to test for sexually transmitted diseases overlap with those used in C19 diagnostics.
- Some efforts are under way to resolve the shortages. In its letter, the CDC said it was working with other health officials and agencies to understand the scope of the shortages and find possible solutions.
6. Obesity increases risk of getting C19 and dying
- The C19 pandemic has thrust the obesity epidemic once again into the spotlight, revealing that obesity is no longer a disease that harms just in the long run but one that can have acutely devastating effects. New studies and information confirm doctors’ suspicion that this virus takes advantage of a disease that our current U.S. health care system is unable to get under control.
- In most recent news, the CDC reports that 73% of nurses who have been hospitalized from C19 had obesity. In addition, a recent study found that obesity could interfere with the effectiveness of a C19 vaccine.
- I am an obesity specialist and clinical physician working on the front lines of obesity in primary care at the University of Virginia Health System. In the past, I often found myself warning my patients that obesity could take years off their life. Now, more than ever, this warning has become verifiable.
Why C19 Kills Some People and Spares Others
- The novel coronavirus causing C19 seems to hit some people harder than others, with some people experiencing just mild symptoms and others being hospitalized and requiring ventilation. Here’s why.
- Initially physicians believed that having obesity increased only your risk of getting sicker from C19, not your chance of being infected in the first place. Now, newer analysis shows that not only does obesity increase your risk of being sicker and dying from C19; obesity increases your risk of getting infected in the first place.
- In March 2020, observational studies noted hypertension, diabetes and coronary artery disease as the most common other conditions – or co-morbidities – in patients with more severe C19 disease. But it was the editors of Obesity journal who first raised the alarm on April 1, 2020 that obesity would likely prove to be an independent risk factor for more severe effects of C19 infection.
- Additionally, two studies including nearly 10,000 patients have shown that patients who have both C19 and obesity have a higher risk of death at days 21 and 45 compared to patients with a normal body mass index, or BMI.
- And a study published in September, 2020 reported higher rates of obesity in C19 patients who are critically ill and require intubation.
- It is becoming overwhelmingly evident from these studies and others that those with obesity are facing a clear and present danger.
Stigma and lack of understanding
- Obesity is an interesting disease. It is one that many physicians talk about, often in frustration that their patients cannot prevent or reverse it with the oversimplified treatment plan that we have been taught in our initial training; “Eat less and exercise more.”
- It is also a disease that causes problems physically, such as sleep apnea and joint pain. It also affects one’s mind and spirit due to societal and medical professionals’ bias against those with obesity. It can even adversely affect the size of your paycheck. Can you imagine the outcry if the headline read “Patients with high blood pressure earn less”?
- We doctors and researchers have understood for quite some time the long-term consequences of excess weight and obesity. We currently recognize that obesity is associated with at least 236 medical diagnoses, including 13 types of cancer. Obesity can decrease one’s lifespan by up to 8 years.
- Despite knowing this, U.S. physicians are not prepared to prevent and reverse obesity. In a recently published survey, only 10% of medical school deans and curriculum experts feel that their students were “very prepared” in regards to obesity management. Half of the medical schools responded that expanding obesity education was a low priority or not a priority. An average of 10 hours total was reported as dedicated to obesity education during their entire training in medical school.
- And doctors sometimes don’t know how or when to prescribe medications for patients with obesity. For example, eight FDA-approved weight loss medications are on the market, but only 2% of eligible patients receive prescriptions for them from their physicians.
What goes on in the body
- So, here we are, with a collision of the obesity epidemic and the C19 pandemic. And a question I find patients asking me more and more: How does obesity create more severe disease and complication from C19 infection?
- There are many answers; lets start with structure.
- Excess adipose tissue, which stores fat, creates a mechanical compression in patients with obesity. This limits their ability to take in and completely release a full breath of air.
- Breathing takes more work in a patient with obesity. It creates restrictive lung disease, and in the more serious cases, lead to hypoventilation syndrome, which can cause a person to have too little oxygen in their blood.
- And then there is function. Obesity results in an excess of adipose tissue, or what we colloquially call “fat.” Over the years, scientists have learned that adipose tissue is harmful in and of itself. One may say that adipose tissue acts as an endocrine organ all its own. It releases multiple hormones and molecules that lead to a chronic state of inflammation in patients with obesity.
- When the body is in a constant state of low-grade inflammation, it releases cytokines, proteins that fight inflammation. They keep the body on guard, simmering and ready to fight disease. That’s all well and good when they are kept in check by other systems and cells. When they are chronically released, however, an imbalance can occur that causes injury to the body. Think of it like a small but contained wildfire. It’s dangerous, but it’s not burning the entire forest.
- C19 causes the body to create another cytokine wildfire. When a person who is obese has C19, two small cytokine wildfires come together, leading to the raging fire of inflammation that damages the lungs even more so than patients with normal BMI.
- Additionally, this chronic state of inflammation can lead to something called endothelial dysfunction. In this condition, instead of opening up, blood vessels close down and constrict, further decreasing oxygen to the tissues.
- In addition, increased adipose tissue may have more ACE-2, the enzyme that allows the coronavirus to invade cells and begin to damage them. A recent study has shown an association of increased ACE-2 in adipose tissue rather than lung tissue. This finding further strengthens the hypothesis that obesity plays a major role in more serious C19 infections. So in theory, if you have more adipose tissue, the virus can bind to and invade more cells, causing higher viral loads that stay around longer, which can make the infection more severe and prolong recovery.
- ACE-2 can be helpful in counteracting inflammation, but if it otherwise bound to C19, it cannot assist with this.
- The novel SARS C19 virus has forced the medical profession to face the reality that many U.S. physicians inherently know. When it comes to prevention of chronic diseases such as obesity, the U.S. health care system is not performing well. Many insurers reward physicians by meeting metrics of treating the effects of obesity rather than preventing it or treating the disease itself. Physicians are reimbursed, for example, for helping patients with Type 2 diabetes to attain a certain A1C level, or a set blood pressure goal.
- I believe is time to educate physicians and provide them with resources to combat obesity. Physicians can no longer deny that obesity, one of the strongest predictors for C19 and at least 236 other medical conditions, must become public enemy number one.
7. Damage to multiple organs recorded in ‘long Covid’ cases
- Young and previously healthy people with ongoing symptoms of C19 are showing signs of damage to multiple organs four months after the initial infection, a study suggests.
- The findings are a step towards unpicking the physical underpinnings and developing treatments for some of the strange and extensive symptoms experienced by people with “long Covid”, which is thought to affect more than 60,000 people in the UK. Fatigue, brain fog, breathlessness and pain are among the most frequently reported effects.
- On Sunday, the NHS announced it would launch a network of more than 40 long Covid specialist clinics where doctors, nurses and therapists will assess patients’ physical and psychological symptoms.
- The Coverscan study aims to assess the long-term impact of C19 on organ health in around 500 “low-risk” individuals – those who are relatively young and without any major underlying health complaints – with ongoing Covid symptoms, through a combination of MRI scans, blood tests, physical measurements and online questionnaires.
- Preliminary data from the first 200 patients to undergo screening suggests that almost 70% have impairments in one or more organs, including the heart, lungs, liver and pancreas, four months after their initial illness.
- “The good news is that the impairment is mild, but even with a conservative lens, there is some impairment, and in 25% of people it affects two or more organs,” said Amitava Banerjee, a cardiologist and associate professor of clinical data science at University College London.
- “This is of interest because we need to know if [the impairments] continue or improve – or if there is a subgroup of people who could get worse.”
- In some, but not all, cases there was a correlation between people’s symptoms and the site of the organ impairment. For instance, heart or lung impairments correlated with breathlessness, while liver or pancreas impairments were associated with gastrointestinal symptoms.
- “It supports the idea that there is an insult at organ level, and potentially multi-organ level, which is detectable, and which could help to explain at least some of the symptoms and the trajectory of the disease,” said Banerjee.
- However, the study doesn’t prove that organ impairments are the cause of people’s ongoing symptoms, and the data haven’t yet been peer-reviewed.
- Banerjee also cautioned that none of the patients were scanned before developing C19, so some of them may have had existing impairments – although this is unlikely given their previous good health and relative youth. The average age of participants was 44.
- They will continue to be monitored, and the researchers are also scanning people who haven’t had C19 or have experienced other viral infections such as flu, for comparison.
