November 25, 2020
Note: CDC tips for making Thanksgiving safer can be found by clicking here.
“The vaccine is going to probably be rolled out by the end of the second week in December.”Dr. Robert Redfield, Director of CDC
“When you take all the data together, everything is consistent with a mutation that increased infectiousness and transmissibility. The virus will continue to change, and while most of those changes will be mere typos, some may be more meaningful There will be the possibility of additional alterations that change the nature of the pandemic.”David Engelthaler, a geneticist at the Translational Genomics Research Institute in Arizona
“It is all too easy for some to take an idea — in this case, for example, personal freedom — and turn it into an ideology.”Pope Francis, criticizing those who refuse to wear a mask
Navigational Tips: Except for the stories listed under Linked Stories, all of the stories listed below are included in this update. And to the extent available, we have embedded links in the title of the stories to the extent available so that you can quickly jump to the original story on the internet if you want by clicking on the title. If you reading the Word document, you can jump to a section by holding down the control key+clicking on the title of the section.]
Highlighted stories includes information we found interesting. (!) indicates a story that includes new, promising/breakthrough or unexpected/surprising information. (*) indicates information that may be useful in connection with your plans and preparations regarding the coronavirus and C19. And © indicates that a story contains information that may contradict or be inconsistent with other information.
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
M. Linked Stories
- Aerodynamics of Infectious Disease: Airflow Studies Reveal Strategies to Reduce Indoor Transmission of C19
- In Response to the Critical Shortage, Researchers Create 3D-Printed Nasal Swab for C19 Testing
- Building a Cell Membrane Defense Against C19
- Folding of SARS-CoV2 Genome Reveals C19 Drug Targets – And Preparation for “SARS-CoV3”
- COVAS Score: New Tool Helps Predict Outcomes for C19
- Female Sex Steroids May Play A Role in Protecting Women
- Bariatric surgery may reduce severity of C19 in patients with obesity
- Face masks slow spread of C19; types of masks, length of use matter
- New therapy for flu may help in fight against C19
- New study provides deep insights into transmission and mutation of the coronavirus
- Study involving seven children’s hospitals shows C19 typically mild in children
- New insight into the effect of hydroxychloroquine undermines its use in C19
- A sulfur molecule to block the coronavirus
- T-cell abnormalities in severe C19 cases
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A. Pandemic Headlines
(In no particular order)
- In the first distribution push, 6.4 million doses of Pfizer’s vaccine will be shipped across the U.S.
- CDC considers shortening recommended 14-day quarantine time for people exposed to Covid-19 to between 7 and 10 days
- Regeneron COVID-19 treatment used by Trump to is being shipped out
- AstraZeneca coronavirus vaccine up to 90% effective
- UK may be days away from approving Pfizer’s coronavirus vaccine
- CDC urges international travelers to be tested 3 times: before, during and after the trip
- Quantas to require COVID-19 vaccine for international flights
- A Revamped Strategic National Stockpile Still Can’t Match The Pandemic’s Latest Surge
- Hospitalizations surge across US
- Heartbreak as COVID cases flood rural hospitals, small-town America
- “We Feel Like We Are Drowning” – Rural Hospitals Overwhelmed By Shortages Of Bed, Staff
- Evidence Builds That an Early Mutation Made the Pandemic Harder to Stop
- Dr. Fauci calls on New York to accept FDA approval of vaccine
- Fauci predicts more than 300,000 COVID-19 deaths by end of year
- Fauci: Middle-aged adults are starting to account for a “substantial” number of COVID-19 hospitalizations
- CDC urges overwhelmed contact tracers to prioritize efforts as cases soar
- ‘We missed the boat in the beginning’: Officials concede contact tracing is no longer effective at containing the virus in the U.S.
- Staten Island emergency field hospital ‘up and running,’ accepts first patient
- Get ready for major backlash to the next wave of lockdowns
- Russian C19 vaccine to cost less than $20, free for citizens
- Putin won’t take Russia’s COVID-19 vaccine
- A Russian vaccine maker reports positive results based on an incomplete trial
- A Chinese firm seeks permission to market a vaccine before announcing it has completed trials
- China Wants Passenger Tracking System for Global Travel Coronavirus Reset
- Quantas to require COVID-19 vaccine for international flights
- Swiss doctors asking patients over 60 to sign Do Not Resuscitate Orders to free up ICU beds
- Head of WHO Suggests COVID Restrictions Will Continue Even After Vaccine
- NC Gov extends mask mandate
- Turkey sees record deaths
- Macron says that France is past the peak of the second wave and that shops can reopen on Saturday
- NYC Mayor De Blasio Unleashes ‘COVID Checkpoints’ To Catch & Fine Travelers Who Violate Holiday Quarantine
- The surge in California shatters records as officials scramble to head it off
- We Must Not Allow Politics To Dictate Science
- Holidays worth COVID-19 risk to one-third of parents
- Despite wide US C19 surge, travelers on the move for Thanksgiving
- Flight map shows staggering amount of flights ahead of Thanksgiving amid C19
- TSA Screens Two Million in Two Days Despite Holiday Travel Warnings
- Most Americans Staying Home For Thanksgiving
- Holiday travel drops, as Americans rethink a comforting ritual
- NYC residents flock to COVID-19 test sites ahead of iffy holiday travel
- You can ignore psuedoscientific rules and celebrate Thanksgiving responsibly
- Britain will loosen most restrictions for a short period to allow people to celebrate Christmas
- Coronavirus is roaring back in parts of Asia, capitalizing on pandemic fatigue
- In Canada’s second lockdown, schools remain open
- Italy’s COVID-19 death toll passes 50,000, with 630 new fatalities
- Britain fails to stop the second wave of COVID-19
- Hong Kong orders all bars and nightclubs to close as infections spike
- Oregon governor urges people to call cops on COVID-19 rule breakers
- COVID-19 hospitalizations in Maine surpass 100 for the first time
- A coalition of African nations launches a clinical trial of treatments for less severe Covid-19 cases
- Young people’s anxiety levels doubled during first C19 lockdown
- Forcing The Sick And Elderly To Die Alone Is Crueler Than COVID-19
- C19 second wave in Myanmar causes dramatic increases in poverty
- Maryland Governor says no one has a constitutional right to walk around with a mask
- Nearly 60% of voters don’t think governors have authority to limit private family gatherings
- US Seafood Industry Flounders Due to C19 – Many Fishmongers May Go Belly Up Without Aid
- NYC to levy 15K fine against Brooklyn synagogue that held illegal wedding
- Pennsylvania governor halts alcohol sales day before Thanksgiving
- COVID-19 school closings leave nation’s rural students isolated
- COVID-19 surge, small gatherings cut into Thanksgiving turkey demand
- Deutsche Bank Mulls Permanent Remote-Work Requirements To Save On Rent
- Internet Searches For “Bidet” Begin To Soar As Toilet Paper Shortage Intensifies
- Man arrested for allegedly spitting at two women hikers, saying ‘I have COVID’
- Grandparents send family cutouts of themselves for holiday gatherings
- Narcissists love being pandemic ‘essential workers’
B. Numbers & Trends (11/24)
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 = 60,088,603
- New Cases (7 day average) = 589,704
- Record high number of new cases (665,604) occurred on 11/20
- 2nd highest 7 day average of new cases (slightly lower than yesterday)
- During the last 30 days, 7 day average has increased from 446,725 to 589,704, an increase of 32% (or an annualized rate of 384%)
- Since 11/13:
- the rate of increase in 7 day average has slowed significantly
- 7 day average has increased from 584,546 to 589,704, an increase of 0.8% (or an annualized rate of 24%)
US Cases & Testing:
- Total Cases = 12,955,145
- New Cases (7 day average) = 178,692
- Percentage of New Global Cases (7 day average) = 30.3%
- Total Number of Tests = 184,361,379
- Percentage of positive tests (7 day average) = 11.5%
- Record high number of new cases (204,163) occurred on 11/20
- Record high 7 day average of new cases
- During the last 30 days:
- 7 day average has increased at a rapid rate
- 7 day average has increased from 70,269 to 178,692, an increase of 154.3% (an annualized increase of 1,851.6%) (!)
- The growth rate in the 7 day average appears to be slowing down, but it is too early to tell if that is trend, particularly in light of the holiday season
- 7 day average of positive test rate has declined from 12.2% to 11.5% during the last week, a decrease of 6%
- Total Deaths = 1,413,800
- New Deaths (7 day average) = 10,044
- Record high number of new deaths (11,720) occurred on 11/24
- Record high 7 day average of new deaths
- During the last 30 days:
- 7 day average of new deaths has been increasing at a rapid rate
- 7 day average has increased from 5,946 to 10,044, an increase of 68.9% (or an annualized rate of 826.8%)
- Total Deaths = 265,898
- New Deaths (7 day average) = 1,657
- Percentage of Global New Deaths (7 day average) = 16.5%
- During the last 30 days:
- 7 day average of new deaths has been increasing at a rapid rate
- 7 day average has increased from 824 to 1,657, an increase of 101.1% (an annualized increase of 1,213.2%) (!)
- US Percentage of Global New Deaths is almost 50% less than the percentage of Global New Cases, which means that US survival rate is much higher than the rest of the world and/or other countries are significantly undercounting their cases
3. Top 5 States in Cases, Deaths, Hospitalizations, ICU Patients, & Positivity (11/24)
- After peaking at a positivity rate of 12.3% on 11/18, the US positivity rate has seen a daily decrease to 11.5%.
- ND still leads the nation at 61.8%, unchanged since 11/17. MO positivity has surged to 59.5% from 39.5% one week ago. SD (43.7%) and IA (40.3%) positivity rates have both decreased from one week ago (both were +50%)
- Overall, 27 states reported lower positivity rates over the last seven days. Similar to what we saw in the Sunbelt states during the summer surge, falling positivity rates may be an early indicator that the cases are peaking.
- Two states (IA, SD) 7-day positivity rates greater than 40%.
- Six states (KS, ID, NE, NV, WI, IN) 7-day positivity rates greater than 30%.
- Ten states (UT, MN, PA, RI, NM, NH, CO, AL, MT, AZ) had 7-day positivity rates greater than 20%.
- In total, 45 states have 7-day positivity rates greater than 5% (+unchanged since 11/17)
- Hospitalizations in the US have increased to 88,080, up 14.5% since 11/17. While hospitalizations are still increasing, the weekly percentage increase has fallen from 20.3% on 11/19.
- 31 states have had increases of hospitalized patients of more than 10% since 11/17. On 11/19, 39 states had +10% gains
- 27 states have more than 1,000 hospitalized patients (+2 since 11/17)
- Five states saw decreases in the number of hospitalized patients (HI, WI, IA, ND, SD).
- ICU Patients in the US have increased to 17,127 up from 14,851 (+ 15.3%) since 11/12. ICU patients have increased, but the weekly percentage increase has fallen from 21.7% on 11/19
- 26 states have seen the number of ICU patients increase by more than 10% since 11/12 (-2 since 11/17)
- 30 states have more than 100 patients in ICU, (+1 states since 11/17)
- Five states (ND, DE, SC, IA, WI) saw decreases in the number of ICU patients since 11/17
4. U.S. Hospitalizations Pass 85,000
What to Know
- U.S. hospitalizations surpassed 85,000, setting a record for the 14th straight day.
- C19 has become less deadly.
- The U.S. government is aiming to distribute 40 million vaccine doses by year’s end.
- C19 cases hitting new highs on the West Coast.
- The U.S. recorded 169,190 new coronavirus cases on Monday, and the number of patients hospitalized reached a new high for the 14th straight day.
- The cumulative case count now exceeds 12.4 million, according to data compiled by Johns Hopkins University. There were a further 889 C19 deaths Monday, bringing the total to 257,701.
- Hospitalized patients as of Monday totaled 85,836, according to the Covid Tracking Project. The U.S. has set a record every day since hospitalizations first passed 60,000 on Nov. 10, according to the project’s data.
- With the pandemic raging through much of the U.S. and Europe, the World Health Organization’s C19 technical lead Maria Van Kerkhove said Monday that families deciding whether to gather over the holiday season had to weigh up personal circumstances and risks—but that there was no way to cut the risk to zero.
- “Many people have access to ability to connect virtually, and I think that may be the way that many areas need to go,” she said.
- Governments crafting policies must balance epidemiological risk against economic and social cost, said Michael Ryan, who heads the WHO’s health-emergencies program, adding that transmission increased in Canada when it celebrated Thanksgiving last month.
- The U.S. seven-day moving average of new cases, which smooths out the numbers, climbed to 172,118 as of Monday, according to a Wall Street Journal analysis of Johns Hopkins data. That is higher than the 14-day moving average of 163,225, a sign cases are on the rise.
- The seven-day average for deaths has also exceeded the 14-day average since Oct. 19, but they are lower than in the first months of the pandemic, as doctors understand better how to treat the disease.
C. New Scientific Findings & Research
1. Frequent, Rapid Testing Could Cripple C19 Within Weeks
- Testing half the population weekly with inexpensive, rapid-turnaround C19 tests would drive the virus toward elimination within weeks—even if those tests are significantly less sensitive than gold-standard clinical tests, according to a new study published today by CU Boulder and Harvard University researchers.
- Such a strategy could lead to “personalized stay-at-home orders” without shutting down restaurants, bars, retail stores and schools, the authors said.
- “Our big picture finding is that, when it comes to public health, it’s better to have a less sensitive test with results today than a more sensitive one with results tomorrow,” said lead author Daniel Larremore, an assistant professor of computer science at CU Boulder. “Rather than telling everyone to stay home so you can be sure that one person who is sick doesn’t spread it, we could give only the contagious people stay-at-home orders so everyone else can go about their lives.”
- For the study, published in the journal Science Advances, Larremore teamed up with collaborators at CU’s BioFrontiers Institute and the Harvard T.H. Chan School of Public Health to explore whether test sensitivity, frequency, or turnaround time is most important to curb the spread of C19.
- The researchers scoured available literature on how viral load climbs and falls inside the body during an infection, when people tend to experience symptoms, and when they become contagious.
- They then used mathematical modeling to forecast the impact of screening with different kinds of tests on three hypothetical scenarios: in 10,000 individuals; in a university-type setting of 20,000 people; and in a city of 8.4 million.
- When it came to curbing spread, they found that frequency and turnaround time are much more important than test sensitivity.
Curbing infectiousness by 80%
- For instance, in one scenario in a large city, widespread twice-weekly testing with a rapid but less sensitive test reduced the degree of infectiousness, or R0 (“R naught”), of the virus by 80%. But twice-weekly testing with a more sensitive PCR (polymerase chain reaction) test, which takes up to 48 hours to return results, reduced infectiousness by only 58%. In other scenarios, when the amount of testing was the same, the rapid test always reduced infectiousness better than the slower, more sensitive PCR test.
- That’s because about two-thirds of infected people have no symptoms and as they await their results, they continue to spread the virus.
- “This paper is one of the first to show we should worry less about test sensitivity and, when it comes to public health, prioritize frequency and turnaround,” said senior co-author Roy Parker, director of the BioFrontiers Institute and a Howard Hughes Medical Institute investigator.
- The study also demonstrates the power of frequent testing in shortening the pandemic and saving lives.
- In one scenario, in which 4% of individuals in a city were already infected, rapid testing three out of four people every three days reduced the number ultimately infected by 88% and was “sufficient to drive the epidemic toward extinction within six weeks.”
- The study comes as companies and academic research centers are developing low-cost, rapid turnaround tests that could be deployed in large public settings or commercialized for do-it-yourself use.
- Sensitivity levels vary widely. Antigen tests require a relatively high viral load – about 1,000 times as much virus compared to the PCR test — to detect an infection. Another test, known as RT-lamp (reverse transcription loop-mediated isothermal amplification), can detect the virus at around 100 times as much virus compared to the PCR. The benchmark PCR test typically provided by medical professionals requires as little as 5,000 to 10,000 viral RNA copies per milliliter of sample, meaning it can catch the virus very early or very late.
- In the past, federal regulators and the public have been reluctant to embrace rapid tests out of concern that they may miss cases early in infection. But, in reality, an infected person can go from 5,000 particles to 1 million viral RNA copies in 18 to 24 hours, said Parker.
- “There is a very short window, early in infection, in which the PCR will detect the virus but something like an antigen or LAMP test won’t,” Parker said.
- And during that time, the person often isn’t contagious, he said. The authors recently used these findings to call for a shift in the way we think about test sensitivity in The New England Journal of Medicine.
- “These rapid tests are contagiousness tests,” said senior co-author Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. “They are extremely effective in detecting C19 when people are contagious.”
- They are also affordable, he added. The rapid tests can cost as little as $1 each and return results in 15 minutes. Some PCR tests can take several days.
Cheap, DIY tests for every household
- Mina envisions a day when the government sends simple, cheap DIY tests to every home in the United States. Even if half of Americans tested themselves weekly and self-isolated if positive, the result would be profound, he said.
- “Within a few weeks we could see this outbreak going from huge numbers of cases to very manageable levels,” Mina said.
- Rapid testing could also be the key to breathing life back into former superspreader threats like football stadiums, concert venues and airports, with patrons testing themselves on the way in and still wearing masks as a precautionary measure, Larremore said.
- “Less than .1% of the current cost of this virus would enable frequent testing for the whole of the U.S. population for a year,” said Mina, referencing a recent economic analysis published by the National Bureau of Economic Research.
- The authors say they are heartened to see that several countries have already begun testing all of their citizens, and hopeful that the new U.S. administration has named rapid testing as a priority. Last week, the FDA approved the first at-home rapid test.
- “It’s time to shift the mentality around testing from thinking of a COVID test as something you get when you think you are sick to thinking of it as a vital tool to break transmission chains and keep the economy open,” Larremore said.
2. Understanding dangerous droplet dynamics: Socially Distancing Futile Once Indoors
- Researchers who study the physics of fluids are learning why certain situations increase the risk that droplets will transmit diseases like C19.
- At the 73rd Annual Meeting of the American Physical Society’s Division of Fluid Dynamics, the scientists offered new evidence showing why it’s dangerous to meet indoors–especially if it’s cold and humid, and even if you’re more than six feet away from other people. They suggested which masks will catch the most infectious droplets. And they provided new tools for measuring super-spreaders.
- “Present epidemiological models for infectious respiratory diseases do not account for the underlying flow physics of disease transmission,” said University of Toronto engineering professor Swetaprovo Chaudhuri, one of the researchers.
- But fluids and their dynamics are critical for shaping pathogen transport, which affects infectious disease transmission, explained mathematical physicist and professor Lydia Bourouiba, Director of The Fluid Dynamics of Disease Transmission Laboratory at MIT. She gave an invited talk on the body of work she has produced over the last ten years elucidating the fluid dynamics of infectious diseases and disease transmission.
- “My work has shown that exhalations are not isolated droplets but in fact come out as a turbulent, multiphase cloud. This gas cloud is critical in enhancing the range and changing the evaporation physics of the droplets within it,” said Bourouiba. “In the context of respiratory infectious diseases, particularly now C19, this work underscores the importance of changing distancing and protection guidelines based on fluid dynamics research, particularly regarding the presence of this cloud.”
- Bourouiba presented examples from a range of infectious diseases including C19 and discussed the discovery that exhalation involves different flow regimes, in addition to rich unsteady fluid fragmentation of complex mucosalivary fluid. Her research reveals the importance of the gas phase, which can completely change the physical picture of exhalation and droplets.
- Nordic Institute for Theoretical Physics scientist Dhrubaditya Mitra and his team realized they could use the mathematical equations that govern perfume to calculate how long it would take for viral droplets to reach you indoors. It turns out: not very long at all.
- Perfume worn by someone at the next table or cubicle reaches your nose thanks to turbulence in the air. Fine droplets spewed by an infected person spread in the same way. The researchers found that below a relative distance known as the integral scale, droplets move ballistically and very fast.
- Even above the integral scale, there is danger. Consider an example where the integral scale is two meters. If you were standing three meters–just under ten feet–from an infected person, their droplets would almost certainly reach you in about a minute.
- “It showed us how futile most social distancing rules are once we are indoors,” said Mitra, who conducted the research with colleague Akshay Bhatnagar at the Nordic Institute for Theoretical Physics and Akhilesh Kumar Verma and Rahul Pandit at the Indian Institute of Science.
- Besides traveling further and faster, droplets may also survive longer indoors than previously believed.
- Research in the 1930s analyzed how long respiratory droplets survive before evaporating or hitting the ground. The nearly century-old findings form the basis of our current mantra to “stay six feet away” from others.
- Physicists from the University of Twente revisited the issue. They conducted a numerical simulation indicating that droplet lifetimes can extend more than 100 times longer than 1930s standards would suggest.
- “Current social distancing rules are based on a model which by now should be outdated,” said physicist Detlef Lohse, who led the team.
- In a cold and humid space, exhaled droplets don’t evaporate as quickly. The hot moist puff produced also protects droplets and extends their lifetimes, as do collective effects.
- Some droplets are more likely than others to make you sick. University of Toronto’s Chaudhuri, with researchers from the Indian Institute of Science and the University of California San Diego, investigated why, using human saliva droplet experiments and computational analyses.
- They found that some of the most infectious droplets start out at 10 to 50 microns in size. “With certain assumptions, it appears that if everyone wears a mask that can prevent ejection of all droplets above 5 microns, the pandemic curve could be flattened,” said Chaudhuri.
- Dried droplet residue also poses a serious risk: It persists much longer than droplets themselves and can infect large numbers of people if the virus remains potent.
- The team used their findings to develop a disease transmission model. “Our work connects the microscale droplet physics and its fundamental role in determining the infection spread at a macroscale,” said Chaudhuri.
- To better understand droplet dynamics in the C19 pandemic, a team from Northwestern University and the University of Illinois at Urbana-Champaign tested the capacities of a new wearable device. The thin, wireless, flexible sensor attaches like a sticker to the bottom of the neck to capture vital signals. Ongoing clinical studies are using the device with hospital patients.
- The team found that the device distinguishes between coughing, talking, laughing, and other breathing activities with its machine learning algorithms. Researchers used particle tracking velocimetry and a decibel meter to analyze droplets produced by device wearers.
- “Different types of speech can generate drastically different numbers and dynamics of droplets,” said biomedical engineering researcher Jin-Tae Kim, who led the investigation.
- The device can help shed light on why some individuals become unusually infectious–the so-called super-spreaders. “Our findings further address the critical need for continuous skin-integrated sensors to better comprehend the pandemic,” said Kim.
3. EBSELEN: A Mechanism to Stop C19 Replication
- Stopping the replication of SARS-CoV-2 is likely possible thanks to a compound called EBSELEN: a group of researchers from the Politecnico di Milano has communicated aspects relevant to the blocking of replication mechanism in the New Journal of Chemistry.
- Two important aspects of the propagation of a virus are its ability to enter the host’s cells, that is, to infect the host, and then to replicate in infected cells.
- As for SARS-CoV-2, the Mpro protein plays an important role in the replication and transcription of the virus. Mpro therefore represents a particularly promising target for blocking the virus itself because a compound that inhibits Mpro blocks the virus.
- EBSELEN proved to be the most potent inhibitor of Mpro in a study examining approximately 10,000 selected compounds. In their study, the researchers at Politecnico elucidate key aspects of the Mpro blocking mechanism by EBSELEN.
- “We have identified that the selenium atom of EBSELEN strongly interacts with some groups typically present in proteins via the chalcogen bond, a weak bonding that has been studied for years in our laboratories; this binding may contribute to the inhibition of the virus replication. This represents an important step forward in the fight against C19. ” Says Prof. Giuseppe Resnati of the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” of the Politecnico di Milano.
4. Chicago study shows C19 cases 16 times higher than currently predicted
- A large amount of evidence has accumulated that the reported cases of C19 is significantly lower than the reality. A startling new case study of Chicago, led by a team of researchers at Northwestern University in Illinois, USA, suggests a 16-fold higher incidence of the coronavirus (SARS-CoV-2) infection than previously thought. This is judging from seroprevalence (antibody presence blood testing) figures, rather than the number of RT-PCR-positives reported there (via swab sample testing of symptomatic patients).
- The study underscores the importance of using a convenient and sensitive self-collected sampling method that can offer a quantitative assessment of the antibody titers in the community, even with low titers.
- Serologic testing for antibodies is important in many ways in the current C19 pandemic. Not only does it help us assess the scale of a population’s exposure to the pathogen, but it may also allow us to gauge levels of immunity through understanding the prevalence and titers of antibodies in the community. However, the testing method and the viral antigen against which antibodies are raised may vary, and with them, the seropositivity estimates.
- The team reported their findings on the preprint server medRxiv* in November 2020.
Dried blood spot serology
- Currently, the majority of antibody tests are based on blood or serum testing. This, however, depends on the availability of a healthcare center and a skilled worker to administer them. Such studies are thus likely to be biased from the beginning. Another option is using point-of-care assays based on lateral flow devices, but these are neither as sensitive or as specific as laboratory assays.
- The current Screening for Coronavirus Antibodies in Neighborhood (SCAN) study assessed seroprevalence as measured from dried blood spots (DBS) from a fingerprick. This method had been validated earlier for the qualitative measurement of anti-RBD IgGs using ELISA.
- The researchers used a dried blood spot (DBS) assay to quantitatively measure the presence of anti-spike receptor-binding domain (RBD) antibodies against SARS-CoV-2 in over 1,500 individuals. The participants were enrolled by online advertisements (813) or from a medical school (730 staff, faculty and non-treating staff).
- The latter group included both essential workers (those working outside of the home) and non-essential workers (those working from home) during the initial lockdown of early 2020. The blood spots were on a card format, and could be either mailed back or dropped off at the testing center in person.
- The researchers found that about one in five of the tested samples showed anti-RBD IgG antibodies. The seropositivity was about 23% among those aged 18-29 years and 40-49 years, around 18-19% in those aged 30-39 years and 50-59 years. However, it was lowest, at around 13%, among those over the age of 60.
- The proportion of detection was similar among samples sent in by mail or returned in person. The seroprevalence was also similar among essential and non-essential workers and among males and females.
- The testing began after a partial relaxation of the stay-at-home orders, from late June 2020 through the first week of September 2020. The importance of the comparable seropositivity estimate among essential versus non-essential workers could be because of the late timing of the survey, when some shelter-in-place orders had already been relaxed.
Quantitative measure of IgG directed to the receptor binding domain of SARSCoV-2 spike glycoprotein. Samples were acquired through the Screening for Coronavirus Antibodies in Neighborhood (SCAN) between June 24, 2020 and September 6, 2020 (n= 1545). A) Overlap between the IgG range seen in the community-acquired SCAN seropositive samples (light purple) and non-hospitalized C19+ seropositive samples (dark purple, far right). B) 19.8% (306 of 1545) of SCAN samples were seropositive with a median IgG concentration of 0.62 µg/ml SCAN for the seropositive group. The median concentration of the seronegative SCAN group was 0.11 µg/ml. As a comparator, shown is the range of IgG detected from 96 non-hospitalized and 22 ICU hospitalized individuals with C19 documented by a positive nucleic acid test for SARS-CoV-2 virus. The median IgG concentration was 5.2 µg/ml for the non-hospitalized C19+ group and 98.5 µg/ml for the ICU hospitalized C19+ group. The SARS-CoV-2 RBD IgG ELISA seropositive threshold is marked by the red line at 0.39µg/ml. Two hundred and forty-four seronegative samples with an IgG concentration below 0.001 were plotted at 0.001. Comparing seropositive groups * p<0.0001 by Wilcoxon-Mann-Whitney Test. Both seronegative groups are significantly different than all seropositive groups.
IgG titers comparable in mild and asymptomatic cases
- The researchers also observed similar IgG titers among those who were seropositive in the study, and those who were identified by self-detection but not hospitalized. This could indicate that the degree of immune stimulation and immune response was similar among these groups.
- However, the median titer among those admitted to an intensive care unit was 12 times higher than the latter group (98.5 μg/ml versus 5.2 μg/ml).
- On the other hand, only 19 participants (1.2%) reported that they had been tested positive for C19 before this date. Of these, 18 were also anti-RBD IgG positive.
Anti-RBD antibodies more useful than anti-nucleocapsid antibodies
- The researchers cross-checked 28 samples from patients who had recovered after symptomatic C19, all of whom had a positive viral test, against 92 samples from symptomatic individuals who did not have such a result. They found both groups showed a low level of agreement between antibodies to these two antigens, nucleocapsid (N) and RBD
- About a fifth of the 28 symptomatic C19 positives had only anti-RBD IgG without anti-N antibodies. Conversely, around 75% were positive for both antibodies. Only one participant was negative for both antibodies.
- Of the 92 SCAN samples, over 70% had anti-RBD IgG, among which 45/65 had only anti-RBD IgG, while 20/65 samples had both antibodies, and none had both negative. The implication is that antibodies targeting the RBD are probably more useful in detecting the seroprevalence.
- Most of the participants who had an initial seropositive test continued to show detectable median concentrations of IgG from day 0 to 73-166 days later, that is, for about 4 months. In one case, the anti-RBD IgG titer was stable for 3 months and then spiked. This patient had a history of suggestive symptoms two days before, but the PCR test was negative. However, the test was done 25 days after the earliest symptom, which may account for the negative result. Or, the viral load may never have crossed the limit of detection of the test. However, the researchers attribute this result to possible re-exposure to the virus.
What are the implications?
- The researchers detected a high prevalence of anti-RBD antibodies, but it is not clear if they are protective or neutralizing. Further studies will be required to clarify if seropositives are less susceptible to infection than seronegatives.
- About 75% of the community showed persistent seropositivity, with at least one showing some evidence of re-exposure. With respect to the longitudinal pattern of anti-RBD IgG, the researchers say: “We hypothesize this pattern reflects re-exposure to SARS-CoV-2. Whether this pattern portends what might occur with re-exposure generally, or even after vaccines become available, remains for future researchers to explore.”
D. Vaccines & Testing
1. Moderna’s C19 vaccine not proven to stop spread of virus
- Moderna’s coronavirus vaccine may not get life back to normal right away because it hasn’t yet been proven to prevent the deadly bug from spreading, the company’s top doctor says.
- Research has shown that the biotech firm’s shot is effective at preventing people from getting sick with C19, but there’s no hard evidence that it stops them from carrying the virus “transiently” and potentially infecting others who haven’t been vaccinated, according to Dr. Tal Zaks, Moderna’s chief medical officer.
- “I think we need to be careful, as we get vaccinated, not to over-interpret the results,” Zaks told Axios in a TV interview released Monday. “When we start the deployment of this vaccine, we will not have sufficient concrete data to prove that this vaccine reduces transmission.”
- “Do I believe that it reduces transmission? Absolutely yes, and I say this because of the science,” he added. “But absent proof, I think it’s important that we don’t change behaviors solely on the basis of vaccination.”
- Zaks’ comments offer another sign that it will take time for a vaccine to bring an end to the global pandemic and help the economy recover even though drugmakers are working at a breakneck pace to produce a safe and effective inoculation.
- Massachusetts-based Moderna revealed last week that its experimental vaccine was nearly 95% effective in a late-stage clinical trial. Pfizer and AstraZeneca have also reported that their shots are highly effective at warding off C19.
- Pfizer asked the US Food and Drug Administration to clear its vaccine for emergency use on Friday, and Moderna is expected to submit a similar request in the coming weeks. But all three companies will have to navigate the logistical challenge of distributing the vaccines around the world once regulators approve the shots.
- While US officials say they plan to have millions of doses ready by the end of the year, a vaccine is not expected to be widely distributed until next spring.
2. Oxford’s C19 vaccine results are puzzling scientists
- A highly anticipated C19 vaccine has delivered some encouraging — but head-scratching — results. The vaccine developed by the University of Oxford, UK, and pharmaceutical giant AstraZeneca was found to be, on average, 70% effective in a preliminary analysis of phase III trial data, the developers announced in a press release on 23 November.
- But the analysis found a striking difference in efficacy, depending on the amount of vaccine delivered to a participant. A regimen consisting of two full doses given a month apart looked to be just 62% effective. But, surprisingly, participants who received a lower amount of the vaccine in a first dose and then the full amount in the second dose were 90% less likely to develop COVID, compared with participants in the placebo arm.