- Preliminary data from a separate study of 58 patients who were hospitalized with C19 similarly found abnormalities in the lungs of 60%; in the kidneys of 29%; in the hearts of 26%; and in the livers of 10% of patients, two to three months after the initial infection, as well as tissue changes in parts of the brain.
- “What all the people in the world with long Covid are crying out for is to be taken seriously and to have some idea of what might be going on at the organ level – so to begin to assemble some kind of evidence base is absolutely the way to go,” said Danny Altmann, a professor of immunology at Imperial College London.
- “I think this is a first step in a long journey towards providing some kind of mechanism [for their symptoms], and eventually some therapeutics for people with long Covid.”
- The new findings could also have implications for the management of people with long Covid, suggesting the need for closer collaboration between medical specialists. “Sending the people you need to the cardiologist, and then to the gastroenterologist, and then to the neurologist would be an inefficient way to deal with things as the pandemic continues,” Banerjee said.
G. The Road Back?
1. Restaurants are C19 hotpots. How to make them safer?
A new model that used smartphone data to monitor infection spread found that limiting public venues to 20% of capacity would cut infections by 80%.
- During this pandemic, every activity in an indoor public place involves some level of risk, but some venues are far riskier than others—especially if they’re small and crowded.
- We already knew that restaurants can easily become covid hot spots, but a new paper published in Nature today quantifies just how dangerous they really are: four times riskier than the next riskiest location, which was the gym. However, there could be a simple way to reduce the danger. Caps on the number of people permitted to be inside a restaurant simultaneously could cut infections drastically, according to a new model created by the team of epidemiologists, computer scientists, and social scientists from Stanford and Northwestern universities.
- The researchers used smartphone data to predict where people were catching the coronavirus. They used data on the movements of almost 100 million people in the 10 biggest cities in the US from March 1 to May 1, 2020, provided by SafeGraph, a company that aggregates anonymized location data from smartphone apps. They collected the movements of people between their neighborhoods and points of interest like gyms, grocery stores, restaurants, or places of worship.
- Then they used the smartphone data to predict infections on the basis of three metrics: how big the venue was, how long people stayed inside it, and how many people were likely to be infectious in the given area. Finally, they compared their model’s predicted number of infections with the official number of infections recorded in those neighborhoods over that same period. The new model was able to accurately predict actual cases, the team said.
- By simulating various scenarios using the model (full capacity reopening, or caps at 50%, for example), the researchers found that implementing occupancy caps of 20% of capacity would cut infection rates by 80% while minimizing the economic impact. The study found that just 10% of locations accounted for 85% of infections in Chicago in the time period examined—likely down to so-called superspreading events. This suggests that occupancy caps could significantly cut transmission rates, while allowing businesses to stay open. Since these caps would mostly only impact visits during peak hours, restaurants would lose about 42% of customers on average. The authors emphasized that measures like mask-wearing and social distancing would also have to be part of the mix to reopen safely.
- “Our work highlights that it doesn’t have to be all or nothing, and we can choose different methods for different places,” said Jure Leskovec, an associate professor of computer science at Stanford University and one of the paper’s authors, at a press conference today. “Our work provides a tool for policymakers to navigate the tradeoffs.” [NOTE: The study did not indicate whether or not restaurant owners would be able to operate with 42% fewer customers.]
- The study also shed some more light on exactly why your risk of catching, and dying from, C19 correlates so closely with your ethnicity and socioeconomic background. First, the model found that people in neighborhoods with fewer white people and lower average incomes do not have as much opportunity to reduce their mobility, no doubt because they’re less likely to have jobs they can do from home. Not only that, but the places that lower-income groups visit tend to be more crowded, which increases the risk of infection. The study found that the grocery stores frequented by people with lower incomes are typically more tightly packed and shoppers tend to stay inside for longer, making these visits twice as dangerous.
- There is an obvious drawback to occupancy caps: they reduce the amount of money businesses can pull in, potentially to the point where they become economically unviable. Working out how businesses make enough money to stay open while capping how many people can visit them, or whether the government should subsidize businesses to keep them afloat with restricted customer numbers, is the next complex and contentious issue to tackle. Over to you, economists.
2. Outdoor Dining Tents Raise Questions of Virus Safety as Winter Nears
- As temperatures cool, many of the outside dining options that have sprung up across the U.S. in reaction to pandemic restrictions have become a little less open-air.
- The new structures come in varying forms, from clear plastic tents that allow just a few people to eat together to what appear to be full-on cabins inhabiting former parking spaces. Restaurants hope they’ll keep out the winter chill while keeping the virus at bay. That could allow them to serve more diners amid rules that dictate reduced capacity inside.
- The problem: “Some of them are clearly not safe,” said Jack Caravanos, a clinical professor at New York University’s School of Global Public Health and an industrial hygienist whose work assesses the safety of indoor and outdoor environments. “It is sort of the Wild West out there with the creation of these structures.”
- Linsey Marr, an engineer who studies the airborne transmission of viruses at Virginia Tech, said the reality is that the safety of these spaces lies somewhere between those of full-on outside dining and going back indoors. “You still should follow all the protocols from indoors,” Marr said of the tent spaces. “People should be distanced, I would prefer to see tables 10 feet apart. People should be wearing masks when they’re not eating.”
A restaurant’s outdoor eating space on the street in New York.
- Think about it as if you’re sitting near someone smoking a cigarette. The more air circulation there is, the less likely you are to be bothered by the smell of a nearby smoker. The more enclosed the space, the more likely it is that smoke will hang in the air. The same is true of the airborne respiratory droplets and particles that can carry the virus.
- Marr said she would only risk dining in these more enclosed tent spaces if the conditions were right. “If nobody else was there — or there were very, very few other people there — I might do it,” she said. “And I wouldn’t do it with people outside my household.”
- In New York, where sidewalk dining was such a hit the city decided to make it permanent, regulations for tents depend on how enclosed the structures are. Partial tent enclosures, where at least half of the tent’s sidewall surface area is open, are regulated the same as any outdoor dining, the idea being that with so much open space, air can easily circulate through. Fuller tent enclosures, though, face the same capacity limitations as indoor dining, with a state-mandated 25% occupancy maximum.
- In those cases, restaurants must also follow stricter procedures for indoor dining, such as checking the temperature of diners. Restaurants must apply for permits for outdoor dining, but no additional permits are required for tents.
- One-third to one-half of New York City’s restaurants and bars could shut down within the next six months to a year, according to estimates cited in an October report by New York State Comptroller Thomas DiNapoli. In the meantime, the outside venues have been a needed lifeline for the city’s eateries, the New York mayor’s office said in a statement. More than 10,000 restaurants have participated in the outdoor dining program.
- “Of course, New Yorkers should decide what’s right for them before they dine — but we’re confident that current rules strike the right balance between supporting small businesses and fighting back C19,” said Mitch Schwartz, deputy press secretary at the mayor’s office.
Dining on Mission Street in San Francisco.
- But rates are surging across the country, hitting record numbers of more than 130,000 new cases a day. Those rates may grow even more as the weather cools, spurring even more people to gather together indoors. All this raises new questions about these hybrid indoor-outdoor spaces. New York Mayor Bill de Blasio has previously said that the city should halt indoor dining if the seven-day positivity rate surpassed 2%. That threshold has already been crossed, but despite calls to end indoor dining until rates recede, the city has so far moved only to ban it after 10 p.m.
- “We’re all hoping that we’ll have a mild winter, with some warm days where people are still comfortable eating outdoors,” said Andrew Rigie, executive director of the NYC Hospitality Alliance, which represents nearly 3,000 restaurants in the five boroughs and has called for increasing indoor dining occupancy, to 50% of capacity from 25%. “But the reality is, New York City winters get really cold. And people are not going to sit outside and dine in the freezing cold and snow.”
Plastic “house” tents in New York’s Upper West Side.
- In addition to tent setups that can, at times, be elaborate, restaurants have begun adding outdoor heaters and telling diners to “BYOB” — bring your own blanket. Some even give out the type of foil blankets used after a marathon, Rigie said. At least one restaurant has offered blankets for $4 a pop.
- While restrictions vary among cities and states on what forms of dining are allowed, many locations have chosen to treat enclosed tents differently than more al fresco options. In Illinois, where indoor dining shut down across the state as levels of the virus surged, outdoor tents have become crucial for restaurants. Chicago requires that at least half of the sides stay open.
- Some eateries in Chicago’s Fulton Market district have set up clear, enclosed pods known as igloos on a shut-down street. The pods need to have some ventilation, seat six people or fewer at a table, and be sanitized between parties, said Sam Toia, president and chief executive officer of the Illinois Restaurant Association.
People dine in igloo pods outside a restaurant in New York.
- In Connecticut, such pods were briefly off-limits. New guidelines now allow them alongside such measures as adequate ventilation and signs telling customers that enclosed spaces carry higher risks, the Connecticut Restaurant Association said last week.
- NYU’s Caravanos said he’s watched with concern the rise of more enclosed outdoor dining spaces, including one being built near his university that “literally looks like a huge outdoor restaurant made of plywood.”
- But restaurant patrons can take steps to protect themselves, something he and his wife did at dinner just the other week. At a pub with a semi-enclosed outdoor setup, they eschewed a corner seat for a big table by the entrance, Caravanos said. “It’s all about risk assessment,” he said.
3. How the Swiss Cheese Model Can Help Us Beat C19
- In hopeful news this week, Pfizer and its partner, BioNTech, released interim results from an ongoing trial of their candidate coronavirus vaccine. The study involved 43,538 volunteers who were randomly assigned either the vaccine or a placebo. The rates of infection were small for both groups, but those who got the placebo were substantially more likely to get C19 (85 or more cases) than those who got the treatment (just 9 cases or fewer). This is a terrific development, but it should be noted that even among those who got the vaccine, the infection rate was not zero.
- It’s important to understand that a vaccine, on its own, won’t be enough to rapidly extinguish a pandemic as pernicious as C19. The pandemic cannot be stopped through just one intervention, because even vaccines are imperfect. Once introduced into the human population, viruses continue to circulate among us for a long time. Furthermore, it’s likely to be as long as a year before a C19 vaccine is in widespread use, given inevitable difficulties with manufacturing, distribution and public acceptance.
- Controlling C19 will take a good deal more than a vaccine. For at least another year, the U.S. will have to rely on a multipronged approach, one that goes beyond simplistic bromides and all-or-nothing responses. Individuals, workplaces and governments will need to consider a diverse and sometimes disruptive range of interventions. It helps to think of these in terms of layers of defense, with each layer providing a barrier that isn’t fully impervious, like slices of Swiss cheese in a stack.
- The ‘Swiss cheese model’ is a classic way to conceptualize dealing with a hazard that involves a mixture of human, technological and natural elements.
- The British psychologist James Reason introduced the model more than three decades ago to discuss failures in complex systems such as nuclear power, commercial aviation and medical care. As Prof. Reason argued, “In an ideal world each defensive layer would be intact. In reality, however, they are more like slices of Swiss cheese, having many holes…. The presence of holes in any one ‘slice’ does not normally cause a bad outcome. Usually, this can happen only when the holes in many layers…line up…bringing hazards into damaging contact with victims.”
- This is also an invaluable way to think about the response to C19. Last month, a graphic illustrating the model (see image below), sketched by the Australian virologist Ian MacKay, became an online sensation among C19 watchers. It showed particles of the the coronavirus (SARS-CoV-2) passing through layers of Swiss cheese, shrinking in numbers as they negotiated the holes and finally being stopped at the end.
- The main non-pharmaceutical tools available to us in responding to a deadly circulating virus come in two broad categories. At the individual level, the interventions include washing hands, wearing masks and self-isolation. By definition, these actions involve a certain amount of personal agency. Though some Americans have been punished in recent months for flouting such rules, individuals usually have some control over how much they implement them and in what settings.
- But there is only so much that individuals acting on their own can achieve, no matter how much they wash their hands, wear masks and maintain physical distance. Collective interventions are also needed to stem the spread of a deadly infectious disease. Such actions are usually coordinated and mandated by governments. They involve and affect everyone, though they may not be to everyone’s liking.
- These policies include disinfecting public spaces, closing borders, restricting movements, shutting schools, banning gatherings, closing businesses, instituting testing and contact tracing, quarantine of exposed individuals and issuing “stay at home” orders. Because these sorts of interventions often impose very real hardships on citizens who remain (or at least appear) uninfected, they can provoke resentment and even resistance.
- Another way to think about these various interventions, individual and collective, is with respect to how they operate as barriers to the spread of the disease. Some—like wearing a mask, hand-washing, sanitizing public places or deploying Plexiglas barriers—achieve their effect by reducing transmission of the pathogen. Others—like self-isolation, quarantine and school closures—work by modifying the pattern of human interactions to deprive the pathogen of opportunities to spread. They reduce social contact.
- These various approaches—whether individual or collective, whether aimed at reducing transmission or contact—are not mutually exclusive. In fact, they often have complementary strengths and weaknesses. And they work best in combination, like using both chemotherapy and radiation to treat cancer or combining exercise and diet to prevent heart disease.
- Each layer of defense can reduce the impact of the virus. We know that, after stacking two slices of “Swiss cheese,” it might still be possible to look through the two pieces through a hole that happens to line up across the two slices. But after stacking, say, four slices, the random holes are much less likely to align.
- Of course, some layers—such as testing, masking and a good vaccine—are more effective than others, such as sanitizing surfaces. These are the Swiss cheese slices with fewer or smaller holes. But no single intervention is enough. Even after a vaccine is widely available, other interventions will still be needed, at least for a while.
- One analysis of data from 11 European countries found that even lockdowns, which are highly effective, were not perfect; they reduced SARS-CoV-2 transmission by 81%. Another analysis of 13 European countries found that intercity travel restrictions, canceling public events and closing nonessential workplaces had meaningful impacts on the death rates for the virus (closing schools and imposing stay-at-home rules showed smaller effects). An analysis of early stages of the pandemic in China found that detecting and isolating cases was more effective than travel restrictions, but combinations of approaches were optimal.
- The Swiss cheese model can thus show us a path forward for sensible, science-based policies at the local and national level.
- First, it’s clear that, in order to stop the spread of the virus and deflect the course of the pandemic, we need to think in terms of deploying enough layers of Swiss cheese. In any setting, it’s more important to choose several interventions than any particular one. No matter the specific combination, so long as a certain threshold is achieved, the epidemic can be controlled. Usually, that will mean a combination of actions designed to reduce transmission and to limit contact. But to succeed, a person, family, business or nation must adopt several different measures, not just one or two.
- The Swiss cheese model also helps to explain how and why different countries have succeeded using different approaches. South Korea relied on mask-wearing and testing on a very wide scale; New Zealand closed its borders and did extensive contact tracing; Greece banned gatherings and closed schools. These were the key layers of their defense against the virus, to which they added several others. Places that have not deployed enough layers of defense, like many areas of the U.S. now experiencing skyrocketing caseloads, need to do more if they hope to contain the spread of C19 and avoid more deaths.
- Finally, the Swiss cheese model highlights how we might avoid relying on some of the more disruptive and controversial Covid-fighting measures, such as stay-at-home orders and school closures. If several layers of defense are already in place and holding strong, additional layers might be unnecessary to close gaps.
- It’s important to recognize that the virus itself often compels many of these measures. In centuries past, during outbreaks of bubonic plague, people engaged in physical distancing without being ordered to do so. Economic collapse and social disarray have been features of epidemics for centuries. As the historian and priest John of Ephesus noted over 1,500 years ago, during the Plague of Justinian: “Buying and selling ceased and the shops with all their worldly riches beyond description and moneylenders’ large shops closed. The entire city then came to a standstill as if it had perished.”
H. Innovation & Technology
1. The Hot New Covid Tech Is Wearable and Constantly Tracks You
- In Rochester, Mich., Oakland University is preparing to hand out wearable devices to students that log skin temperature once a minute — or more than 1,400 times per day — in the hopes of pinpointing early signs of the coronavirus.
- In Plano, Texas, employees at the headquarters of Rent-A-Center recently started wearing proximity detectors that log their close contacts with one another and can be used to alert them to possible virus exposure.
- And in Knoxville, students on the University of Tennessee football team tuck proximity trackers under their shoulder pads during games — allowing the team’s medical director to trace which players may have spent more than 15 minutes near a teammate or an opposing player.
- The powerful new surveillance systems, wearable devices that continuously monitor users, are the latest high-tech gadgets to emerge in the battle to hinder the coronavirus. Some sports leagues, factories and nursing homes have already deployed them. Resorts are rushing to adopt them. A few schools are preparing to try them. And the conference industry is eyeing them as a potential tool to help reopen convention centers.