- Last week, Pfizer and BioNTech reported that their RNA-based vaccine was around 90% effective after the trial reached its primary endpoint, and an interim analysis of Moderna’s RNA vaccine showed it worked roughly as well.
- Researchers caution against making head-to-head comparisons of vaccines based on incomplete data. The disparity in the latest results mean there is considerable uncertainty in precisely how well the Oxford vaccine protects against C19 without more data from ongoing efficacy trials, say scientists. “We’re slightly in danger of rushing to compare apples and oranges,” says Daniel Altmann, an immunologist at Imperial College London. “There’s a long, long way to go before these data settle down and get reported and published in full.”
- The Oxford–AstraZeneca vaccine is made from a cold-causing ‘adenovirus’ that was isolated from the stool of chimpanzees and modified so that it no longer replicates in cells. When injected, the vaccine instructs human cells to produce the SARS-CoV-2 spike protein — the immune system’s main target against coronaviruses.The vaccine entered phase III efficacy trials before other frontrunners, including Pfizer and Moderna, and trials are ongoing in countries including the United States, South Africa, Japan and Russia. The 23 November analysis is based on 131 C19 cases among more than 11,000 trial participants in the United Kingdom and Brazil, up to 4 November.
- Overall, the developers found that the two-dose vaccine had an efficacy of 70%, when measured two weeks after participants received their second dose. But that figure is an average of the 62% and 90% efficacy figures from the two different dosing regimens. “90% is pretty good, but the 62% for the second tested regimen are not that impressive,” Florian Krammer, a virologist at a virologist at Icahn School of Medicine at Mount Sinai in New York City said on Twitter.
- A top priority for researchers is understanding why the vaccine seems to have performed so much better with a lower first dose. One explanation could lie in the data: the trial might not have been big enough to gauge the difference between the two regimens, and the differences will vanish once more cases of C19 are detected, says Luk Vandenberghe, a virologist at the Massachusetts Eye and Ear Institute and Harvard Medical School in Boston. The more effective ‘half-dose, full dose’ results were based on 2,741 trial participants, whereas the less efficacious arm included 8,895 volunteers. The press release did not specify in which group cases occurred.
- Stephen Evans, a statistical epidemiologist at the London School of Hygiene and Tropical Medicine, estimates, based on the data, the group that the ‘half-dose, full dose’ regimen could have an efficacy as low as 66%.
- But, if the differences are bona fide, researchers are eager to understand why. “I don’t think it’s an anomaly,” says Katie Ewer, an immunologist at Oxford’s Jenner Institute who is working on the vaccine. “I’m keen to get into the lab and start thinking about how we address that question.” She has two leading theories for why a lower first dose might have led to better protection against COVID. It’s possible that lower doses of vaccine do a better job at stimulating the subset of immune cells called T cells that support the production of antibodies, she says.
- Another potential explanation is the immune system’s response against the chimpanzee virus. The vaccine triggers an immune response not only to the SARS-CoV-2 spike protein, but also to components of the viral vector. It’s possible that the full first dose blunted this reaction, says Ewer. She plans to look at antibody responses against the chimpanzee virus to help address this question.
- “This is a plausible explanation,” says James Wilson, a virologist at the University of Pennsylvania in Philadelphia who pioneered the use of adenoviruses for vaccines in the 1990s. By giving a half-dose first, “it is possible that AstraZeneca threaded the needle with their dosing,” he adds.
- Hildegund Ertl, a viral immunologist at the Wistar Institute in Philadelphia, says results make sense in the light of some of her work on adenovirus vaccines in mice. She, too, has found that a low first dose can lead to better protection than a higher first dose in a two-dose vaccine. She thinks this is because a lower first dose leads more quickly to the establishment of ‘memory’ immune cells that are triggered by a second-dose boost. Waiting longer between the two doses could achieve the same effect.
- Meanwhile, AstraZeneca hopes to gather more data on the dosing regimen. The company has so far given the vaccine to around 10,000 participants in a US arm of the efficacy trial, which was paused for more than a month in the summer while a neurological condition in a trial participant was investigated.
- The company plans to ask regulators whether it can modify the trial to include the more efficacious dosing regimen, Mene Pangalos, AstraZeneca’s vice-president of biopharmaceuticals research, said at a press briefing.
- “It would be madness to use more vaccine than you needed to get less efficacy,” says Ewer. “I think we will see a move towards rollout of the ‘low dose, standard dose’ regime.”
Hints of optimism
- While Oxford and AstraZeneca make sense of their trial data and gather more, there is reason for optimism in other facets of the vaccine’s performance, say scientists. No participants who received the vaccine were hospitalized or developed severe COVID, suggesting the vaccine may do a good job preventing such infections.
- There were also hints that the vaccine may prevent people from transmitting the virus, even if they aren’t showing symptoms. In the trial’s UK arm, some participants routinely swabbed themselves for SARS-CoV-2 testing, even if they weren’t showing symptoms. Differences in infection rates between people who received the placebo and the Oxford vaccine suggest the vaccine blocks transmission, says Ewer. (Pfizer and Moderna’s trials tested only people who showed symptoms.)
- Even with a question mark hanging over its efficacy, the Oxford–AstraZeneca vaccine may see wider rollout than some other COVID immunizations. The vaccine is stable at refrigerator temperatures, in contrast to Pfizer and BioNtech’s vaccine which must be stored at –70 ºC until hours before vaccination.
- And more of the vaccine may be available sooner, relative to other jabs. AstraZeneca estimates that it will have 200 million doses ready worldwide by the end of 2020 and capacity to produce 100 million to 200 million doses per month once production is ramped up, according to Pam Cheng, vice-president for operations and information technology at AstraZeneca.
- “The battle really between all these vaccines is going to be really a logistical one,” says Vandenberghe. “We will be able to use every dose that becomes available.”
E. Improved & Potential Treatments
1. Century-Old Vaccine May Be Useful Against C19 Coronavirus
- A widely used tuberculosis vaccine is associated with reduced likelihood of contracting C19, according to a new study by Cedars-Sinai. The findings raise the possibility that a vaccine already approved by the FDA may help prevent coronavirus infections or reduce severity of the disease.
- The vaccine, known as Bacillus Calmette-Guérin (BCG), was developed between1908 and 1921 and is administered to more than 100 million children around the world every year. In the U.S., it is FDA-approved as a drug to treat bladder cancer and as a vaccine for people at high risk of contracting TB. The BCG vaccine is currently being tested in multiple clinical trials worldwide for effectiveness against C19.
- In the new study, published online on November 19, 2020, in The Journal of Clinical Investigation, investigators tested the blood of more than 6,000 healthcare workers in the Cedars-Sinai Health System for evidence of antibodies to SARS-CoV-2, the virus that causes C19, and also asked them about their medical and vaccination histories.
- They found that workers who had received BCG vaccinations in the past-nearly 30% of those studied-were significantly less likely to test positive for SARS-CoV-2 antibodies in their blood or to report having had infections with coronavirus or coronavirus-associated symptoms over the prior six months than those who had not received BCG. These effects were not related to whether workers had received meningococcal, pneumococcal or influenza vaccinations.
- The reasons for the lower SARS-CoV-2 antibody levels in the BCG group were not clear, according to Moshe Arditi, MD, director of the Pediatric and Infectious Diseases and Immunology Division at Cedars-Sinai and co-senior author of the study.
- “It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus,” said Arditi, professor of Pediatrics and Biomedical Sciences. “We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections.”
- In the new study, the lower antibody levels in the BCG group persisted despite the fact that these individuals had higher frequencies of hypertension, diabetes, cardiovascular diseases and COPD, which are known risk factors for being more susceptible to SARS-CoV-2 and developing the more severe forms of C19 illness.
- While noting that no one believes BCG will be more effective than a specific vaccine for C19, Arditi explained that it could be more quickly approved and made available, given that it has a strong safety profile demonstrated by many years of use. “It is a potentially important bridge that could offer some benefit until we have the most effective and safe COVID19 vaccines made widely available,” he said.
- “Given our findings, we believe that large, randomized clinical trials are urgently needed to confirm whether BCG vaccination can induce a protective effect against SARS-CoV2 infection,” said Susan Cheng, MD, MPH, MMSc, associate professor of Cardiology and director of Public Health Research at the Smidt Heart Institute at Cedars-Sinai. She was the other co-senior author of the study. The first author was Magali Noval Rivas, PhD, assistant professor of Pediatrics at Cedars-Sinai.
- In fact, a number of randomized clinical trials have been launched to study the potential protective effects of BCG vaccination against C19. Along with Texas A&M University, Baylor College of Medicine, and the University of Texas MD Anderson Cancer Center, Cedars Sinai is a site for the U.S. arm of this ongoing trial, which is recruiting hundreds of healthcare workers. Arditi serves as the principal investigator of this clinical trial at Cedars-Sinai.
- “It would it be wonderful if one of the oldest vaccines that we have could help defeat the world’s newest pandemic,” Arditi said.
2. The drug aprotinin inhibits entry of the coronavirus in host cells
- The surface of the coronavirus (SARS-CoV-2) is studded with spike proteins. The virus needs these in order to dock onto proteins (ACE2 receptors) on the surface of the host cell. Before this docking is possible, parts of the spike protein have to be cleaved by the host cell’s enzymes – proteases.
- In cell culture experiments with various cell types, the international scientific team led by Professor Jindrich Cinatl, Institute for Medical Virology at the University Hospital Frankfurt, Professor Martin Michaelis, and Dr Mark Wass (both University of Kent) demonstrated that the protease inhibitor aprotinin can inhibit virus replication by preventing SARS-CoV2 entry into host cells. Moreover, aprotinin appears to compensate for a SARS-CoV2-induced reduction of endogenous protease inhibitors in virus-infected cells.
- Influenza viruses require host cell proteases for cell entry in a similar way as coronaviruses. Hence, an aprotinin aerosol is already approved in Russia for the treatment of influenza.
- Professor Jindrich Cinatl said: “Our findings show that aprotinin is effective against SARS-CoV2 in concentrations that can be achieved in patients. In aprotinin we have a drug candidate for the treatment of C19 that is already approved for other indications and could readily be tested in patients.”
F. Concerns & Unknowns
1. Diabetic eye disease associated with five-fold risk of severe C19
- People with diabetes and eye disease have a five-fold increased risk of requiring intubation when hospitalized with C19.
- The study, published today in Diabetes Research and Clinical Practice by King’s College London, identified for the first time the risk associated with diabetic retinopathy and C19.
- Diabetic eye disease is a common complication of diabetes and is caused by damage to the small blood vessels in the eye. In 2014, the prevalence of diabetic retinopathy was 54.6% in people with Type 1 diabetes and 30.0% in people with Type 2 diabetes*.
- The study investigated 187 people with diabetes (179 with type 2 diabetes and 8 with type 1 diabetes) hospitalised with C19 at Guy’s and St Thomas’ NHS Foundation Trust between 12th of March and 7th of April 2020.
- Diabetic retinopathy was reported in 67 (36%) of patients, the majority with background retinopathy. Of the 187 patients hospitalised with severe C19, 26% were intubated and 45% of these patients had retinopathy. Retinopathy was associated with a five-fold increased risk for intubation. In the cohort, 32% of patients died and no association was observed between retinopathy and mortality.
- First author of the study, Dr Antonella Corcillo from the School of Cardiovascular Medicine and Sciences at King’s College London said: “This is the first time that retinopathy has been linked to severe C19 in people with diabetes. Retinopathy is a marker of damage to the blood vessels and our results suggest that such pre-existing damage to blood vessels may result in a more severe C19 infection requiring intensive care treatment.
- Senior author, Dr Janaka Karalliedde from King’s College London, said: “There is increasing evidence that there is significant damage to the blood vessels in the lung and other organs in patients hospitalized with severe C19. People with diabetes are at high risk of vascular complications affecting the large and small blood vessels.
- “We hypothesize that the presence of diabetes related vascular disease such as retinopathy may result in greater vulnerability and susceptibility to respiratory failure in severe C19. Therefore looking for presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe C19. Further studies are required to investigate the possible mechanisms that explain the links between markers and manifestations of diabetic vascular disease such as retinopathy and severe C19.”
- RNIB Specialist Lead for Eye Health, Dr Louise Gow said: “RNIB hope this research will result in greater awareness of those who are most at risk of serious complications from C19. With vaccine planning underway, consideration must be given to prioritizing people with diabetic retinopathy. It also highlights that it is vital that information about C19 is available in formats that are accessible to people with sight loss so that they know how to protect themselves.”
2. C19 infection combined with blood clots worsen patient outcomes
- While respiratory issues continue to be the most common symptom of a C19 infection, new research indicates the disease could also be associated with hypercoagulability, or increased tendency of the blood to clot. In a new study published November 20, 2020 in the journal EClinical Medicine by The Lancet, researchers from UC San Diego Health found that blood clots led to an increased risk of death by 74%.
- Led by Mahmoud Malas, MD, division chief of Vascular and Endovascular Surgery at UC San Diego Health, researchers reviewed 42 different studies involving more than 8,000 patients diagnosed with C19. Using random models, the team produced summary rates and odds ratios of mortality in C19 patients with thromboembolism, blood clots — and compared them to patients without these conditions to determine what effect blood clots may have on risk of death.
- “We began to notice a really unusual manifestation of venous and arterial thromboembolism in patients with C19,” said Malas. “In addition to higher instances of blood clots, the mortality for patients hospitalized for C19 and with thromboembolism was much higher, compared to patients without clots. It’s unusual because we have never seen anything like this with other respiratory infections.”
- Overall, 20% of the C19 patients were found to have blood clots in the veins, and among patients in the intensive care unit, that statistic increased to 31%.
- Blood clots in the vein, or deep vein thrombosis, can reach the lungs and develop into pulmonary embolism, resulting in higher risk of death. Blood clots in the arteries may lead to limb amputation if not treated surgically in a timely fashion.
- In the study, Malas and colleagues performed a systemic review through meta-analysis, which is a statistical method that allowed researchers to combine multiple studies to produce a single comprehensive paper.
- “The collective experience in the literature as captured in this meta-analysis study brings additional light on the importance of blood vessel clotting events in hospitalized patients with C19,” said Bryan Clary, MD, surgeon-in-chief at UC San Diego Health and co-author of the study. “While the frequency of these events is much higher than expected, our study likely underestimates the incidence of thromboembolism in the global population of patients with C19, including non-hospitalized patients.”
- According to Malas, arterial blood clots developing in people with the flu is extremely rare, and the rate of clotting in patients with C19 is higher than what is reported for other viral pandemics, including the H1N1 influenza of 2009.
- Similar symptoms are shared between influenza and SARS-CoV-2, such as fever, cough, shortness of breath, or fatigue. Blood clotting can occur in patients hospitalized with the flu, but only in veins. For patients with C19, blood clots can appear in either veins or arteries.
- Typically, clotting in the arteries is caused by health factors, such as atrial fibrillation, high blood pressure, high cholesterol, diabetes, or lifestyle choices like smoking. Patients who are hospitalized for long periods of time are also more at risk for blood clots in the vein due to immobility.
- Blood clots in the vein are treated or prevented with prescribed blood thinners. Proactively administering such medications to hospitalized patients can also help prevent clots from forming. Clinical trials are ongoing to determine how blood thinners can reduce the risk of clotting in patients with C19.
- “What we can learn from this paper is due diligence,” said Malas. “We’re still in the process of understanding the pathophysiology of C19, so it’s important to have a low index of suspicion when it comes to this infection to ensure we’re doing all we can to mitigate the spread and prevent severe outcomes.”
3. High blood sugar could increase C19 death risk for non-diabetics
- A study, based on more than 11,000 non-critically ill hospital patients in Spain, is the largest of its kind to date. It adds to evidence that hyperglycaemia – the medical term for high blood glucose – is associated with a higher chance of death independent of a diabetes diagnosis.
- The findings show patients with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% compared to 15.7%). They also had an increased need for a ventilator and intensive care admission (ICU).
- The researchers are now calling for compulsory hyperglycemia screening and early treatment for anyone hospitalized with C19 who is non-diabetic. They urge clinicians not to overlook the condition among patients, regardless of a prior history of diabetes.