- “Everyone is in the early stages of this,” said Laura Becker, a research manager focusing on employee experience at the International Data Corporation, a market research firm. “If it works, the market could be huge because everyone wants to get back to some sense of normalcy.”
- Companies and industry analysts say the wearable trackers fill an important gap in pandemic safety. Many employers and colleges have adopted virus screening tools like symptom-checking apps and temperature-scanning cameras. But they are not designed to catch the estimated 40% of people with C19 infections who may never develop symptoms like fevers.
- Some offices have also adopted smartphone virus-tracing apps that detect users’ proximity. But the new wearable trackers serve a different audience: workplaces like factories where workers cannot bring their phones, or sports teams whose athletes spend time close together.
- This spring, when coronavirus infections began to spike, many professional football and basketball teams in the United States were already using sports performance monitoring technology from Kinexon, a company in Munich whose wearable sensors track data like an athlete’s speed and distance. The company quickly adapted its devices for the pandemic, introducing SafeZone, a system that logs close contacts between players or coaches and emits a warning light if they get within six feet. The National Football League began requiring players, coaches and staff to wear the trackers in September.
- The data has helped trace the contacts of about 140 N.F.L. players and personnel who have tested positive since September, including an outbreak among the Tennessee Titans, said Dr. Thom Mayer, the medical director of the N.F.L. Players Association. The system is particularly helpful in ruling out people who spent less than 15 minutes near infected colleagues, he added.
- College football teams in the Southeastern Conference also use Kinexon trackers. Dr. Chris Klenck, the head team physician at the University of Tennessee, said the proximity data helped teams understand when the athletes spent more than 15 minutes close together. They discovered it was rarely on the field during games, but often on the sideline.
- “We’re able to tabulate that data, and from that information we can help identify people who are close contacts to someone who’s positive,” Dr. Klenck said.
- Civil rights and privacy experts warn that the spread of such wearable continuous-monitoring devices could lead to new forms of surveillance that outlast the pandemic — ushering into the real world the same kind of extensive tracking that companies like Facebook and Google have instituted online.
- They also caution that some wearable sensors could enable employers, colleges or law enforcement agencies to reconstruct people’s locations or social networks, chilling their ability to meet and speak freely. And they say these data-mining risks could disproportionately affect certain workers or students, like undocumented immigrants or political activists.
- “It’s chilling that these invasive and unproven devices could become a condition for keeping our jobs, attending school or taking part in public life,” said Albert Fox Cahn, executive director of the Surveillance Technology Oversight Project, a nonprofit in Manhattan. “Even worse, there’s nothing to stop police or ICE from requiring schools and employers to hand over this data.”
- Executives at Kinexon and other companies that market the wearable trackers said in recent interviews that they had thought deeply about the novel data-mining risks and had taken steps to mitigate them.
- Devices from Microshare, a workplace analytics company that makes proximity detection sensors, use Bluetooth technology to detect and log people wearing the trackers who come into close contact with one another for more than 10 or 15 minutes. But the system does not continuously monitor users’ locations, said Ron Rock, the chief executive of Microshare. And it uses ID codes, not employees’ real names, to log close contacts.
- Mr. Rock added that the system was designed for human resources managers or security officials at client companies to use to identify and alert employees who spent time near an infected person, not to map workers’ social connections.
- GlaxoSmithKline, the pharmaceutical giant, recently began working with Microshare to develop a virus-tracing system for its sites that make over-the-counter drugs. Budaja Lim, head of digital supply chain technology for Asia Pacific at the company’s consumer health care division, said he wanted to ensure maximum privacy for workers who would wear the proximity detection sensors.
- As a result, he said, the system silos the data it collects. It logs close contacts between workers using ID numbers, he said. And it separately records the ID numbers of workers who spent time in certain locations — like a packaging station in a warehouse — enabling the company to hyper-clean specific areas where an infected person may have spent time.
- GlaxoSmithKline recently tested the system at a site in Malaysia and is rolling it out to other consumer health plants in Africa, Asia and Europe. The tracking data has also allowed the company to see where workers seem to be spending an unusual amount of time close together, like a security desk, and modify procedures to improve social distancing, Mr. Lim said.
- “It was really designed to be a reactive type of solution” to trace workers with possible virus exposure, he said. “But it has actually become a really powerful tool to proactively manage and protect our employee safety.”
- Oakland University, a public research university near Detroit, is at the forefront of schools and companies preparing to making the leap to the BioButton, a novel coin-size sensor attached to the skin 24/7 that uses algorithms to try to detect possible signs of C19.
- Whether such continuous surveillance of students, a young and largely healthy population, is beneficial is not yet known. Researchers are only in the early phases of studying whether wearable technology could help flag signs of the disease.
- David A. Stone, vice president for research at Oakland University, said school officials had carefully vetted the BioButton and concluded it was a low-risk device that, added to measures like social distancing and mask wearing, might help hinder the spread of the virus. The technology will alert campus health services to students with possible virus symptoms, he said, but the school will not receive specific data like their temperature readings.
- “In an ideal world, we would love to be able to wait until this is an F.D.A.-approved diagnostic,” Dr. Stone said. But, he added, “nothing about this pandemic has been in an ideal world.”
- Dr. James Mault, chief executive of BioIntelliSense, the start-up behind the BioButton, said students with privacy concerns could ask to have their personal details stripped from the company’s records. He added that BioIntelliSense was preparing to conduct a large-scale study examining its system’s effectiveness for C19.
- Oakland had initially planned to require athletes and dorm residents to wear the BioButton. But the university reversed course this summer after nearly 2,500 students and staff members signed a petition objecting to the policy. The tracker will now be optional for students.
- “A lot of colleges are doing masks and social distancing,” said Tyler Dixon, a senior at the school who started the petition, “but this seemed like one step too far.”
I. Practical Tips & Other Information
1. Pre-Thanksgiving Screening Test For C19 Won’t Keep You Safe
- THE PLAN SOUNDS so reasonable on its face: We’ll all get together for Thanksgiving, but only after everyone—every last member of the family, no matter where they’re coming from or how they’ll get there—has had the chance to get a proper Covid test.
- It isn’t only for the holidays. For months now, I’ve watched various acquaintances and their families decide to break the rules of social distancing in accordance with this same and suspect rule of thumb: It’s totally OK to meet up for a weekend trip … as long as everyone has gotten tested; it’s fine to get together for a barbecue, or a visit with Grandma … just as soon as everyone has gotten tested.
- Let me put this as clearly as I can: As a means of eliminating risk in the midst of a pandemic, the everyone-has-gotten-tested method is utterly absurd.
- It’s true that getting a positive result tells you some crucial information: It’s time to cancel all your plans and isolate until you’re past the point of infectiousness. A negative test, though, doesn’t guarantee that anyone is Covid-free, and it’s never license to let down your guard. You might, for instance, contract the virus in the interim between being tested and receiving your results, or between getting your results and seeing your friends and family. (The testing site itself could even be where that happens.) Even if you assume these tests are 100 percent accurate, they’ll only tell you what your status is at the specific time the test is done.
- Of course, the tests are not 100% accurate. In practice, their error rates may be even higher than the chance that you’re infected in the first place. The probability that you’ll receive a wrong result on any medical test depends not just on the test’s innate accuracy but on your baseline risk. Even a very good test will turn out more false positives than real ones if you go in as someone who isn’t likely to have the disease. Conversely, getting a negative result won’t give you that much information you didn’t have before. It might only increase your confidence at the margins, say from 95 to 98 percent, that you’re not already sick.
- Covid testing is important, as a rule—it’s how we can identify people who have the coronavirus so they can separate themselves and stop the chains of transmission. Where people are coming together repeatedly in shared spaces, as in schools and workplaces or on sports teams, frequent testing can reduce transmission and outbreaks—but only when it’s paired with a robust system for isolation and contact tracing.
- As I’ve written here previously, testing alone isn’t enough; for disease surveillance to make a difference, it must be used alongside behavioral interventions such as masking and social distancing. If you’re assuming that a negative test means you can give up on those behaviors—that you can safely gather for dinner at a grandparent’s house or spend a weekend in a cabin with your buddies—then you’re asking for trouble.
- The everyone-gets-tested strategy makes a bit more sense if you think of it as a form of risk reduction, rather than a guarantee of safety. But even framed that way, it doesn’t make a ton of sense. Life in the pandemic requires making tradeoffs, and you may well decide that getting together with loved ones is worth whatever dangers it may bring. But if you really want to mitigate that danger, you should focus on what works best—and universal, one-off screening within your friend group isn’t it.
- The best approach, says Kilpatrick, would be for everyone to go into full quarantine (that means no grocery shopping or other interactions with people) for two weeks prior to the visit, and then travel by car without coming into close contact with anyone else along the way. He acknowledges that this obviously isn’t going to be practical for most people. Short of that, you and your loved ones might each agree to go into full quarantine for several days—which is better than nothing—while continuing to practice masking and social distancing as much as possible.
- If you can all add a test on top of that, so much the better. According to Gretchen Snoeyenbos Newman, an infectious disease physician at Wayne State University, the best time for screening tests would be five to seven days after your last contact with someone outside your household. (Others have proposed a strict, eight-day quarantine with a Covid test at the tail end of it. Either way, this approach still involves a lot of time in isolation.) But, again, any such strategy requires a lot of assumptions—that getting tested does not itself put you in contact with people who are infected, and that it’s locally available for people without symptoms, and that you’ll get your results in a reasonable amount of time. Otherwise, you may as well not bother.
- Instead of relying on a test to give you a green light, it’s better to do all you can to avoid exposures in the first place. With Covid cases climbing fast, and vaccines that may become available in early 2021, the stakes are even higher than they were before. Canceling Thanksgiving with Grandma means you all miss that human contact this year, but it might also ensure that she’s around for the next family gathering.
2. The One Time During a Flight that It’s Not Safe to Take off Your Mask: Deicing
- Airlines and aircraft manufacturers have touted the robust ventilation in cabins, with the constant introduction of fresh air from outside the plane, as protection for passengers against virus transmission. But travelers should be aware of the one time in many trips when airflow is reduced: deicing.
- The process, which usually takes 10 to 20 minutes, is essential for takeoffs in wintry weather. As deicing fluid is sprayed on jets, outside air is shut off so fumes and fluid don’t get into jets. Air inside the cabin continues to recirculate and pass through hospital-grade filters capable of capturing viruses. Airlines and aircraft manufacturers say it’s safe for passengers during deicing; public health experts who have studied airline cabin conditions generally agree.
- But aircraft manufacturers confirm the flow of air is reduced by as much as 50%. Airbus and Boeing have recently issued new guidance to airlines about how to handle cabin airflow during deicing.
- As winter approaches, fliers can help themselves and fellow passengers by making sure they have masks on when they hear the deicing process start. It’s not the time to be sipping coffee.
- Aircraft manufacturers have told airlines to make sure pilots set cabin air recirculation at the highest level possible during deicing. Outside air is shut off when airplanes are sprayed, and airflow is reduced even when at maximum settings.
- On Friday, Boeing issued a memorandum to airlines recommending that air recirculation remain switched on during deicing. Boeing had previously told airlines that recirculation was optional.
- The company says the volume of cabin air is exchanged every three to six minutes during deicing on its planes instead of the standard exchange rate of every two to three minutes. That’s still significantly faster than most hospitals and airports, Boeing says. The company says it’s continuing to discuss cabin airflow and deicing with airlines.
- Likewise, Airbus issued a recommendation to airlines as part of C19 precautions that airflow during deicing be switched to high, the strongest of three airflow settings its jets offer, along with low and normal. Airbus spokesman Clay McConnell says the manufacturer hadn’t previously made a recommendation of airflow settings during deicing.
- “During deicing, the airflow is slightly reduced in the cabin, but the majority of the airflow remains the same. It doesn’t have a substantial reduction in the sort of protection that passengers would have,” Mr. McConnell says. He lists masks and cabin cleaning as other factors that protect passengers. (Other research has raised questions about the safety of some chemicals used during cabin cleaning.)
- Deicing removes snow, ice or frost from aircraft surfaces before takeoff. A large number of flights can be affected, especially in colder cities. United says 12.5% of all its January departures required deicing. For all of 2019, the total was 4% of United flights.
- Depending on how fast precipitation falls, how cold it is and what kind of fluid is used, jets have a relatively short window to take off after deicing—often no more than 30 minutes. So spraying fluid must take place with everyone onboard. At some airports that can happen at the gate, but typically jets taxi to a remote area where spraying trucks are set up and deicing fluid is collected because of environmental concerns.
- Airlines say they are confident cabins are safe. Some also say they are studying the issue and looking for any changes to deicing procedures that might avoid any reductions in airflow.
- “We continue to work with aircraft manufacturers to find solutions that enable us to maintain stronger airflow while the aircraft undergoes deicing,” United spokesman Charles Hobart says.
- Ventilation, air filtering and masks have been the main reasons that few cases of coronavirus transmission have been traced to time aboard airplanes, though tracing is spotty at best in many places, including the U.S. One reassurance: Airlines and flight attendant unions say flight attendants have tested positive at the same or lower rates as airline employees who work on the ground.
- An October study from Harvard University’s School of Public Health using mathematical models found a low risk of coronavirus transmission on airplanes because of a layered approach, including aircraft ventilation and masks. Ventilation systems quickly remove aerosol particles people expel breathing and talking, Harvard researchers said. That, along with masks, reduce risk when people are in proximity onboard, they said. (The research was supported financially by airlines, aircraft manufacturers and airports. Harvard says contracts required independence of research.)
- The Harvard recommendations included extending “in-flight level of ventilation while on the ground.” Asked whether the reduction in ventilation during deicing is a concern, Jack Spengler, professor of environmental health and human habitation and a leader of the Harvard team, says researchers are working on that question.
- “While we are reviewing existing data made available to us from airplane manufacturers, we are also conducting an independent review through our own models in order to make a recommendation regarding ventilation and other potential strategies for the deicing process,” Dr. Spengler says.
- Studies on outbreaks of previous viruses found that how close people were to an infected person on an airplane did make a difference in whether they contracted the virus. Generally two rows on either side of an infected passenger were considered the hot zone.
- Howard Weiss, a Penn State University biology professor and one of the authors of a 2018 study identifying transmission paths for respiratory diseases on airplanes, says the airflow reported during deicing, while reduced, should still be adequate to reduce airborne transmission.
- Still, close contact with a person infected with C19 is a concern on airplanes. He notes the CDC’s updated guidance on Oct. 28 to say, “Available data indicate that it is much more common for the virus that causes C19 to spread through close contact with a person who has C19” and emits larger respiratory droplets through coughing, sneezing, singing, talking or breathing rather than small exhaled particles that can travel more than 6 feet and linger in the air for minutes or even hours.
- Manufacturers say airplane ventilation systems whisk away small airborne particles with the strong ceiling-to-floor air current, but health experts worry they may have a harder time intercepting larger droplets, especially if airflow is reduced.
- Mark Gendreau, chief medical officer at Beverly Hospital in Massachusetts and an expert on disease transmission on airplanes, says you should wear a mask and not eat or drink not only during the deicing but also for an extra 15 minutes after deicing is completed “to give the ventilation system several full air exchanges.”
- That’s important, Dr. Gendreau says, “given most air carriers are announcing they are not going to block the middle seat starting this December and January.”
3. Covid Winter Is Coming. Humidifiers Can Help.
- BY NOW, YOU’VE probably got your coronavirus risk-minimizing routine down pat. Mask? Check. Social distance? Acquired. Spending time indoors with people outside your pod? Hard pass. You wash your hands. (But maybe not your groceries.) And that’s great. Keep it up. Because with the virus now surging to record levels in nearly every state, and hospitals starting to buckle under the strain, doing all these things is more important than ever. But as public health experts warn of a long and deadly winter ahead, there’s one more thing some scientists say we should be talking about: humidity.
- With winter comes plummeting temperatures, and the colder the air gets, the less water vapor it can hold. The way most buildings are heated only exacerbates the problem. Heating, ventilation, and air-conditioning (HVAC) systems suck in outside air and then heat it up, which zaps even more moisture out of it. These changes not only make it easier for respiratory viruses to hop from host to host, but dry air cripples the first few lines of defense your body has for preventing such viruses from establishing an infection. All of this could be a recipe for the coronavirus to wreak even more havoc in the coming months.
- “A lot of indoor environments are bone-dry in the wintertime,” says Jeffrey Shaman, an infectious disease forecaster at Columbia’s Mailman School of Public Health. “That makes the virus more transmissible. And people are spending more time indoors. So a lot of factors are going to be working against us.”