- “Screening for hyperglycaemia in patients without diabetes and early treatment should be mandatory in the management of patients hospitalized with C19,” says study coordinator Dr Javier Carrasco from Juan Ramon Jimenez University Hospital.
- “Admission hyperglycaemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of C19 patients with and without diabetes.”
- Hyperglycaemia is a common problem for diabetics but can also be triggered by illness or injury. Studies have previously linked acute cases with complications in diabetic and non-diabetic hospital patients, and observed similar associations among people with C19.
- In this study, the aim was to investigate a link between hyperglycaemia and time spent in hospital, mechanical ventilation, ICU admission and mortality, but independent of a diabetes diagnosis.
- Data was analyzed from a national registry which has been collating information from more than 100 hospitals in Spain during the pandemic. A total of 11,312 patients were included aged 18 or above who were admitted from March to the end of May.
- They were categorized into three groups relating to their blood glucose levels and ranging from normal to high (<140 mg/dl; 140-180 mg/dl; and> 180 mg/dl). A total of 19% had an existing diabetes diagnosis.
- The findings showed that patient blood glucose levels as measured on arrival in hospital were independently related to ICU admission, mechanical ventilation and/or death, regardless of diabetes status.
- One in five patients died in hospital, with mortality rates highest among those with the greatest blood glucose levels. No difference was found between death rates for those with diabetes and those who did not have the disease.
- The authors do caution that most patients did not have their average blood glucose level measured over a period of time. Therefore, some classed as non-diabetic could have had the disease without knowing.
- Exactly why hyperglycaemia is linked with higher death rates remains unclear. The researchers say the condition could be another ‘inflammatory bystander’ or have a more direct effect on how COVID leads to complications and death.
4. Adipose tissue (fat cells) may be the source of inflammatory factors that aggravate C19
- There is growing evidence that adipose tissue plays a key role in the aggravation of C19. One of the theories under investigation is that fat cells (adipocytes) act as a reservoir for the coronavirus (SARS-CoV-2) and increase viral load in obese or overweight individuals. Scientists also suspect that during infection fat cells release into the bloodstream substances that boost the inflammatory reaction triggered by the virus in the organism.
- These hypotheses are being investigated by researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil under the coordination of Marilia Cerqueira Leite Seelaender, a professor in the Department of Clinical Surgery. Peter Ratcliffe, a professor at the University of Oxford in the UK and one of the winners of the 2019 Nobel Prize for Medicine, is collaborating.
- “A cytokine storm resulting in systemic inflammation similar to sepsis occurs in some severe C19 patients. We believe these inflammatory factors come from adipose tissue. It’s been shown that when adipocytes expand too much, they can cause inflammation throughout the body, even in the brain,” Seelaender told Agência FAPESP.
- The FM-USP group analyzed samples of adipose tissue obtained from autopsies of people who died from C19, and also from patients infected with SARS-CoV-2 who had to be submitted to emergency surgery at the university’s hospital for appendicitis or other reasons not related to the viral infection. Preliminary results confirmed that the virus can be found in fat cells, whose membranes are rich in ACE-2, the main receptor used by the virus to invade human cells. The researchers have yet to confirm that once it has invaded adipocytes, it can remain there long enough to replicate inside them.
- “It’s worth noting that visceral adipocytes [located deep in the abdomen and around internal organs] have much more ACE2 than subcutaneous adipose tissue,” Seelaender said. “In addition, they’re much more inflammatory. As a result, visceral obesity tends to be even more harmful as far as C19 is concerned.”
- The preliminary findings also brought to light a change in the pattern of exosome secretion in the adipose tissue of infected people. Exosomes are extracellular vesicles, comparable to tiny bubbles, released by cells into the bloodstream with proteins and other types of signaling molecules. This is one of the mechanisms whereby information is exchanged between different tissues as the body adapts to changes in its environment.
- The aims of the research conducted by the FM-USP group include investigating whether infection by SARS-CoV-2 makes adipocytes release more exosomes containing inflammatory factors. So far it has shown that the number of vesicles released into the bloodstream does indeed increase. The researchers will now analyze the contents of these circulating vesicles, as well as those remaining inside cells. They also plan to investigate the inflammatory pathways presumably activated by these molecules.
- “We first assumed that as a person gets fat, their adipose tissue becomes hypoxic, meaning the person has less oxygen available. Hypoxia is itself a cause of inflammation, so one of the things we want to investigate is whether C19 causes hypoxia in adipocytes,” Seelaender said.
- Research on how human cells adapt to hypoxia won Ratcliffe the Nobel with William G. Kaelin (Harvard University) and Gregg Semenza (Johns Hopkins School of Medicine).
- Sir Radcliffe’s group is now interested in exploring the possibility that the SARS-CoV-2 virus interacts with hypoxia signalling pathways, and the Brazilian and British groups are collaborating as to address this hypothesis.
- The FM-USP group, meanwhile, is concentrating on an effort to understand the effect of infection on adipose tissue. “We’re analyzing everything secreted by fat cells: proteins, saturated fatty acids, prostaglandins [lipids with diverse hormone-like effects], microRNAs [small non-coding RNA molecules that regulate gene expression] and exosomes,” Seelaender said.
- Inflammatory factors released by adipose tissue in C19 patients may be the cause of damage to the heart, lungs, and nervous system described in such patients, she added. “Our hypothesis is that obese C19 patients undergo a similar process to that observed in the adipose tissue of patients with cachexia [significant rapid weight loss and muscle wasting associated with AIDS, heart failure and cancer, among other diseases],” she said. “Adipocytes in cachexic individuals release more exosomes, and their contents are altered so that they have a pro-inflammatory profile. We know there’s inflammation in both cachexia and obesity. The difference lies in the type of inflammatory mediator released and the signaling pathways activated.”
- Seelaender and her group have been researching the links between cachexia and inflammation since 2013 with FAPESP’s support.
Opposite but similar
- In an article published in the journal Advances in Nutrition, Seelaender and her group discuss how nutritional status can influence a patient’s response to C19. According to the authors, both obesity and malnutrition – including cachexia and sarcopenia (loss of skeletal muscle mass associated with aging) – can impair the immune response and prevent the organism from combating viral infection.
- “Immune cells require more energy during an infectious process, especially if the body takes a long time to overcome it. Their metabolism needs to change so that they can multiply rapidly, but in an undernourished organism, this isn’t possible. During an infection the number of T-lymphocytes in a malnourished individual is much smaller than in a eutrophic [well-nourished] individual,” Seelaender said.
- Moreover, she continued, undernourished organisms suffer from atrophy of the lymphoid organs (especially bone marrow, thymus and lymph nodes), in which the lymphocytes are produced and reach maturity. As a result, the number of circulating defense cells declines. Experiments with animals have also shown that an organism suffering from malnutrition takes longer to eliminate viruses.
- “Fat can be a problem when it’s excessive or insufficient. However paradoxical it may seem, both extremes are dangerous,” she explained. “Adipose tissue secretes leptin, a hormone that regulates T-lymphocyte metabolism. Leptin signaling falls in a body with very low fat. Excessively high fat makes cells less sensitive to leptin, so the amount of leptin released rises sharply.”
- Aging affects several of the factors mentioned by Seelaender. The immune system becomes less responsive. Skeletal muscle mass dwindles, visceral fat increases, and the proportion between lean and fat mass worsens.
- “Loss of lean mass can worsen the outcome of chronic and acute diseases in older people. Muscle is a reservoir of energy substrate [amino acids] that can be mobilized at times of need, such as during an infection,” she said. “That’s why it’s important to stress that not just adiposity but also the lean-to-fat mass ratio is a problem in C19 patients. If a person has a lot of fat and little muscle, it’s worse than if they have a lot of fat but a good muscular condition.”
5. Small Gatherings Spread the Virus, but Are They Causing the Surge?
- As states struggle to contain the resurgent coronavirus, many officials are laying the blame on an unexpected source: people gathering with family and friends.
- Household get-togethers undoubtedly do contribute to community transmission of the virus. Canada’s recent Thanksgiving certainly added to its rising cases; such an increase may happen here, too, as the United States embarks on a holiday season like no other. That’s why the Centers for Disease Control and Prevention on Thursday warned so strongly against gathering with others outside the household during Thanksgiving.
- But are dinners and backyard barbecues really the engine driving the current surge of infections? The available data do not support that contention, scientists say. Still, the idea has been repeated so often it has become conventional wisdom, leading to significant restrictions in many states.
- In dozens of statements over the past weeks, political leaders and public health officials have said that while previous waves of infection could be linked to nursing homes, meatpacking plants or restaurants, the problem now is that unmasked people are sitting too closely in kitchens and living rooms, lighting thousands of small Covid fires that burn through their communities.
- “It’s those informal, private gatherings where we’re seeing the ignition taking off in terms of the infection rate,” Gov. Ned Lamont of Connecticut said earlier this month, as he announced that private events would be restricted to 10 people.
- Household gatherings have “become a major vector of disease spread,” the Health and Human Services secretary, Alex Azar, said in an interview with CNN in late October.
- But many epidemiologists are far less certain, saying there is little evidence to suggest that household gatherings were the source of the majority of infections since the summer. Indeed, it has become much harder to pinpoint any source of any outbreak, now that the virus is so widespread and Americans may be exposed in so many ways.
- “Somebody says something, and somebody else says it, and then it just becomes truth,” said Julia Marcus, an infectious disease epidemiologist at Harvard University. “I worry about this narrative that doesn’t yet seem to be data-based.”
- Most states don’t collect or report detailed information about the exposure that led to a new infection. But in states where a breakdown is available, long-term care facilities, food processing plants, prisons, health care settings, and restaurants and bars are still the leading sources of spread, the data suggest.
- An analysis of nearly 800 nursing homes in six states experiencing the biggest surges, including North Dakota, South Dakota and Wisconsin, found that these homes are still hot spots of viral transmission and that little has been done since the spring to reduce that risk.
- It is nearly impossible to compare the relative contribution of social gatherings to the number of cases in different states, or even to find a consistent definition of what constitutes a gathering.
- Rhode Island, which limited private gatherings to 10 people, helpfully defined the term, including family get-togethers, birthday parties, baby showers and sleepovers. But some states also add larger events, such as weddings and funerals, into the category.
- These gatherings, especially if held indoors, certainly can drive infections. In rural Maine, a wedding with 55 guests ultimately resulted in 177 cases, while a wedding in Washington State led to at least 17. Outbreaks in communities with tight-knit social networks, such as the Amish and the Hasidic Jewish population, were also powered by large social events.
- But the same cannot be said of smaller private gatherings with friends and family. In Colorado, only 81 active cases are attributed to social gatherings, compared with more than 4,000 from correctional centers and jails, 3,300 from colleges and universities, nearly 2,400 from assisted living facilities, and 450 from restaurants, bars, casinos and bowling alleys.
- In Louisiana, social events account for just 1.7 percent of the 3,300 cases for which the state has clear exposure information.
- “It’s important to give good public health advice about what’s coming in the holidays, no doubt about it,” said Dr. Tom Inglesby, director of the Center for Health Security at Johns Hopkins Bloomberg School of Public Health. “But it is not good to suggest that they are now the preponderance of the source of spread.”
- Social gatherings have become a convenient scapegoat for political leaders flummoxed by the steeply climbing numbers, some experts said.
- “It seems like they’re passing off the responsibility for controlling the outbreak to individuals and individual choices,” said Ellie Murray, an epidemiologist at Boston University. “A pandemic is more a failure of the system than the failure of individual choices.”
- A similar narrative played out in September, when universities shamed and expelled students for partying instead of providing them with clear guidelines and resources, Dr. Marcus said.
- “It’s a way of distracting from the harder public health work that we need to do,” she said — for example, by implementing mask mandates, addressing societal inequities and ensuring enough personal protective equipment for health care workers.
- (A recent analysis by The New York Times showed that states where leaders did not impose these containment measures now have the worst outbreaks.)
- A constant drumbeat about the dangers of social gatherings may help to convey the seriousness of the current surge, she said. On the other hand, in some states the misperception has led to draconian policies that don’t square with science.
- Gov. Tim Walz of Minnesota on Wednesday took the extraordinary step of banning people from different households from meeting indoors or outdoors, even though evidence has consistently shown the outdoors to be relatively safe.
- But the executive order allows places of worship, funeral homes and wedding venues — while they are encouraged to hold virtual events — to host as many as 250 people indoors.
- Vermont likewise forbade people from meeting neighbors for a socially distanced and masked walk, but permitted them to dine indoors at restaurants before 10 p.m.
- These recommendations are unscientific and “bizarre,” said Ashleigh Tuite, an infectious disease modeler at the University of Toronto.
- “If people are going to meet up, doing so outdoors is probably the lowest-risk way to do it,” she said. “Telling people they can’t spend time safely outdoors isn’t a rational approach. People are going to recognize that and push back.”
- (On Friday, following public complaints, Gov. Phil Scott of Vermont said people from different households could walk together as long as they wore masks and stayed more than six feet apart.)
- Dissonant policies also run the risk of fueling mistrust and resentment in a public already beset with fatigue from the pandemic and politics, Dr. Tuite warned.
- “If you’re an average person looking at what’s allowed and what’s not allowed, it may not make a lot of sense,” she said. “I can get together with nine of my best friends and sit around a table at a restaurant. So why can’t I do that in my house?”
- Cracking down on social gatherings suggests that there is clear evidence regarding where people are exposed and that they are meeting more often now than earlier in the pandemic. But the data are not clear: For example, the percentage of Californians who visited friends or had guests over at their homes has hovered around 50 percent since June, according to weekly surveys conducted by the University of Southern California.
- In most places, the virus is too widespread to claim with any confidence where someone became infected. Where once clusters were obvious — in nursing homes and meatpacking plants, for example — now there are thousands of small outbreaks in restaurants, bars, bowling alleys, colleges and gyms.
- “It really feels like there’s just little fires all over the place,” said Dr. K.J. Seung, chief of strategy and policy for Covid-19 response in Massachusetts. “There’s more of these social gathering clusters, there’s more workplace clusters, there’s more church clusters, there’s more youth sports clusters — more everything.”
- In this sort of conflagration, it’s impossible to estimate how much social gatherings contribute to community transmission.
- Maryland’s public health department has reported that 13 percent of people who were infected said they had attended at least one gathering of more than 10 people. “As an epidemiologist, I don’t know what to do with that information,” said Jennifer Nuzzo, an epidemiologist at Johns Hopkins Center for Health Security. “I don’t know just because they went there that they got it there.”
- In Minnesota, up to the week ending Nov. 12, there were about 202,000 coronavirus infections. Nearly 12,000 were attributed to restaurants, bars and sports sites, and about 17,000 to congregate care settings.
- Yet more than 115,000 of the cases could not be traced back to a known setting. “Identifying any one activity as the driver of the surge misses the fact that all activities become riskier as local case levels rise,” Dr. Murray said.
- “Household gatherings would be much safer if officials put stricter limits on commercial and nonresidential activities. They are choosing not to, and then saying the fault lies with individuals.”
- Local governments could also provide safer gathering spaces for people, with open-air tents, firepits and heat lamps as temperatures drop, Dr. Marcus said: “Then the message becomes a more realistic one. Instead of ‘don’t gather,’ it’s ‘gather here instead.’”
- A disproportionate emphasis on private gatherings does not make sense, Dr. Marcus added: “We need to be putting our attention where it’s most needed, and I’m not convinced that this is where it’s most needed.”
6. C19 Data Is a Mess. We Need a Way to Make Sense of It.
- The United States is more than eight months into the pandemic and people are back waiting in long lines to be tested as coronavirus infections surge again. And yet there is still no federal standard to ensure testing results are being uniformly reported. Without uniform results, it is impossible to track cases accurately or respond effectively.
- We test to identify coronavirus infections in communities. We can tell if we are casting a wide enough net by looking at test positivity — the percentage of people whose results are positive for the virus. The metric tells us whether we are testing enough or if the transmission of the virus is outpacing our efforts to slow it.
- If the percentage of tests coming back positive is low, it gives us more confidence that we are not missing a lot of infections. It can also tell us whether a recent surge in cases may be a result of increased testing, as President Trump has asserted, or that cases are rising faster than the rate at which communities are able to test.
- But to interpret these results properly, we need a national standard for how these results are reported publicly by each state. And although the CDC has issued protocols for how to report new cases and deaths, there is no uniform guideline for states to report testing results, which would tell us about the universe of people tested so we know we are doing enough testing to track the disease. (Even the CDC was found in May to be reporting states’ results in a way that presented a misleading picture of the pandemic.)
- Without a standard, states are deciding how to calculate positivity rates on their own — and their approaches are very different.
- Some states include results from positive antigen-based tests, some states don’t. Some report the number of people tested, while others report only the number of tests administered, which can skew the overall results when people are tested repeatedly (as, say, at colleges and nursing homes).
- At one point in the spring, Texas, Virginia and Vermont were accused of reporting their data so that it inflated the scale of their testing programs and made it impossible to determine how many active infections they were probably missing. The problem has since been corrected.
- Only seven states and the District of Columbia report testing data by race and ethnicity — indicators that can often point to virus trouble spots in some of the nation’s poorest communities. Many states have also changed how and when they report their testing data. This has led to wild swings in reported test positivities that have nothing to do with the virus’s spread.
- Last week, the governor of New York and the mayor of New York City disagreed on whether a threshold of 3% positivity had been breached in the city. The mayor said it had and closed the schools; the governor said it had not. “The cause of the discrepancy,” according to The Times, lay “in both the tests that are included and the time frame in which statistics are reported.” This inconsistency can be the difference between shutting down schools and indoor dining, for instance, or not.
- Inconsistent data also limits how reliably positivity can serve as an early warning about demand for hospital beds and medical equipment. Making informed comparisons between states requires having similar data to compare.
- Without a federal standard, the data also becomes more susceptible to political influence. By deciding how many tests to offer and prioritizing certain groups for testing, local officials can artificially slow rising positivity rates. Recently, suspicions were raised among public health officials in New York when skyrocketing positivity in one community suddenly reversed course.
- C19 is surging and hospital capacity is again being stretched. Disparities are deepening, with Black and Latino patients more likely to be hospitalized and die from C19. Since May, our institution, Johns Hopkins, has generated state-by-state positivity calculations, and it is clear to us that the lack of reporting standards for testing data is hindering the U.S. response to the virus.
- This is inexcusable. As the pandemic accelerates to new levels of transmission every day, we urgently need a federal standard to guide testing and inform public health responses. That’s the reason we test and track the results in the first place.
7. Can dogs smell COVID?
- Asher is an eccentric, Storm likes sunbathing and Maple loves to use her brain. All three could play a part in controlling the C19 pandemic, but they are not scientists or politicians. They are dogs.
- And they are not alone. Around the world, canines are being trained to detect the whiff of C19 infections. Dog trainers are claiming extraordinary results — in some cases, they say that dogs can detect the virus with almost perfect accuracy.
- Scientists involved with the efforts suggest that canines could help to control the pandemic because they can screen hundreds of people an hour in busy places such as airports or sports stadiums, and are cheaper to run than conventional testing methods such as the RNA-amplification technique PCR.
- But most of these findings have not yet been peer reviewed or published, making it hard for the wider scientific community to evaluate the claims. Researchers working on more conventional viral tests say that initial results from dog groups are intriguing and show promise. But some question whether the process can be scaled up to a level that would allow the animals to make a meaningful impact.
- On 3 November, groups working with the animals met in an online workshop called International K9 Team to share preliminary results from experiments and to improve how their research is coordinated.
- “No one is saying they can replace a PCR machine, but they could be very promising,” says veterinary neurologist Holger Volk at the University of Veterinary Medicine Hanover in Germany, who is leading an effort to train and study COVID-sniffing dogs and did not speak at the event.
Sense of wonder
- Humans have taken advantage of canines’ superior sense of smell for decades. Dogs’ noses bear 300 million scent receptors, compared with humans’ 5 million or 6 million. That enables them to detect tiny concentrations of odor that people can’t. Sniffer dogs are already a familiar sight in airports, where they detect firearms, explosives and drugs.
- Scientists have also trained dogs to detect some cancers and malaria, but the animals are not routinely used for this purpose. Researchers don’t know for sure what the dogs are smelling, but many suspect that these illnesses cause the human body to let off a distinct pattern of volatile organic compounds (VOCs). These molecules readily evaporate to create scent that dogs can pick up. Previous work with non-COVID viruses has suggested that viral infections might also cause the body to do this.
- Many sniffer-dog scientists turned their attention to C19 early in the pandemic. They have trained their canines to smell samples, most often of sweat, in sterile containers, and to sit or paw the floor when they detect signs of infection. Trials at airports in the United Arab Emirates, Finland and Lebanon are using dogs to detect C19 in sweat samples from passengers; these are then checked against conventional tests. According to data presented at the K9 meeting, dogs in Finland and Lebanon have identified cases days before conventional tests picked up the virus, suggesting that dogs can spot infection before symptoms start.
- Riad Sarkis, a surgeon and researcher at Saint Joseph University in Beirut, is part of a French–Lebanese project that has trained 18 dogs. Sarkis used the best two performers for the airport trial in Lebanon. The dogs screened 1,680 passengers and found 158 C19 cases that were confirmed by PCR tests.
- The animals correctly identified negative results with 100% accuracy, and correctly detected 92% of positive cases, according to unpublished results. “This is very accurate, feasible, cheap and reproducible,” says Sarkis, who has been approached about using the dogs in schools, banks and prisons, and is working with a shopping mall to offer C19 testing using the animals.
- Low-income countries with limited lab space could particularly benefit from the approach, says Isabella Eckerle, a virologist at the University Hospitals of Geneva in Switzerland.
- But there is just one published journal article on dogs’ efficacy at sniffing out C19, by Volk’s group; he describes it as a pilot study. The researchers trained eight dogs on samples taken from the mouths and windpipes of seven people hospitalized with C19 and seven uninfected people. The dogs identified 83% of positive cases and 96% of negative ones.
- The false positive and negative rates of the standard PCR lab test vary depending on the brand of test used and the timing of the test. A systematic review published as a preprint on medRxiv found the false-negative rate of RT-PCR tests to be 2–33% if the same sample is tested repeated times. Up to 4% of UK PCR test results could be false positives, according to government documents.
- Critics say the German dog study used samples from too few patients. The dogs could be learning to identify the specific scent of the samples rather than of C19, says Cynthia Otto, who leads the Penn Vet Working Dog Centre at the University of Pennsylvania in Philadelphia and is also working with C19 sniffer dogs.
- In her work, which is also unpublished, she has found that the dogs can tell the difference between samples of either urine or sweat from people with C19 and those from people without the disease. She is working with chemists to understand which VOCs the dogs are picking up; a paper describing this is under review. “The dogs can do it. The challenge is the ignorance that we have as humans as to what can confuse the dogs,” she says. And in an effort to gather a large data set, her team is collecting sweat samples from 1,000 T-shirts worn overnight by people who have tested positive and negative for C19.
- A group in France, led by veterinary scientist Dominique Grandjean at the National Veterinary School of Alfort near Paris, posted its work on the preprint server bioRxiv in June. The researchers, who included Sarkis, trained 8 dogs to detect C19 in 198 sweat samples, around half of which were from people with the disease. When these were hidden in a row of negative samples, the dogs identified the positive samples 83–100% of the time. The paper does not say how well the dogs identified negative test results. The research is now under review at a journal, but Grandjean says the process has not been easy. “To publish papers on detection dogs is very difficult because most reviewers do not know anything about working dogs,” he says.
- The data in that study look promising, says Fyodor Urnov, a gene-editing scientist who is working on COVID testing at the University of California, Berkeley. But he would like to see larger data sets on how well dogs identify positive and negative samples. He also notes that there is variation in how well individual dogs perform. In Grandjean’s study, for example, 2 dogs identified 68 out of 68 positive samples, whereas one missed 10 out of 57 cases.
- Groups need to boost their sample sizes before the wider scientific community can evaluate how useful the dogs might be, agrees James Logan, an infectious-disease researcher at the London School of Hygiene & Tropical Medicine who is training and studying C19 dogs, including Storm, Maple and Asher. “It’s important not to go out too early with grand claims and small data sets,” he says.
G. The Road Back?
1. The Best and Worst Places to Be in the Coronavirus Era
- As C19 has spread around the world, it’s challenged preconceptions about which places would best tackle the worst public health crisis in a generation.
- Advanced economies like the U.S. and U.K., ranked by various pre-2020 measures as being the most prepared for a pandemic, have been repeatedly overwhelmed by infections and face a return to costly lockdowns. Meanwhile, other countries—even developing nations—have defied expectations, some all but eliminating the pathogen within their borders.
- Bloomberg crunched the numbers to determine the best places to be in the coronavirus era: where has the virus been handled most effectively with the least amount of disruption to business and society?
- For a deep analysis of how countries have fared around the world, click on the link below.
2. Hospitals Know What’s Coming
- Perhaps no hospital in the United States was better prepared for a pandemic than the University of Nebraska Medical Center in Omaha.
- After the SARS outbreak of 2003, its staff began specifically preparing for emerging infections. The center has the nation’s only federal quarantine facility and its largest biocontainment unit, which cared for airlifted Ebola patients in 2014. The people on staff had detailed pandemic plans. They ran drills. Ron Klain, who was President Barack Obama’s “Ebola czar” and will be Joe Biden’s chief of staff in the White House, once told me that UNMC is “arguably the best in the country” at handling dangerous and unusual diseases. There’s a reason many of the Americans who were airlifted from the Diamond Princess cruise ship in February were sent to UNMC.
- In the past two weeks, the hospital had to convert an entire building into a C19 tower, from the top down. It now has 10 C19 units, each taking up an entire hospital floor. Three of the units provide intensive care to the very sickest people, several of whom die every day. One unit solely provides “comfort care” to C19 patients who are certain to die. “We’ve never had to do anything like this,” Angela Hewlett, the infectious-disease specialist who directs the hospital’s C19 team, told me. “We are on an absolutely catastrophic path.”
- To hear such talk from someone at UNMC, the best-prepared of America’s hospitals, should shake the entire nation. In mid-March, when just 18 Nebraskans had tested positive for C19, Shelly Schwedhelm, the head of the hospital’s emergency-preparedness program, sounded gently confident. Or, at least, she told me: “I’m confident in having a plan.” She hoped the hospital wouldn’t hit capacity, “because people will have done the right thing by staying home,” she said. And people did: For a while, the U.S. flattened the curve.
- But now about 2,400 Nebraskans are testing positive for C19 every day—a rate five times higher than in the spring. More than 20 percent of tests are coming back positive, and up to 70% in some rural counties—signs that many infections aren’t being detected. The number of people who’ve been hospitalized with the disease has tripled in just six weeks. UNMC is fuller with C19 patients—and patients, full stop—than it has ever been. “We’re watching a system breaking in front of us and we’re helpless to stop it,” says Kelly Cawcutt, an infectious-disease and critical-care physician.
- Cawcutt knows what’s coming. Throughout the pandemic, hospitalizations have lagged behind cases by about 12 days. Over the past 12 days, the total number of confirmed cases in Nebraska has risen from 82,400 to 109,280. That rise represents a wave of patients that will slam into already beleaguered hospitals between now and Thanksgiving. “I don’t see how we avoid becoming overwhelmed,” says Dan Johnson, a critical-care doctor. People need to know that “the assumption we will always have a hospital bed for them is a false one.”
- Not even the best-prepared hospital can compensate for an unchecked pandemic. UNMC’s preparations didn’t fail so much as the U.S. created a situation in which hospitals could not possibly succeed. “We can prepare over and over for a wave of patients,” says Cawcutt, “but we can’t prepare for a tsunami.”
- A full hospital means that everyone waits. C19 patients who are going downhill must wait to enter a packed intensive-care unit. Patients who cannot breathe must wait for the many minutes it takes for a nurse elsewhere in the hospital to remove cumbersome protective gear, run over, and don the gear again. On Tuesday, one rapidly deteriorating patient needed to be intubated, but the assembled doctors had to wait, because the anesthesiologists were all busy intubating four other patients in an ICU and a few more in an emergency room.
- None of the people I spoke with would predict when UNMC will finally hit its capacity ceiling, partly because they’re doing everything to avoid that scenario, and partly because it’s so grim as to be almost unthinkable. But “we’re rapidly approaching that point,” Hewlett said.
- When it arrives, people with C19 will die not just because of the virus, but because the hospital will have nowhere to put them and no one to help them. Doctors will have to decide who to put on a ventilator or a dialysis machine. They’ll have to choose whether to abandon entire groups of patients who can’t get help elsewhere. While cities like New York and Boston have many big hospitals that can care for advanced strokes, failing hearts that need mechanical support, and transplanted organs, “in this region, we’re it,” Johnson says. “We provide care that can’t be provided at any other hospital for a 200-mile radius. We’re going to need to decide if we continue to offer that care, or if we admit every single C19 patient who comes through our door.”
- During the spring, most of UNMC’s C19 patients were either elderly people from nursing homes or workers in meatpacking plants and factories. But with the third national surge, “all the trends have gone out the window,” Sarah Swistak, a staff nurse, told me. “From the 90-year-old with every comorbidity listed to the 30-year-old who is the picture of perfect health, they’re all requiring oxygen because they’re so short of breath.”
- This lack of pattern is a pattern in itself, and suggests that there’s no single explanation for the current surge. Nebraska reopened too early, “when we didn’t have enough control, and in the absence of a mask mandate,” Cawcutt says. Pandemic fatigue set in. Weddings that were postponed from the spring took place in the fall. Customers packed into indoor spaces, like bars and restaurants, where the virus most easily finds new hosts. Colleges resumed in-person classes. UNMC is struggling not because of any one super-spreading event, but because of the cumulative toll of millions of bad decisions.
- When the hospital first faced the pandemic in the spring, “I was buoyed by the realization that everyone in America was doing their part to slow down the spread,” Johnson says. “Now I know friends of mine are going about their normal lives, having parties and dinners, and playing sports indoors. It’s very difficult to do this work when we know so many people are not doing their part.” The drive home from the packed hospital takes him past rows of packed restaurants, sporting venues, and parking lots.
- To a degree, Johnson sympathizes. “I don’t think people in Omaha thought we could ever have something that resembles New York,” he told me. “To be honest, in the spring, I would have thought it extremely unlikely.” But he adds that the Midwest has taken entirely the wrong lesson from the Northeast’s ordeal. Instead of learning that the pandemic is controllable, and that physical distancing works, people instead internalized “a mistaken belief that every curve that goes up must come down,” he said. “What they don’t realize is that if we don’t change anything about how we’re conducting ourselves, the curve can go up and up.”
- Speaking on Tuesday afternoon, Nebraska Governor Pete Ricketts once again refused to issue a statewide mask mandate. He promised to tighten restrictions once a quarter of the state’s beds are filled with C19 patients, but even then, some restaurants will still offer indoor dining; gyms and churches will remain open; and groups of 10 people will still be able to gather in enclosed spaces. Ricketts urged Nebraskans to avoid close contact, confined areas, and crowds, but his policies nullify his pleas. “People have the mistaken belief that if the government allows them to do something, it is safe to do,” Johnson said.
- There are signs that citizens and businesses are acting ahead of policy makers. Some restaurants are ceasing indoor dining even without a prohibition. Parents are pulling their children out of schools and sports leagues. “I have heard from more friends and family about C19 in the last two weeks than I have in the previous six months, expressing support and a change in attitudes,” Johnson said.
- But C19 works slowly. It takes several days for infected people to show symptoms, a dozen more for newly diagnosed cases to wend their way to hospitals, and even more for the sickest of patients to die. These lags mean that the pandemic’s near-term future is always set, baked in by the choices of the past. It means that Ricketts is already too late to stop whatever UNMC will face in the coming weeks (but not too late to spare the hospital further grief next month). It means that some of the people who get infected over Thanksgiving will struggle to enter packed hospitals by the middle of December, and be in the ground by Christmas.
- Officially, Nebraska has 4,223 hospital beds, of which 1,165—27 percent—are still available. But that figure is deceptive. It includes beds for labor and deliveries, as well as pediatric beds that cannot be repurposed. It also says nothing about how stretched hospitals have already become in their efforts to create capacity. UNMC has postponed elective surgeries—those which could be deferred for four to 12 weeks. Patients with strokes and other urgent traumas aren’t getting the normal level of attention, because the pandemic is so all-consuming. Clinical research has stopped because research nurses are now C19 nurses. The hospital is forced to turn down many requests to take in patients from rural hospitals and neighboring states that are themselves almost out of beds.