- A decade ago, a team of researchers led by Shaman looked at 31 years’ worth of data on influenza-like illness and weather patterns in the US. Over and over, they found that the biggest outbreaks happened in the winter when the weather was unusually dry. Lab studies with ferrets and guinea pigs showed similar patterns. The influenza virus spread most readily when the relative humidity inside the animals’ cages fell below 40%. (A typical indoor humidity range in warmer weather is between 40 and 60%.)
- Aerosol scientists who study the flu, like Linsey Marr at Virginia Tech, have helped explain why that might be. In a 2012 study, her group showed that as relative humidity levels dip, the particles that people emit through talking or coughing get smaller and smaller. These particles are made up of mucus, salts, protein, and cell parts—but mostly water. The drier the air around them, the faster that water evaporates. And the smaller the particles get, the longer they can stay in the air, the farther they can travel, and the deeper into the lungs they can be inhaled. Any viruses lurking inside these particles go along for the ride.
- If they land inside a susceptible person’s respiratory tract, that can spell trouble. Of course, the body is equipped with multiple layers of security to protect against would-be invaders. The first line of defense is a physical barrier maintained by the cells that line the nasal passages. Some of these cells secrete mucus—two layers of the slippery, stringy, substance, with two different viscosities. Other cells inside the nose and throat have tiny, anemone-like projections called cilia, which beat in synchrony in the more watery layer. That motion moves the thicker, top layer of mucus like a conveyor belt away from the lungs. This mucosal current catches any viruses or bacteria (or other irritants like pollen and ash) that land on it and sweeps them away to be swallowed or coughed out. But if the air is too dry, these mucus layers dessicate, squishing the cilia and immobilizing them.
- In a 2017 study, researchers at Yale University School of Medicine found that mice housed at 10% relative humidity had a much harder time clearing the influenza virus from their respiratory tracts than mice housed in 50% relative humidity. Their mucosal flow slowed way down, as you can see in a stunning set of videos recently posted to Twitter by the study’s lead author, immunologist Akiko Iwasaki. Without a functioning mucociliary response, the virus successfully spread to the lungs of these mice at higher rates, and the animals got sicker than their counterparts that breathed more moist air.
- Cold, dry air can also impair the second and third tiers of the body’s immune response. If a virus gets past the mucus river, its next aim is to find the cells that line the airway, known as epithelial cells, then get inside them and hijack their molecular machinery to make more copies of itself. From the moment that happens, it’s a race between how fast the virus can replicate and how fast the body can rally its defenses. When infected cells sense they’ve been compromised, they flip hundreds of genes on. Some of these encode the recipes for making weapons of molecular war—scissor-like enzymes for shredding the virus’s genetic code and net-like proteins that tether the virus to the cell’s membrane, preventing it from releasing clones of itself to infect other cells nearby. Some of the genes produce chemical distress signals known as interferons. These molecules recruit immune cells to come and join the fight, and their response is what creates inflammation and flu symptoms—coughing, fever, sore throat.
- “Whether or not you get symptoms really depends on how far the virus gets on its quest,” says Ellen Foxman, an immunobiologist at Yale who did her postdoc in Iwasaki’s lab. She has studied how temperature affects this race between the immune system and viruses that cause the common cold. “Cold temperatures affect the speed at which the immune defenses get turned on. It slows them way down and gives the virus a huge advantage,” she says. Similar effects have been observed in mice housed at low humidity—in very dry conditions, their airway epithelial cells lost the ability to turn on those SOS signaling genes. But exactly how dry air affects the interferon response is still an area of active research.
- In the world’s temperate zones, respiratory bugs ebb and surge with the seasons. Each year, influenza, rhinoviruses, and the endemic common cold-causing coronaviruses retreat as temperatures and humidity rise, only to come roaring back as summer turns to fall. These lab experiments help explain how low humidity is likely driving these seasonal swings. But very few scientists have been able to directly test how big an effect humidity can have on preventing infections among people in the real world. In fact, it’s only been done once.
- In 2016, a group of researchers from the Mayo Clinic led by molecular biologist Chris Pierret worked with a local nursery school to install humidifiers in two of its four identically laid-out classrooms. They let them run from January through March, periodically swabbing samples in each classroom, and then tried to grow any viruses they found. During that period, the scientists didn’t find as much infectious virus in the humidified classrooms, and the students who spent time there called in sick with flu-like symptoms less often than the kids in the non-humidified classrooms.
- Pierret got the idea from some of his work with InSciEd Out, a Mayo-affiliated nonprofit aimed at reforming science education to encourage doing research—not just memorizing facts and figures. One way the organization does that is to partner with schools and help their students and teachers conduct experiments with zebrafish, a model organism commonly studied by developmental biologists.
- A couple of years ago, one Minnesota school went all-in on the idea. Administrators installed fish tanks in classrooms and the school’s high-traffic computer lab. That winter turned out to be especially dry, which got to be a problem for maintaining all that new fish habitat. The dry air was sucking up moisture from wherever it could—including the newly acquired collection of aquaria. One of the teachers called Pierret to tell him how exhausted he was. “I’ve been doing nothing but filling fish tanks every day!” Pierret recalls him saying. It also turned out to be a bad year for respiratory infections.
- The majority of schools in the area reported higher-than-average student absenteeism due to flu symptoms. Only one school didn’t: The one with the fish tanks. “It really stood out,” says Pierret. “That was the hypothesis-driving event for us.” He and his colleagues went on to test that hypothesis in a local nursery school, publishing the results in the journal PLOS One.
- Compelling as the Mayo nursery school study was, says Shaman, it’s difficult to make the leap from that one limited example to saying that humidification could be a game-changer against C19. Scientists still aren’t sure if this new coronavirus will exhibit the same seasonality as other respiratory viruses, like strains of influenza and the viruses that cause the common cold. That’s almost impossible to tell in the first year of a pandemic, when the entire world is susceptible to a new pathogen. It might take a year or two for some degree of immunity to get established, before more subtle factors like climate emerge as playing a bigger role in transmission.
- But people like Stephanie Taylor don’t want to wait that long. A physician and Incite Health Fellow at Harvard Medical School, Taylor is also a distinguished lecturer and member of the Epidemic Task Group at ASHRAE, the American Society for Heating, Refrigerating, and Air-Conditioning Engineers. For years, she’s studied the relationship between indoor air and human health. Taylor is among a group of scientists who think that fine-tuning the humidity inside buildings could save thousands of lives every year. In April, she started an online petition urging the World Health Organization to add relative humidity to its indoor-air standard recommendations. The WHO sets guidance for some indoor air quality issues, such as pollution and mold. But currently, it sets no limits on minimum humidity levels in public buildings. So far, more than 4,500 people have signed the petition.
- This summer, she teamed up with researchers at the Massachusetts Institute of Technology to test her hunch about a connection between C19 and humidity. Together, they pulled in data from 125 countries. In one bucket, they collected information about how different nations had prepared for and responded to the pandemic—annual health care spending, school closures, mask mandates, and other policies aimed at curbing the virus’s spread.
- In another bucket they gathered data about the toll of C19, including confirmed cases. Into the third bucket went environmental data—temperature, humidity, air pressure, precipitation, sunlight, as well as spot measurements taken indoors to corroborate estimates of indoor relative humidity. Then they piped all this data into a machine-learning model and tasked it with finding the strongest connections.
- Taylor says her MIT collaborators were sure the data analysis would turn up some other confounding variables that would disprove her hypothesis about the importance of indoor climate. But after three months of data crunching, they found that the most powerful correlation between national numbers of daily new coronavirus cases and daily C19 deaths was indoor relative humidity. Even controlling for dozens of other factors, the data showed that as indoor relative humidity went up during the summer months in the northern hemisphere, deaths plummeted. In the southern hemisphere, the opposite was true—as humidity fell during those nations’ winter months, deaths began to climb. “It’s so powerful, it’s crazy,” says Taylor.
- That work has not yet been published. But Taylor believes it’s the strongest evidence yet that humidity needs to be as much a part of the conversation about containing C19 as is discussion of ventilation, masks, and hand hygiene. “It’s hard to prioritize one intervention over another; we need all of them,” says Taylor. “Humidifiers aren’t a replacement for masks or social distancing or ventilation.