- Empty hospital beds might as well be hotel beds without doctors and nurses to staff them. And though health-care workers are resilient, “many of us feel like we haven’t had a day off since this thing began,” Hewlett says. The current surge is pushing them to the limit because people with C19 are far sicker than the average patient. In an ICU, they need twice as much attention for three times the usual stay. To care for them, UNMC’s nurses and respiratory therapists are now doing mandatory overtime. The hospital has tried to hire travel nurses, but with the entire country calling for help, the pool of reinforcements is dry. “Even before C19 hit, we were short-staffed,” says Becky Long, a lead nurse on a COVID ICU floor. Of late, there have been days when the hospital had 45 to 60 fewer nurses than it needed. “Every time I’ve been at work, I’ve thought: This is going to be the final straw. But somehow we continue to make it work, and I truly have no idea how.”
- Before C19, Long worked in oncology. Death is no stranger to her, but she tells me she can barely comprehend the amount she has seen in recent weeks. “I used to be able to leave work at work, but with the pandemic, it follows me everywhere I go,” she said. “It’s all I see when I come home, when I look at my kids.”
- Long and other nurses have told many families that they can’t see their dying loved ones, and then sat with those patients so they didn’t have to die alone. Lindsay Ivener, a staff nurse, told me that C19 had recently killed an elderly woman whom she was caring for, the woman’s husband, and one of her grandchildren. A second grandchild had just been admitted to the hospital with C19. “It just tore this whole family apart in a month,” Ivener said. “I couldn’t even cry. I didn’t have the energy.”
- Until recently, Ivener worked in corporate America as a retail buyer and inventory manager. Wanting to help people, she retrained as a nurse and graduated this May. “I’ve only worked as a nurse during a pandemic,” she told me. “It’s got to get better, right?”
H. Mortality Rates
1. Coronavirus survival rates in the US haven’t improved since summer
- Some Americans downplaying the novel coronavirus insist improved treatments have made the virus far less deadly than last spring.
- But that’s a far too rosy take.
- It’s true that better treatments are now available, but their impact isn’t nearly big enough to avoid an impending surge of deaths, expected to soon exceed 2,000 a day in the United States. And while the case fatality rate declined early in the pandemic, it hasn’t budged since the summer.
- “It’s been rock solid stable since July, around 1.7%,” said David Dowdy, an associate professor at the Johns Hopkins Bloomberg School of Public Health. “If anything, I think there is a concern it will go up again because we’re seeing hospitals reaching their capacity.”
- Treatments have improved survival rates incrementally.
- There’s no doubt health providers have discovered best practices for treating seriously ill C19 patients since the onset of the pandemic, along with some new therapeutics. In the past two weeks the Food and Drug Administration has given emergency approval to two monoclonal antibody treatments, one from Eli Lilly and another from Regeneron Pharmaceuticals.
- The treatments are designed to prevent infected people from developing severe illness by imitating the body’s natural defenses. They’re given to non-hospitalized patients, typically those who are at increased risk for severe illness due to either age or an underlying condition. President Trump received monoclonal antibodies when he was treated for the coronavirus in October.
- “Monoclonal antibodies, which are concocted in laboratories, are proteins that mimic the immune system’s ability to attack the virus,” The Washington Post’s Laurie McGinley and Carolyn Y. Johnson explain. “In a clinical trial, the Regeneron drug reduced hospitalizations or emergency room visits when given to people at high risk of developing severe disease. It was also shown to reduce the amount of virus in people’s bodies.”
- In a call with reporters yesterday, top Trump administration officials said they’ll be shipping out enough of Regeneron’s antibodies treatment for 30,000 patients — and plan to ship out enough for another 50,000 patients next week.
- “If you have tested positive for C19 and are at high risk for severe disease, we may have treatment options that can help you,” Health and Human Services Secretary Alex Azar said.
- But the impact of better treatments is marginal.
- The U.S. case fatality rate — which is the number of people who die out of everyone diagnosed — was around 5 to 6% in the springtime. That’s partly because fewer people were being tested, so fewer cases overall were being detected. But health providers were also figuring out for the first time how to treat C19 patients in severe respiratory distress.
- Over the summer, as testing expanded and hospitals tried different drugs and procedures on patients, the case fatality rate in the United States declined to between 1.5 and 2%. And that’s where it has remained over the past three months or so.
- Trevor Bedform, a genomic epidemiologist at the Fred Hutchsinson Cancer Research Center, found there have been no improvements in the death rates since August. Since then, the death rate among those diagnosed with covid-19 has averaged 1.8%, he told The Atlantic.
- “This rate is a major improvement, down more than tenfold from the earliest days of the pandemic, when deaths were high and the extreme limits on coronavirus testing held down the number of diagnosed cases,” The Atlantic’s Alexis C. Madrigal and Whet Moser write. “But in this new phase of the pandemic, when testing is more widely available and a much higher proportion of cases are diagnosed to begin with, it is also terrible, terrible news.”
- The antibody treatments from Eli Lilly and Regeneron are the most promising treatments so far.
- But they’re in short supply and difficult to administer, so they’re not going to be a magic bullet for saving the nation from a massive death toll this winter.
- “They’re very expensive and difficult to ramp up and produce at scale,” Dowdy said. “Do I really think these will move the needle on case fatality on a national level? Probably not.”
Note: Mortality rates are often based on confirmed cases (as is true in this article). Although the number of persons infected is unknown because many are asymptomatic, estimates of the number of infected persons is much higher than the number of confirmed cases, which would mean that the actual mortality rate is significantly lower than the confirmed case fatality rate.
I. Innovation & Technology
1. PhD graduate develops sodium-coated mask that kills C19 droplets
- A recent Ph.D. graduate won an award Tuesday for creating a reusable face mask that appears to kill infectious pathogens like the coronavirus — using a simple coating of salt.
- Ilaria Rubino, who recently graduated from the University of Alberta, said salt can eradicate viruses and bacteria within 5 minutes of droplets landing on the face covering.
- The highly breathable mask “provides a safe and effective solution to prevent diseases globally” — and can also be worn repeatedly, unlike the current ones used by health care professionals that need to be replaced regularly, according to research published in Scientific Reports.
- Canadian nonprofit research group Mitacs presented Rubino with an “Outstanding Innovation” award for her masks, which she told Yahoo Canada she hopes to get into production by next year.
- The masks would also kill other infectious illnesses like the flu — and could eventually be used in filters in hospitals and office buildings, Rubino’s research said.
- Dr. Catherine Clase, an epidemiologist and associate professor of medicine at McMaster University in Hamilton, told the Canadian Press that the reusable covering would “decrease the footprint for making and distributing and then disposing of every mask.”
2. AI Detects C19 on Chest X-rays More Accurately and 10 Times Faster Than Specialized Radiologists
Algorithm outperformed thoracic radiologists in detecting C19
- Algorithm was trained, tested on the largest COVID-era dataset (17,002 X-ray images)
- Algorithm analyzed X-ray images of lungs about 10 times faster, 1-6% more accurately than individual specialized radiologists
- Algorithm is now publicly available for other researchers to continue to train it with new data
- System could also potentially flag patients for isolation and testing who are not otherwise under investigation for C19
- “It would take seconds to screen a patient and determine if they need to be isolated,” researcher says
3. Some Masks Will Protect You Better Than Others
Opinion by Dr Scott Gottlieb, Former Commissioner of the FDA
- A rush of travel for Thanksgiving will lead to new C19 outbreaks. Infection rates are accelerating, and a growing percentage of those hospitalized are over 65. Past waves prompted people to reduce their activity, but recent Google mobility data don’t show a big change in behavior. Yet many Americans could take one simple step to protect themselves: Buy a better mask.
- The widespread use of masks has become an unfortunate flashpoint in the political debate over how seriously to take Covid. Naysayers argue that the masks won’t protect you, so why bother wearing them? The premise is false, but the level of protection depends on the type of the mask.
- I was part of the discussion with the government in the spring around the merits of federal guidance recommending people wear masks when they go out. A lot of Covid spread comes from people who are asymptomatic and don’t know they are infected. The thinking was that if more people wore masks, that could reduce the spread. For these purposes, data showed that many types of face covering could reduce transmission.
- Back then, medical masks were in short supply. As a compromise, the public was advised to use cloth masks. The supply chain has since expanded, and while there are still some shortages of medical masks, health-care workers have dedicated supply chains. It’s time to revise the guidance to consumers.
- A cotton mask offers far less protection than a surgical mask. If a cloth mask is all you can find, buy a thick one. Snug-fitting masks made of cotton-polyester blends will generally offer more protection. But even a very good cloth mask may only be about 30% protective; scarf or bandanna, 10% or less.
- A surgical mask could offer you better protection, on the order of 60%. But here again, quality matters. Many of the masks sold on Amazon, which say they are for dust and allergens, aren’t surgical masks, even though they look like the blue masks worn by nurses and doctors. A real medical-procedure mask will be cleared by the Food and Drug Administration and designated as offering one of three levels of protection. Generally, a level 2 or level 3 medical mask is best.
- An N95 or equivalent mask offers the best protection and, if used properly, will filter out at least 95% of infectious particles. Online resources can help you fit the mask. In China the equivalent mask is the KN95 and in Europe the comparable designation is FFP2. The FDA has authorized for emergency use a bunch of KN95 and FFP2 masks that have been tested to show that they offer comparable protection to an N95 mask. These options are listed on the FDA’s website.
- Masks may also be evaluated by the National Institute for Occupational Safety and Health, a part of the Centers for Disease Control and Prevention that certifies masks for industrial uses. Check to see if your mask is listed in the Niosh database. Many products claim to be N95 equivalent but haven’t undergone testing and may be counterfeits.
- Better-quality masks can be expensive—perhaps $5 for a single N95 mask. But having a few available for high-risk settings such as the grocery store can reduce the risk of transmission. The Department of Homeland Security has published instructions online on disinfecting and reusing N95 masks that can extend their life.
- Governors can help: States can provide masks to people at high risk who can’t find them easily. They can also direct consumers to the best masks they can source. The FDA and CDC typically weigh in on the quality of masks when a manufacturer seeks federal review or sells a mask for medical use. But state agencies have more latitude to speak to the full range of products sold to consumers online.
- Slowing the current cycle of spread will be difficult. But encouraging Americans to wear higher-quality masks is a simple step that might make a difference.
J. Projections & Our (Possible) Future
1. Proven Model Shows C19 Cases Could Nearly Double By End of January
The evolution of C19 depends on how much we, as a country, continue to social distance or return back to normal levels of interaction. This chart shows forecasted cases in the U.S. through the end of January 2021 based on our current social distancing levels, as well as less and more social distancing.
20 million infected Americans by late January
- The number of confirmed C19 cases are likely to increase to 20 million by the end of January, nearly doubling the current level of 11.4 million cases, predicts a Washington University in St. Louis C19 forecasting model.
- The model, which accurately forecasted the rate of C19 growth over the summer of 2020, was developed by Olin Business School’s Meng Liu, Raphael Thomadsen and Song Yao. Their paper presenting the model and its forecasts was published November 23, 2020, by Scientific Reports.
- “One of the key reasons for the increased accuracy of this model over other C19 forecasts is that this model accounts for the fact that people live in interconnected social networks rather than interacting mostly with random groups of strangers,” said Thomadsen, professor of marketing. “This allows the model to forecast that growth will not continue at exponential rates for long periods of time, as classic C19 forecasts predict.”
- An interactive online version of the model also allows users to observe the impact different levels of social distancing will have on the spread of C19. The current social distancing reflects an approximate 60% return to normalcy, as compared with the level of social distancing before the pandemic. If we continue, as a nation, at the current level of social distancing, the model forecasts that we are likely to reach 20 million cases before the end of January 2021.
- “Even small increases in social distancing can have a large effect on the number of cases we observe in the next two and a half months,” Thomadsen said. “Going back to a 50% return to normalcy, which was the average level of distancing in early August, would likely result in 5 million fewer cases by the end of January.
- “We could effectively squash out the COVID growth within a few weeks if we went back to the levels of social distancing we experienced in April.”
- However, the researchers caution that this is likely a conservative estimate due to increased testing and the upcoming holidays.
- “In our model, we assume that only 10% of cases are ever diagnosed, meaning that we will start to hit saturation,” said Song Yao, associate professor of marketing and study co-author. “However, more recently, testing has increased, and probably more like 25% of cases are diagnosed. In that case, total COVID cases would increase beyond 20 million in the next few months unless we, as a society, engage in more social distancing.”
- “The upcoming holiday seasons will present a great deal of uncertainty to the outlook of the pandemic as people travel more at the end of the year. This will likely make our forecast an optimistic one,” said Meng Liu, assistant professor of marketing and study co-author.
2. Coronavirus Will Become Seasonal
- As the global coronavirus pandemic continues, scientists are not only trying to find vaccines and drugs to combat it, but also to continuously learn more about the virus itself. “By now we can expect the coronavirus to become seasonal,” explains Ralf Bartenschlager, professor in the Department of Infectious Diseases, Molecular Virology, at Heidelberg University. “Thus, there is an urgent need to develop and implement both prophylactic and therapeutic strategies against this virus.” In a new study, Bartenschlager, assisted by the Schwab team at EMBL Heidelberg and using EMBL’s Electron Microscopy Core Facility, performed a detailed imaging analysis to determine how the virus reprograms infected cells.
- Cells that become infected by the coronavirus (SARS-CoV-2) die rather quickly, within only 24 to 48 hours. This indicates that the virus harms the human cell in such a way that it is rewired and essentially forced to produce viral progeny.
- The main aim of the project was therefore to identify the morphological changes within a cell that are inherent to this reprogramming. “To develop drugs which suppress the viral replication and thereby the consequence of the infection, as well as the virus-induced cell death, is key to have a better understanding of the biological mechanisms driving the virus’ replication cycle,” explains Bartenschlager. The team used the imaging facilities at EMBL and state-of-the art imaging techniques to determine the 3D architecture of SARS-CoV-2-infected cells, as well as alterations of cellular architecture caused by the virus.
- The team was able to create 3D reconstructions of whole cells and their subcellular compartments. “We are providing critical insights into virus-induced structural changes in the studied human cells,” explains Ralf Bartenschlager. The images revealed an obvious and massive change in the endomembrane systems of the infected cells – a system that enables the cell to define different compartments and sites. The virus induces membrane changes in such a way that it can produce its own replication organelles.
- These are mini replication compartments where the viral genome is amplified enormously. To do this, the virus requires membrane surfaces. These are created by exploiting a cellular membrane system and creating an organelle, which has a very distinct appearance. The scientists describe it as a massive accumulation of bubbles: two membrane layers forming a big balloon. Within these balloons – which form a very shielded compartment – the viral genomes are multiplied and released to become incorporated into new virus particles.
- This striking change can be seen in the cells only a few hours after infection. “We saw how and where the virus replicates within the cell, and how it hijacks its host machinery to be released after multiplication,” Schwab says. Until now, little was known about the origin and development of the effects that SARS-CoV-2 causes in the human body. This includes a lack of knowledge about the mechanism by which the infection leads to the death of infected cells. Having this information now will foster the development of therapies reducing virus replication and, thus, disease severity.
A portion of an infected cell is observed by transmission electron microscopy, in which SARS-CoV-2-specific structures (in red, from the mirrored image on the right) can be detected as early as six hours after infection. The virus’s genome is replicated in high copy number in two membrane layers forming a big balloon (large structures in red), which forms a very shielded compartment. New virions (small structures in red) are being formed by budding at the interface of the endoplasmic reticulum and Golgi apparatus.
- The team has made sure that the collected information and, in particular, the unprecedented repository of 3D structural information about virus-induced substructures can be used by everyone. “
K. Practical Tips & Other Useful Information
1. Answers to Every Possible Pandemic-Thanksgiving Question
- Most years, in the anxious days before Thanksgiving, I write a health-related FAQ. It’s meant to be fun, reminding us of the timeless risks that spike every year around this day, such as Salmonella poisoning and fires from exploding turkeys.
- This year is different. On Thursday, the CDC advised Americans not to congregate with people outside their immediate household. If anything, the advisory understated the risk at hand, saying that “travel may increase your chance of getting and spreading C19.” Travel does increase your risk. It should have read: Do not travel. Do not gather. Effectively, Thanksgiving is canceled. Just wait one year, and then have a basically normal holiday. If everyone in the United States did this, we’d likely save thousands of lives.
- Many people have changed or pared down their holiday plans, but many others have purchased tickets, their hearts and minds made up. At this point, since millions of people are likely to attempt some form of intermediate-risk Thanksgiving, we should consider a harm-reduction approach. Just as sex-education classes for teens are not meant to encourage those activities, this FAQ is not an endorsement of Thanksgiving gatherings. It is only an attempt to respond to reality.
If you’re going to travel to see family, how should you rank the modes of transport?
- Purely from the standpoint of coronavirus transmission (not carbon emissions, cost, time, or other safety concerns), here’s a very rough hierarchy from safest to riskiest:
Does the risk of air travel change during Thanksgiving if tons of people fly?
- Yes. Up until now, flying itself has proved to be low risk: The ventilation is good, and people wear masks and are mostly quiet. Airports with large crowds are likely more hazardous than time spent on the plane, and that risk will increase as more people travel. Still, the act of flying in a plane is less of an issue than close, prolonged contact in a home where people are eating and socializing. Traveling vigilantly, only to arrive at someone’s home and act as though there is no pandemic, is a serious misallocation of anxiety.
I’m not feeling well, but I think it’s just a cold, because I tested negative for the virus. Should I go to an outdoor gathering?
- No. A negative test isn’t enough to reassure you that you don’t have the virus, especially if you have symptoms. The most common coronavirus test, a PCR test, can confirm only that you do have the virus, but it can’t ensure that you definitely don’t.
If you’re not feeling sick, is it morally defensible to get a coronavirus test in order to see family, given testing shortages?
- In many cases, no. Sick people need those tests, and so do essential workers. They don’t need to be waiting in a three-hour-long line between shifts to get tested. That said, there are situations in which people may have an urgent need to see one another this winter. The most obvious example is when someone is terminally ill or unable to care for themselves, or they are especially isolated and depressed. If you’re fortunate to not fall in any of those categories, and seeing family can wait until the spring or summer, do that. Leave the tests for those who need them.
Should my family do temperature checks at the door?
- No. This is an even less effective mode of screening than PCR tests. By the time a fever develops—if it does at all—you’ve likely been contagious for days. So temperature checks give a false sense of security. The fact that someone doesn’t have a fever isn’t meaningful information that should change how they behave, or how anyone else behaves around them.
How much safer is an outdoor meal than an indoor meal?
- Much, much safer. Almost all transmission of this virus happens indoors.
Even if people are close together?
- Eating outdoors doesn’t mean you’re invincible. Still try to stay six feet apart. If you huddle together around a cramped table and have close, face-to-face conversations with the people next to you, you could absolutely infect them.
What if Uncle Al won’t pull his mask up over his nose?
- If you insist on having a family gathering, at least make clear ground rules. Ask everyone to agree to them beforehand, and to help correct people who seem to be forgetting. Even if Uncle Al believes some bizarre chain email he read about how masks are communist propaganda, he agreed to the rules for the day. Once he has made the choice to attend, he has made the choice to wear a mask, and to wear it properly. If he doesn’t go along with the rules, the whole group should ask him to leave.
Why is everyone freaking out? I’ve gotten together with my family several times since the start of the pandemic and no one has gotten sick. Most cases of C19 are mild.
- I think that’s exactly the challenge. Warning people about this virus isn’t like warning them not to touch a hot stove. In that case, the outcome is predictable every single time. With C19, a Thanksgiving dinner may leave everyone unscathed—or it may lead to serious illness and death for multiple people around the table, and countless more who contract the virus from them. But, taken together, it’s practically inevitable that lots of individual “it’s probably fine” choices accumulate into one enormous, very bad decision.
- Anthony Fauci said this weekend that we all need to do a “risk-benefit assessment” before traveling. I think the benefit of Thanksgiving is so great that I’m willing to take the risk.
- Assessing the risk of any single gathering is impossible. Even if you’re ready to die, and you’d sooner die than do a virtual Thanksgiving, you could infect other people and set off a chain of infections. Any assessment of personal risk that you’re willing to take would have to factor in how much harm you’re willing to cause.
My 95-year-old mother is staying with my sister in Vermont, and my wife and I were planning to drive and see them for Thanksgiving. Both my wife and I have had very little contact with other people. We practice social distancing, and dinner will be no different. Can this be done safely?
- Nothing is perfectly safe. But your number of merged bubbles is only two, and they are small bubbles. And the fact that your mother is 95 is significant. If it’s very important for her to see you on the holiday, and she understands her particularly high risk, the time with her may be justifiable. If you all decide to do this, remember that just as you’ve been careful before this dinner, your family should be equally or more vigilant for two weeks after.
I’m alone this Thanksgiving. What should I do?
- Lots of people are alone for Thanksgiving every year. Fortunately, this year has produced tons of guides for cooking for one. There are also new ways to interact with family and friends that didn’t exist in the past. Suddenly, eating in front of your computer has gone from sad to virtuous, and potentially even fun.
Since coronavirus cases are rising in some places more than others, should people evaluate their Thanksgiving risk differently depending on where they live?
- Technically, risk increases as the disease becomes more ubiquitous. That is, a 20-person gathering in a part of the world with little or no virus, such as New Zealand, is very unlikely to lead to infections. The same 20-person gathering in the U.S. is more likely to lead to infections. And at a practical level, though, no part is free of the virus to a degree that should allow people to gather outside their bubbles without extreme precautions.
Because some hospitals are overloaded, should we stop doing things that are unrelated to the pandemic? Like shoveling snow? Speeding? Opening a champagne bottle with a sword?
- The sword openings are fine. But never speed. Keep a regular exercise routine to lower the chance of having a heart attack when you shovel snow. This winter is going to be a bad one to find yourself in a hospital. If you’re seriously injured, you’ll likely get medical care that’s similar to what you would receive in another year. But minor injuries and mild symptoms of conditions such as heart disease will be triaged, delayed, and missed. The health effects will play out in years to come. Those who do get treated in a hospital will add to the strain on an already overwhelmed health-care system. About one in five American hospitals is already short on staff, and hospitalizations continue to rise. There are some regional variations to this answer, but overall this is not a good time to need elective care. Be especially careful.
- I feel restless. I can’t just sit at home and do nothing. I’m worried about everyone having Thanksgiving. I’m not a medical professional, but I want to help.
- The U.S. is seeing a surge in food insecurity. If you can volunteer any time, money, or nonperishable foods, now is a great time to do that. You don’t need a medical degree to help address the effects of the pandemic. A sense of purpose can go a long way to staving off the darkness of winter in any year, but especially this one.
If I put a frozen turkey into a deep fryer this year, will it still explode?
- Yes, thaw your turkey. Dropping a frozen turkey into boiling grease will send flames 20 feet into the air. Yet people do it every year. There are some truths about humanity that even a pandemic cannot change.
2. C19 Researchers Identify Features of a Super-Spreader
- New research from the University of Central Florida has identified physiological features that could make people super-spreaders of viruses such as C19.
- In a study appearing this month in the journal Physics of Fluids, researchers in UCF’s Department of Mechanical and Aerospace Engineering used computer-generated models to numerically simulate sneezes in different types of people and determine associations between people’s physiological features and how far their sneeze droplets travel and linger in the air.
- They found that people’s features, like a stopped-up nose or a full set of teeth, could increase their potential to spread viruses by affecting how far droplets travel when they sneeze.
- According to the CDC, the main way people are infected by the virus that causes C19 is through exposure to respiratory droplets, such as from sneezes and coughs that are carrying infectious virus.
- Knowing more about factors affecting how far these droplets travel can inform efforts to control their spread, says Michael Kinzel, an assistant professor with UCF’s Department of Mechanical Engineering and study co-author.
- “This is the first study that aims to understand the underlying ‘why’ of how far sneezes travel,” Kinzel says. “We show that the human body has influencers, such as a complex duct system associated with the nasal flow that actually disrupts the jet from your mouth and prevents it from dispersing droplets far distances.”
- For instance, when people have a clear nose, such as from blowing it into a tissue, the speed and distance sneeze droplets travel decrease, according to the study.
- This is because a clear nose provides a path in addition to the mouth for the sneeze to exit. But when people’s noses are congested, the area that the sneeze can exit is restricted, thus causing sneeze droplets expelled from the mouth to increase in velocity.
- Similarly, teeth also restrict the sneeze’s exit area and cause droplets to increase in velocity.
- “Teeth create a narrowing effect in the jet that makes it stronger and more turbulent,” Kinzel says. “They actually appear to drive transmission. So, if you see someone without teeth, you can actually expect a weaker jet from the sneeze from them.”
- To perform the study, the researchers used 3D modeling and numerical simulations to recreate four mouth and nose types: a person with teeth and a clear nose; a person with no teeth and a clear nose; a person with no teeth and a congested nose; and a person with teeth and a congested nose.
- When they simulated sneezes in the different models, they found that the spray distance of droplets expelled when a person has a congested nose and a full set of teeth is about 60 percent greater than when they do not.
- The results indicate that when someone keeps their nose clear, such as by blowing it into a tissue, that they could be reducing the distance their germs travel.
- The researchers also simulated three types of saliva: thin, medium, and thick.
- They found that thinner saliva resulted in sneezes comprised of smaller droplets, which created a spray and stayed in the air longer than medium and thick saliva.
- For instance, three seconds after a sneeze, when thick saliva was reaching the ground and thus diminishing its threat, the thinner saliva was still floating in the air as a potential disease transmitter.
- The work ties back to the researchers’ project to create a C19 cough drop that would give people thicker saliva to reduce the distance droplets from a sneeze or cough would travel, and thus decrease disease-transmission likelihood.
- The findings yield novel insight into variability of exposure distance and indicate how physiological factors affect transmissibility rates, says Kareem Ahmed, an associate professor in UCF’s Department of Mechanical and Aerospace Engineering and study co-author.
- “The results show exposure levels are highly dependent on the fluid dynamics that can vary depending on several human features,” Ahmed says. “Such features may be underlying factors driving superspreading events in the C19 pandemic.”
3. Home health care improves C19 outcomes
- Survivors of C19 are a vulnerable population who often have health ramifications from their illness and hospital stay. Upon returning home from acute care, large proportions of survivors experience functional dependencies, pain, dyspnea, and exhaustion. Until now, no data has been available on the outcomes of C19 patients discharged home after hospitalization and their recovery needs.
- In a new study from the University of Pennsylvania School of Nursing (Penn Nursing), rich data from more than 1,400 C19 patients admitted to home health care after hospital discharge describes home visit care and recovery extent. In the study, 94% percent of the patients discharged to home health care, which included skilled nursing and physical therapy, achieved statistically significant improvements in symptom burden and functional outcomes and 87% had no adverse events. The study indicates that increasing referrals to home health care has the potential to provide support and achieve improved recovery for these patients.
- “Our findings suggest that acute care providers might carefully consider which C19 survivors would benefit from home health care after hospitalization,” writes Kathryn H. Bowles, PhD, RN, FAAN, FACMI, Professor of Nursing and van Ameringen Chair in Nursing Excellence at Penn Nursing. “A decision support tool to identify general hospitalized patients for home health care referral may be helpful.” Bowles was the lead investigator of the study.
4. CDC Finalizing Recommendation to Shorten C19 Quarantines
- The U.S. Centers for Disease Control and Prevention may soon shorten the length of time it recommends that a person self-quarantine after potential exposure to the coronavirus, hoping that such a step will encourage more people to comply, a top agency official said.
- CDC officials are finalizing recommendations for a new quarantine period that would likely be between seven and 10 days and include a test to ensure a person is negative for C19, said Henry Walke, the agency’s incident manager for C19 response.
- Agency officials are discussing the exact time period and what type of test a person would be given to exit quarantine, he said.
- “We do think that the work that we’ve done, and some of the studies we have and the modeling data that we have, shows that we can with testing shorten quarantines,” he said.
- If a test comes back negative, he added, “then their probability of going on and developing an infection after that is pretty low.”
- There is a risk that some infections would be missed, Dr. Walke said, but it may be worth the potential trade-off. “Hopefully, people would be better able to adhere to quarantine if it was, for example, seven to 10 days,” he said.
- Health authorities have recommended a 14-day quarantine, along with other precautions like wearing masks and keeping a distance, to curb transmission of the virus. The quarantine length is based on the time researchers believe it takes for infection to lead to symptoms.
- Yet some public-health experts say 14 days is too long in certain cases, citing evidence about how long someone is infectious combined with the latest strategies for testing for the virus. Moreover, they say, people are weary after months of restrictions.
- A huge surge in new infections in the U.S.—fueled in part by that same pandemic fatigue—is sending thousands into lengthy quarantines and increasing the burden on public-health agencies to track these people, as well as on companies confronting large numbers of employees out due to 14-day quarantines.
- How a quarantine’s length affects peoples’ willingness to comply, however, hasn’t been well studied, the public-health experts say. In addition, getting a test to end a quarantine could be difficult for people in places where demand for tests is rising.
- About 50% of people who become ill develop symptoms between five and six days after they are infected, while 9% develop symptoms after 10 days, and 2% after 14 days, said Justin Lessler, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, citing estimates he and other researchers have published.
- “If we could get people to quarantine—and really quarantine, like you can’t go to the grocery store when you quarantine—then I think there’s an argument for shorter times,” he said.
- Quarantine lengths can depend on the situation, Dr. Lessler said. A shorter period ending with a test might be justified before returning to an office with others who are healthy. Yet a full 14 days might be more prudent before visiting an elderly relative.
- A 14-day quarantine period is warranted in countries that have few cases, he said, because one missed case could spark a new outbreak.
- France, Germany and Belgium, experiencing their own surge of infections, have already cut the length of time people who are potentially exposed to C19 need to self-quarantine. The World Health Organization currently recommends a 14-day quarantine, but expert groups that advise it are reviewing the data, a WHO spokeswoman said.
L. Johns Hopkins C19 Update
November 24, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 58.90 million cases and 1.39 million deaths as of 12pm EST on November 24. The WHO reported a new global record for weekly incidence with 4.06 million new cases, a slight increase over the previous week. The WHO also reported 67,225 deaths, an 11% increase over the previous week and another new record high. Additionally, the WHO reported the second highest single-day mortality to date, with 11,863 deaths on November 21.
- The US CDC reported 12.18 million total cases and 255,958 deaths. The US surpassed 12 million cumulative cases on November 21. From the first case reported in the US on January 22, it took 96 days to reach 1 million cases. From there:
- 1 to 2 million- 44 days
- 2 to 3 million- 27 days
- 3 to 4 million- 15 days
- 4 to 5 million- 17 days
- 5 to 6 million- 22 days
- 6 to 7 million- 25 days
- 7 to 8 million- 21 days
- 8 to 9 million- 14 days
- 9 to 10 million- 10 days
- 10 to 11 million- 7 days
- 11 to 12 million- 5 days
- The US reported its 3 highest single-day totals on November 19-21, including a record high of 192,673 new cases on November 20. Additionally, the US is currently averaging more than 170,000 new cases per day, which corresponds to nearly 1.2 million cases each week. The US also reported more than 2,000 deaths on November 19 for the first time since May 14*—and the highest daily total since May 7.* The average daily C19 mortality is now 1,498 deaths per day, the highest since May 14, and it appears to be increasing exponentially.
- The COVID Exit Strategy website now classifies every state except Hawai’i—including Washington, DC—as having Uncontrolled Spread. Testing volume continues to increase in the US, but it is not keeping pace with increasing transmission in the vast majority of states. In total, only 5 states—plus Washington, DC—are reporting test positivity of 5% or less: Hawai’i, Maine, Massachusetts, New York, and Vermont. In contrast, 14 states are reporting 15% or more. Among the most concerning states are Idaho (40.1%), Iowa (43.1%), Kansas (38.2%), South Dakota (44.1%), and Wyoming (68.7%).