- But when you have more humidification, it enhances all these other things we’re already doing.” At higher humidities, respiratory particles grow faster and fall to the ground earlier, so there’s a better chance that staying 6 feet apart from infectious people really will dilute how many bits of their aerosolized virus you might happen to inhale.
- In a recent modeling study, Japanese researchers found that air with 30% relative humidity can carry more than twice the number of infectious aerosols, compared to air with relative humidity levels of 60% or higher. That also means masks are more likely to block more of the particles coming out of people’s noses and mouths, because they tend to be better at trapping bigger particles than smaller ones. And it means that air purifiers (even cheap, DIY ones) will filter out a larger proportion of potentially infectious particles.
- We know what you’re thinking: that now, on top of everything else, you’ve got to be measuring and monitoring the amount of moisture in your home! As if the C19 risk mitigation calculus wasn’t complicated enough already. But Pierret says there’s a way to simplify things. “If you could only humidify one space, I’d make it the one where you’re sleeping,” he says, noting that in giving such advice he is speaking for himself and not for the Mayo Clinic.
- In addition to keeping your mucus flowing and your cilia beating, research has shown that people sleep better in rooms with between 40 and 60% relative humidity. And during sleep, your immune system produces antibodies and other important signaling molecules. So the better you sleep, the more ready your body will be to fend off any future infections.
- Still, Pierret says that it’s important not to think of humidification as any sort of magical fix. You still have to wear a mask and wash your hands and stay socially distant and avoid crowded indoor spaces. “Any one of those alone is not enough,” he says. “But each one is like a card that you’re putting into a deck to stack the odds in your favor.”
4. Elastic-free face masks can help some with allergies stay safe during C19
- A University of Cincinnati immunologist is recommending that individuals with contact dermatitis choose facial masks made without elastic or rubber that allow them to stay safe in the midst of C19 while avoiding possible allergic reactions.
- Yashu Dhamija, MD, a first-year fellow in the UC Division of Immunology, Allergy, and Rheumatology, presented his findings in an abstract while discussing a medically challenging case at the virtual American College of Allergy, Asthma and Immunology (ACAAI) scientific meeting held November 13-15.
- “How do you help patients manage a condition that puts them at risk for something like C19?” asked Dhamija. “We definitely want our patients to use masks and apply social distancing. That’s a must. But they can avoid elastic components and use face masks that use the knot tie method around the back of the head to keep the masks up.”
- Dhamija treated a patient who had been diagnosed with contact dermatitis, a reaction to allergens that touch or have contact with the skin. It is different from allergies to things such as dog or cat dander because with contact dermatitis the body’s response is not immediate.”
- “What makes contact dermatitis tricky is that it can be delayed so you may expose your skin to something and a reaction may not occur until days later,” said Dhamija. “Intermittent reactions can be tricky because you don’t know what the patient is exposing themselves to and the allergen could be at work or home.”
- Contact dermatitis can affect up to 6% of the U.S. population.
- The case report Dhamija discussed before the ACAAI involved a patient who visited a hospital emergency room three times during the spring with complaints of a facial rash and eyelid swelling. The patient was sent home with prednisone and was seen one to two weeks later during a telemedicine appointment during which he reported the rash had been going on for two weeks.
- Physicians realized the rash occurred where the elastic parts of his facial mask would rest, explains Kristin Schmidlin, MD, an assistant professor in the UC Division of Immunology, Allergy, and Rheumatology and co-author of the abstract at ACAAI.
- Schmidlin said physicians reduced the amount of prednisone and advised use of topical triamcinolone, a steroid that helps reduce inflammation and is commonly used in treating mouth sores. She said the patient was also advised to use a cotton-based, dye-free mask without elastic.
- The patient was able to find a cloth mask and reported improved symptoms a week later, said Schmidlin.
- The CDC offers some guidelines for making masks at home and that’s a starting point for individuals with contact dermatitis.
- “Instead of using elastics in a facial mask, I would modify it and use cotton-based knot ties around the back of the head to hold the mask in place,” says Dhamija. “We also advise patients to call companies that make facial masks to find out what’s in the product if labeling does not contain enough details.”
- “There are immune reactions to allergens that can be life-threatening but when it comes to contact dermatitis, it doesn’t escalate that far. We can quickly identify the allergen and stop the offending agent. But, some cases can be severe,” said Dhamija. “Treatment usually means avoiding the agent or we can use a topical or oral steroid if needed. It depends on how severe the reaction is and how much of the body is affected. We also take into account how it is impacting the patient’s life or ability to work, for example.”
- “Patch testing is a tool we use to detect contact dermatitis,” said Dhamija. “It’s good to speak with your primary care doctor or ask for a referral to an allergist if you have concerns. Patch testing involves placing a compound we suspect is a problem to your skin. We have you return a few days later and we see if there is a reaction.”
- Dhamija said there is abundant literature documenting patients with contact dermatitis because of allergens such as elastic bands in FFP2 masks, N95 respirators, neoprene rubber masks and medical masks containing formaldehyde or rubber components using carbamates or thiurams.
J. Johns Hopkins COVID-19 Update
November 16, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 54.30 million cases and 1.31 million deaths as of 9am EST on November 16. The WHO reported a new record high for weekly C19 incidence for the ninth consecutive week—3.98 million new cases, a 6.5% increase over the previous week. The WHO also reported a new record high for weekly mortality for the second consecutive week—59,860 deaths, an 11% increase over the previous week.
- 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)
- Montenegro: 994 daily cases per million population (+64; ↑ 3)
- Luxembourg: 927 (+83; ↑ 4)
- Andorra: 904 (-128; ↓ 2)
- San Marino: 884 (+400; new)
- Austria: 809 (+152; ↑ 4)
- Georgia: 793 (+145; new)
- Switzerland: 743 (-205; ↓ 4)
- Liechtenstein**: 738 (-150; ↓ 3)
- Slovenia: 679 (+25; new)
- Poland: 629 (no change; new)
- The Czech Republic fell out of the top 10 in terms of total daily incidence, and it was replaced by Brazil, which jumped all the way to #5. France’s daily incidence decreased by nearly 50% compared to the previous week. Conversely, the daily incidence increased by nearly 40% in the US and 56% in Brazil. The US is reporting more than 3.5 times the incidence as every other country. Armenia, Belgium, the Czech Republic, and France fell out of the top 10 in terms of per capita daily incidence, and they were replaced by Georgia, Poland, San Marino, and Slovenia. San Marino’s C19 incidence increased by 83%, and it jumped all the way to #4.
- The US CDC reported 10.85 million total cases and 244,810 deaths. The US is averaging 148,280 new cases per day, the highest since May 24. The US is averaging 1,180 deaths per day, and it could reach 250,000 cumulative deaths by the end of the week.
- The US reported a new single-day record for daily incidence on Friday, with 194,610 new cases. This is 36% more cases than the previous record, which was reported on the previous day. The US has reported more than 100,000 new cases on 10 of the 11 days since becoming the first country to do so on November 4, including the past 3 days with more than 150,000 new cases. Since that time, the average daily incidence has increased by 65%, and it appears to still be increasing exponentially. Notably, the US reported more than 1 million cases over the past 7 days.
- Two-thirds of all US states have reported more than 150,000 cumulative cases, and 20 have reported more than 200,000 cases:
- On a per capita basis, more than half of all US states are reporting higher cumulative incidence than New York City, the country’s biggest hotspot early in the epidemic, including North and South Dakota, which are reporting more than twice the per capita cumulative incidence as New York City. In terms of mortality, the parts of the country that were affected most severely in the US this spring—e.g., New York City, New Jersey, Massachusetts, Connecticut, and Louisiana—continue to report the highest per capita cumulative mortality; however, over the last 7 days, only Hawai’i, Oregon, and Vermont have reported lower per capita mortality than New York City (0.1 deaths per 100,000 population). On the other end of the spectrum, 4 states have reported 1 or more deaths per 100,000 population—Wyoming (1), Georgia (1), South Dakota (1.6), and North Dakota (1.8)—at least 10 times the current rate in New York City.
- The Johns Hopkins CSSE dashboard reported 11.05 million US cases and 246,255 deaths as of 11:30am EST on November 16.
2. MODERNA VACCINE
- Moderna Therapeutics issued a series of press releases over the past several days regarding the progress for the Phase 3 clinical trials for its candidate SARS-CoV-2 vaccine. Last week, Moderna announced that it identified enough cases among study participants—ie, at least 53—to conduct the first interim analysis on the vaccine’s efficacy.