- The Johns Hopkins Coronavirus Resource Center testing tracker reports 9 states with test positivity of 30% or higher, including Mississippi at 86.0% and Wyoming at 77.2%. Additionally, both the COVID Exit Strategy and Johns Hopkins Coronavirus Resource Center indicate that the majority of US states are reporting increasing test positivity, another concerning sign as the US approaches the holiday season.
- There is some evidence that states affected early in the ongoing surge are starting to peak in terms of daily incidence. The vast majority of states continue to report increasing trends, but Iowa (-12% over the past 2 weeks), North Dakota (-7%), and South Dakota (-11%) have all reported decreasing daily incidence over the past week or so. The daily incidence in all 3 states remains elevated, but there is an initial indication that they may have passed a peak. The official CDC data illustrate this well. Additionally, Hawai’i continues to demonstrate the ability to contain its C19 epidemic, reporting a 7% decrease in daily incidence over the past 2 weeks.
- Conversely, the C19 epidemics in a number of states continue to accelerate rapidly. Notably, the daily incidence has doubled or more over the past 2 weeks in Louisiana (+190%), New Hampshire (+105%), New Mexico (+125%), and Vermont (+214%). Another 19 states have reported increases of more than 50% over the past 2 weeks.
- Iowa and North and South Dakota were among the states affected earliest in the current surge, so it would not be surprising if these states peaked earlier than others. With that in mind, reporting is likely to be delayed and erratic, to some degree, over the Thanksgiving holiday weekend, and increased travel as students return home from colleges and universities and individuals and families travel for Thanksgiving will likely factor into transmission and testing volume. It might be a little difficult to monitor epidemiological trends over the coming weeks.
- The Johns Hopkins CSSE dashboard reported 12.45 million US cases and 258,364 deaths as of 12:30pm EST on November 24.
2. ASTRAZENECA VACCINE
- AstraZeneca issued a press release regarding preliminary results from the Phase 3 clinical trials of its candidate SARS-CoV-2 vaccine, developed in collaboration with Oxford University (UK). The press release indicates that the vaccine demonstrated 90% efficacy when administered as an initial half-dose followed by a full dose a month later. Interestingly, however, the vaccine was 62% efficacious in participants who received 2 full doses over the same period of time, resulting in an overall efficacy of 70%. No serious adverse events were identified in the trials.
- In total, the Phase 3 portion of the trials included more than 11,000 participants, and the researchers identified 131 C19 cases. As has been the case throughout the pandemic, the data published via press release have not yet been peer reviewed, although the researchers reportedly intend to publish the full data in the near future.
- The increased efficacy among participants who received the initial half-dose has sparked interest among experts. This analysis was based on only 2,741 participants who appear to have received the smaller dose unintentionally, according to a statement by AstraZeneca. The mechanism by which the smaller first dose resulted in higher efficacy is unclear, but representatives from AstraZeneca indicate that this dosing regimen will be investigated further to better characterize its effects.
- One theory is that the smaller initial dose is not enough to stimulate a full immune response, which could reduce the likelihood that the immune system would suppress the second “booster” dose. At 70% efficacy, the AstraZeneca vaccine could face challenges in terms of regulatory approval, as there are already 2 vaccines with reported efficacy in excess of 90%; however, if the half-dose regimen is, in fact, more efficacious, it could provide a third option.
- The AstraZeneca vaccine can be stored at normal refrigeration temperatures for up to 6 months. AstraZeneca has already committed to providing more doses globally than any other manufacturer by a factor of 2 over the nearest manufacturer (Novavax)—including for low-and-middle-income countries and the WHO COVAX Facility.
3. VACCINE EUA REVIEW
- The US FDA announced that its Vaccines and Related Biological Products Advisory Committee will convene on December 10 to review the Emergency Use Authorization (EUA) requests submitted by Pfizer and BioNTech for their candidate SARS-CoV-2 vaccine. FDA Commissioner Dr. Stephen Hahn emphasized that while the advisory board “will review the request as expeditiously as possible,” it is unclear how long the review process will take. That being said, this represents another major step toward authorization for a SARS-CoV-2 vaccine. The FDA intends to livestream the meeting via its YouTube, Facebook, and Twitter accounts as well as from the FDA website.
- In last week’s press release announcing that Pfizer and BioNTech submitted the EUA request, the companies commented that they would be ready to begin distributing the first doses of the vaccine “within hours after authorization.” Dr. Moncef Slaoui, Operation Warp Speed’s chief scientific advisor, reportedly expects the FDA to grant the first vaccine EUA in mid-December, and in an interview with Wired, US NIH Director Dr. Francis Collins said that he expects the US to be able to fully vaccinate (ie, both doses) 20 million people by the end of December.
4. RUSSIA VACCINE
- Russia announced another round of preliminary results from clinical trials of its Sputnik V SARS-CoV-2 vaccine. The interim analysis indicates that the vaccine is 91.4% efficacious at 28 days after the first dose and 95% efficacious after 42 days. The analysis includes data from nearly 19,000 participants, and the researchers identified 39 C19 cases. Efficacy at this level would put the Russian vaccine on par with the 3 other vaccines with recently reported Phase 3 clinical trial data.
- No serious adverse events were reported. Like other recently reported vaccine trial data, these results have not yet been peer reviewed, but researchers from Russia’s Gamaleya Center intend to publish their analysis in a peer-reviewed journal. In total, 40,000 individuals are participating in the ongoing Phase 3 clinical trials. Coinciding with the announcement, Russian President Vladimir Putin announced at the G20 Summit that Russia is ready to make the vaccine available to other countries. In addition to Sputnik V, Russia is currently developing and testing at least 2 other vaccines.
5. MONOCLONAL ANTIBODY TREATMENT EUA
- The US FDA issued an Emergency Use Authorization (EUA) for another monoclonal antibody treatment for C19. The newest EUA is for a combination therapy using casirivimab and imdevimab, developed by Regeneron Pharmaceuticals, which are monoclonal antibodies that target the receptor binding domain for the SARS-CoV-2 spike protein. Similar to the previous FDA EUA for the Eli Lilly monoclonal antibody treatment, this combination is authorized for use in mild or moderate C19 patients (aged 12 years and older) who are not currently hospitalized but who are at high risk of progressing to severe disease. It is not authorized for patients who are currently hospitalized or receiving supplemental oxygen therapy for C19 or an underlying health condition. The 2 products must be administered together.
- Reportedly, US President Donald Trump received the combination therapy when he was diagnosed with C19 in October under a Compassionate Use protocol, as the treatment had no formal authorization from the FDA at that time. Regeneron indicated that it expects to have enough supply to treat 80,000 patients by the end of the month; 200,000 by early January 2021; and 300,000 by the end of January. Additionally, Regeneron is partnering with Roche Pharmaceuticals to increase production capacity in early 2021.
6. MASKS & ASYMPTOMATIC TRANSMISSION
- In a recent scientific brief, the US CDC examined the community use of cloth masks to mitigate SARS-CoV-2 transmission risk. Cloth masks protect the community both by limiting potentially infectious droplets exhaled by the wearer and by filtering droplets from air inhaled by the wearer. The CDC also stated that mask use is particularly important considering that asymptomatic or presymptomatic individuals are responsible for more than 50% of all transmission.
- A recent study conducted in Kansas found that counties that imposed a mask mandate exhibited a decrease in transmission, while counties that did not experienced an increase. The counties with mask mandates reported a 6% decrease in daily incidence, while without a mandate reported a 100% increase over the same period. The study findings are consistent with similar studies conducted in other states that did and did not have mask mandates.
7. AIR TRAVEL
- The US is staring down its busiest air travel period since March, in preparation for the annual US Thanksgiving holiday, with volume exceeding 1 million passengers on November 20 and 22. While the US CDC continues to strongly recommend that individuals refrain travel and large gatherings, it has updated guidance to recommend that prospective international travelers get tested before leaving and after returning.
- Additionally, the CDC recommends quarantining for at least 7 days after travel, regardless of the test results—and 14 days for those who do not get tested after returning. Furthermore, the guidance recommends that individuals delay or cancel travel plans if they test positive or do not receive the results of their testing prior to travel.
8. HOSPITAL SHORTAGES
- As the US continues to battle its largest C19 surge since the onset of the pandemic, many hospitals across the country are reaching capacity. Bed availability, ventilators, and hospital staff are all limiting factors that could affect hospital surge capacity as more patients are admitted. According to data released this week by the US Department of Health and Human Services (HHS), more than 1,000 hospitals are “critically” short staffed. In North Dakota, a major US hotspot, more than half of all hospitals are reporting critical staffing issues.
- Considering the largely rural population of many states currently experiencing C19 surges, small community hospitals can become overwhelmed more quickly than their urban counterparts. Many rural hospitals in Kansas and Missouri have been sending their most critically ill patients to urban, flagship hospitals for care; however, this constant stream of critically ill patients is reportedly starting to overwhelm these larger, better-equipped facilities as well.
- According to one hospital in Kansas City, Missouri, nearly 25% of C19 patients came from outside of the city. While ventilators and other intensive care equipment must be carefully maintained, many rural providers also report that they are again running low on critical PPE. Some hospitals are rationing gowns, gloves, and N95 respirators in order to extend existing inventory and supply. With these resource constraints, some hospitals are investing in expensive UV-light disinfecting equipment in order to reuse N95 respirators. But with cases still continuing to rise across the US ahead of the holiday season, it is unclear how long hospitals can withstand the added strain before moving to a crisis-standards-of-care approach.
9. GAZA STRIP
- Crowding in Gaza, Palestine, is contributing to a dramatic rise in C19 incidence that officials warn could lead to the collapse of the healthcare system, potentially within days. This strain is further complicated by low existing supplies of testing kits, PPE, ventilators, hygiene supplies, drugs, and oxygen-generating machines. Multiple news media reports indicate that the long-standing blockade by Israel and Egypt may also be contributing to supply limitations.
- One report by Al Jazeera indicates that many in the public have resisted recommendations to wear masks and practice appropriate social and physical distancing, and many continue to participate in large gatherings, which likely contributes to increased transmission. Some senior health officials have advocated for a 2-week lockdown to bring transmission under control, but no new measures have been announced.
10. CLINICAL COURSE
- Researchers from US CDC published an article in JAMA that proposes a framework and timeline for the clinical course of disease for C19 patients. The authors break down the disease into 3 phases:  an acute phase during the first 2 weeks after symptom onset, characterized by the common acute C19 symptoms (eg, fever, respiratory symptoms);  a less-common post-acute hyperinflammatory illness, such as the multi-system inflammatory syndrome in children and adults (MIS-C and MIS-A) that can occur between weeks 2 and 4 after symptom onset; and  a later phase of longer-term sequelae, commonly referred to as “long hauler” symptoms, which can occur 1 month or later after symptom onset. The authors explicitly note that patients may not experience all phases, and it is not necessary to experience earlier phases in order to progress to later phases.
- STAT News reported that the survival rate among hospitalized patients has increased over the course of the pandemic, due to better clinical management by healthcare providers who have gained a greater understanding of the disease. Additionally, treatment options, including newly authorized drugs (eg, under EUAs), provide a wider range of therapies beyond supplemental oxygen and supportive care. In spite of this progress, increasing transmission, particularly leading into the winter season and holidays, could lead to hospitals being overwhelmed with a wave of new patients requiring hospitalization, which could limit the care available to C19 patients and negatively impact patient treatment and survival.
11. US CDC C19 TRAVEL ADVISORIES
- The US CDC published a major update to its C19 travel guidance, including adding a new Alert Level. Previously, CDC travel advisories went through Level 3 (Avoid Nonessential Travel), but in the most recent update, the CDC added a Level 4 travel advisory to its C19-specific travel guidance. Level 4 corresponds to “Very high level of C19,” defined as more than 100 per 100,000 population over the past 28 days for countries with populations greater than 200,000 and more than 100 total cases over the past 28 days for smaller countries.
- The CDC will also consider secondary data, including hospitalization rates, test positivity, and the rate of change in C19 incidence. The CDC recommends “avoid[ing] all travel” to countries in the Level 4 tier. The CDC moved 179 countries and territories to Level 4, and there remain 59 total countries in Levels 1 (take C19 precautions) and 2 (avoid all nonessential travel), although there are currently no countries in Level 3 (also avoid nonessential travel). The CDC also recommends avoiding travel to 9 territories due to a lack of C19 reporting and unknown C19 status. Notably, the new Level 4 appears to only apply to C19, as the rest of the CDC’s travel guidance only lists 3 levels.
- The US Department of State travel advisories utilize a Level 4 (Do Not Travel), which has caused some confusion during the C19 pandemic. Notably, the State Department issued a global Level 4 travel advisory from March to August due to pandemic, and it has issued C19-related Level 4 advisories for many individual countries since then. Prior to the CDC update, the CDC did not utilize an “avoid all travel” travel advisory, so there were discrepancies between the two sets of travel guidance—ie, avoid nonessential travel under the CDC travel guidance vs do not travel under the State Department travel guidance. Now, the situation has reversed, with the CDC recommending that individuals “avoid all travel” to nearly 200 countries and territories, while the State Department has C19-related Level 4 travel advisories for only 25 countries.
- In addition to specific countries and territories, the CDC also updated cruise ships worldwide to a Level 4 travel advisory. In late October, the CDC lifted its “no sail” order and issued guidance for cruise lines to begin resuming operations in US territorial waters; however, it appears that the CDC has changed course following the report of an outbreak on the first cruise ship to resume operations in the Caribbean Sea. Like the updated countries and territories, the CDC previously listed cruise ships as a Level 3 travel advisory, although it is unclear what would have constituted essential travel on a cruise ship.
12. CRISIS STANDARDS OF CARE
- The Johns Hopkins Center for Health Security published a report on lessons from New York City hospitals’ use of crisis standards of care (CSC) during the unprecedented surge of C19 patients in April-June. Many hospitals were overwhelmed and found it necessary to adjust the way in which care was provided in order to focus on providing the greatest overall benefit for C19 patients. The researchers convened a working group consisting of 15 NYC hospital intensive care unit (ICU) directors to discuss challenges and lessons regarding CSC to support hospital systems nationwide as they adapt to the ongoing C19 epidemic.
- The working group identified a number of key takeaways and areas for further investigation. Notably, pre-pandemic planning for CSC did not necessarily apply well to C19 environment, and existing plans needed to be adapted in the midst of the surge to account for C19-specific operational realities and clinical needs. The working group members also discussed the importance of inter-hospital collaboration in order to maintain flexible capacity and adapt to dynamic patient surge conditions, and they noted that many clinicians struggled to maintain situational awareness, especially regarding patient load and resource availability.
- Real-time decision-making regarding patient triage or allocation of limited healthcare personnel or other resources was a major challenge, and healthcare workers experienced mental health and psychological effects due to implementing CSC. Additional research is needed to better operationalize CSC decision-making policies, and CSC plans need to include specific triggers and formal declarations that address the scope of the CSC, including the specific processes and resources to which they apply. Additionally, rapid decision-making processes need to be established to reduce delays in allocating personnel and resources that could endanger patients’ health. One of the biggest limitations during the C19 surge was not equipment, but rather, personnel, which will likely remain a major limitation throughout the US C19 epidemic.
13. SANTA CLAUS & MENSCH ON A BENCH
- As the US CDC and other health experts continue to emphasize the importance of social and physical distancing to mitigate SARS-CoV-2 transmission risk, children around the world can rest easy over the upcoming holiday season. Dr. Anthony Fauci recently confirmed that Santa Claus is immune to SARS-CoV-2 infection, due the strength of his “innate immunity.”
- Santa may not be making his usual holiday appearances in many stores and shopping malls this year, to reduce the risk of children and families spreading the infection in holiday shopping crowds, but he is keeping his traditional schedule to deliver presents around the world on Christmas Eve. Dr. Fauci noted that St. Nick will not pose any C19 risk as he makes his annual journey.
- Similarly, Neal Hoffman confirmed that Moshe, the Mensch on a Bench, is also immune. Mr. Hoffman created Mensch on a Bench for his son in 2011 as the Jewish counterpart to Elf on a Shelf. Moshe and Kris Kringle are encouraging individuals and families around the world to take the appropriate precautions to protect against C19 over the holidays.