- The study completed enrollment of 30,000 participants in late October, and the primary metric is preventing symptomatic C19 disease, with secondary aims of preventing severe disease and preventing infection. Last Friday, Moderna announced that Swiss regulatory officials began reviewing the trial’s safety and efficacy data to evaluate the possibility of authorizing its use in Switzerland. The review will occur on a rolling basis, as new data become available, as opposed to waiting until all data are collected, in hopes of accelerating the review process compared to traditional timelines.
- The most noteworthy news, however, was today’s announcement that interim analysis of the data indicates that the candidate vaccine could be nearly 95% effective. Like Pfizer’s announcement last week, this update was provided in a press release, and the actual data still need to be published and reviewed; however, the news is promising that multiple highly efficacious vaccines could be available in 2021. The Moderna interim analysis involved 95 participants with confirmed C19 (90 of which were in the placebo group).
- Notably, 11 severe C19 cases were reported among trial participants, and all were among the placebo group. Among the 95 cases, 15 are aged 65 years or older and 20 are racial or ethnic minorities—12 Hispanic or LatinX, 4 Black or African American, 3 Asian, and 1 multiracial. Moderna estimates the vaccine to be 94.5% efficacious based on the preliminary data, which would be comparable to the Pfizer vaccine. The vaccine also appears to have an acceptable safety profile, with no serious adverse events reported thus far.
- Moderna also announced that the vaccine has demonstrated longer shelf life and greater stability at refrigeration temperatures than initially anticipated. According to the press release, “remains stable at 2° to 8°C (36° to 46°F)…for 30 days” and “at -20° C (-4°F) for up to six months.” The Moderna vaccine could be stored temporarily in standard refrigerators or freezers. Additionally, the Moderna vaccine can remain at room temperature for up to 12 hours and does not require onsite dilution or additional handling at the vaccination site, which could reduce the logistical burden required for mass vaccination.
- Both Pfizer and Moderna are expected to file for Emergency Use Authorization (EUA) with the US FDA, and regulatory authorities in other countries, including the European Medicines Agency, have also announced they will review the Moderna candidate. The news about both vaccine candidates has been received positively and with relief, especially as initial expectations about the efficacy of mRNA vaccines were somewhat low. Neither company has released the full interim analysis or the data analyzed in a journal, however, and the long-term safety and efficacy of these candidates remains to be assessed.
3. HEALTHCARE WORKER BURNOUT
- US C19 incidence is surging to unprecedented levels, nearly reaching 200,000 new cases on November 12. While this surge is commonly described as a “third wave,” the reality, especially for frontline healthcare workers, is that this is just the ever-growing peak of a single, continuous wave since March. The US never successfully contained its “first wave,” so many US healthcare workers never got a reprieve between the second and third surges. The Atlantic published a detailed report on the current state of the US healthcare workforce, as emergency rooms across the country are reaching capacity with C19 patients and medical staff are being pushed to the limit, sometimes working 36-hour shifts.
- The strain is particularly difficult in rural areas in the Midwest and West regions, where hospitals and health systems are running out of bed space and healthcare personnel to care for new patients. The seemingly endless surge in cases across many states has led to concerns of impending and continuing burnout from doctors and nurses, especially as many personnel are required to remain in quarantine or isolation due to their continual contact with C19 patients. In some locations, such as North Dakota, the lack of available doctors and nurses has policies allowing healthcare workers who test positive for SARS-CoV-2 to keep working, as long as they remain asymptomatic.
- The previous 2 surges in the spring and summer provided valuable experience and insight regarding how to best treat C19 patients, and the development and availability of new therapies have helped to an extent. But with holidays rapidly approaching in the US, many are concerned about an impending surge in cases as people may congregate. US healthcare workers, like those in many countries are physically, mentally, and emotionally exhausted, and the third surge is the biggest to date, with no sign of slowing. Increased incidence inevitably brings increased hospitalizations and mortality, but if hospitals and health systems are unable to cope with the surge, including if healthcare workers are too exhausted to operate effectively, the US could risk mortality more like that reported early in the epidemic, when New York City was overwhelmed, except on a national scale.
- As C19 transmission continues to surge in Europe and many countries move to strengthen social distancing restrictions to mitigate transmission risk, Slovakia took a slightly different approach that initially appears to be paying dividends. As we covered previously, Slovakia implemented a plan to test every adult in the country, in addition to enhanced social distancing policies. In the first week of testing, Slovakia tested more than 3.6 million people—approximately two-thirds of the country—and a week later, it retested more than 2 million individuals in high-risk areas. The tests used for this effort are rapid antigen tests, which are slightly less reliable than traditional PCR-based diagnostic tests, but they can provide results in as little as 15-30 minutes. Individuals who tested positive during the nationwide effort were placed in quarantine or isolation to mitigate the risk of further transmission, and contact tracers conducted investigations to identify other at-risk individuals.
- In the weeks since testing began, Slovakia has reported a significant decrease in C19 incidence. Slovakia’s daily C19 incidence fell dramatically from a peak of 2,547 new cases per day on November 4 to 1,610 on November 16, a 33% decrease. Slovakian Prime Minister Igor Matovič attributed the decreased incidence to the testing program and associated quarantine requirements. While Slovakia had a number of other social distancing measures in place—including prohibitions on large gatherings, curfew, and many business closures—some of these measures were tied to testing results to encourage participation. For example, the curfew, in place from 11pm to 5am, required those with exceptions for work, health care, or other essential activities to carry documentation of a negative PCR or antigen test.
- These restrictive social distancing measures have been in place since early October, so it is not easy to distinguish the impact of the testing program, but the downward trend in incidence following the mass testing is certainly promising. Prime Minister Matovič announced that the next round of testing will be conducted the weekend of November 21-22 and will be much more limited in scope than the nationwide effort, focusing cities where the previous round of testing identified SARS-CoV-2 prevalence greater than 1 percent. In the announcement, he noted that continued widespread testing could enable Slovakia to “indulge in a little freedom,” as opposed to facing highly restrictive “lockdown” through the winter months. He suggested that if the testing data continue to provide evidence that the country’s C19 epidemic is moving in the right direction, Slovakia could ease some existing social distancing measures.
- While Slovakia elected to extend its state of emergency for another 45 days, Prime Minister Matovič later announced that Slovakia’s Pandemic Commission approved measures to reopen “cinemas, theaters and churches” at 50% capacity as well as gyms and swimming pools with limited capacity, indicating that the government is confident that the testing program is meeting its aims. While the curfew will remain in place, individuals who are eligible for the noted exceptions will no longer be required to provide documentation of a recent test. As many other countries, particularly in Europe and North America, struggle to combat their respective C19 surges, Slovakia’s experience provides some evidence that widespread testing, in combination with contract tracing and quarantine/isolation, can help contain transmission and enable the relaxation of some social distancing measures.
5. WHITE HOUSE TRANSMISSION
- Last week, multiple news media reports indicated that more than 130 secret service officers, assigned to protect US President Donald Trump and other senior White House officials, have been ordered to quarantine or isolate as a result of testing positive for SARS-CoV-2 or an exposure to a known case, representing approximately 10% of the Secret Service’s core team. Much of that total comes from just the past several weeks, as an outbreak has spread among White House and other administration officials, including President Trump, Chief of Staff Mark Meadows, and Secretary of Housing and Urban Development Ben Carson.
6. PUERTO RICO
- Like many other areas in the US, Puerto Rico is experiencing a surge in C19 incidence that has necessitated the addition of new protective restrictions. The US territory is currently reporting more than 600 cases per day, with projections reaching 1,200 cases per day by mid-December. The Puerto Rican government is taking several approaches to curb the rise in cases. Gyms, churches, restaurants, casinos, and other businesses will be limited to 30% capacity.
- Beaches will also be closed, with the exception of those using them for exercise. Free rapid testing, likely rapid antigen testing, will be available at toll booth locations during the weekends, providing results back in as little as 15 minutes. Mask use will remain mandatory in public spaces. Finally, Governor Wanda Velazquez activated the National Guard to help with the enforcement of an island-wide curfew from 10pm to 5am. These restrictions came into force on November 16 and are currently scheduled to remain in place until December 11. Governor Velazquez cautioned Puerto Ricans to reduce holiday travel and, instead, participate in virtual family get-togethers where possible.