August 30, 2020
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
4. Mortality Rates
J. Links to Other Stories
LSU Health study explains multipronged coronavirus attack and widespread C19 infection A study of a gateway receptor for coronavirus may help explain the wide variety of symptoms and organs involved with coronavirus infection and C19. The results suggest that a multi-organ infection with coronavirus may be via the angiotensin-converting enzyme 2 receptor, which is found almost everywhere throughout the body.
Mouse-adapted coronavirus model provides new tool for C19 discoveries Mouse model shows success in accelerating development of C19 therapeutics and vaccines.
Single-use N95 respirators can be decontaminated and used again, study finds Scientists hope new methods can mitigate the chronic shortage of personal protective equipment
Beating HIV and C19 may depend on tweaking vaccine molecules In a new Immunity study, researchers at La Jolla Institute for Immunology (LJI) show that one way to improve the body’s immune response to vaccines is to factor in antigen valency.
C19 less deadly and causes milder symptoms in children Children and teenagers are less likely than adults to develop severe C19 or die from the disease, according to the world’s largest study of hospital patients with C19.
MHC class II transactivator CIITA induces cell resistance to Ebola Virus and SARS-like coronaviruses Discoveries from the Benaroya Research Institute at Virginia Mason (BRI) have identified a new cellular protection pathway that targets a common vulnerability in several different pandemic viruses, and collaborators at Case Western Reserve University, Boston University School of Medicine and MRIGlobal have shown that this pathway can protect cells from infection by Ebola virus and coronaviruses, like SARS-CoV-2. Published today in Science, these new findings provide a better understanding of cellular mechanisms involved in viral resistance that can inform future treatments and therapies for viral infectious diseases.
Genetics could impact C19 treatments Over the past few months, a number of drugs have been under investigation to treat C19 without well-established safety or data to support these claims. However, some of these unproven therapies may have underlying genetic reasons for not being effective and resulting in fatal adverse effects as found with hydroxychloroquine.
Scientists establish first lethal mouse model for C19 Army scientists have developed the first lethal mouse model of the coronavirus using mice that were genetically engineered to express the human ACE2 gene–a key mechanism by which the virus enters human cells. In addition to shedding light on the pathogenesis of C19, this work directly contributes to the advancement of medical countermeasures against the virus.
How to Smize (Smile With Your Eyes) When You’re Wearing a Mask Service employees in the Covid era practice a modeling move coined by Tyra Banks to show customers a happy face.
Routine cleaning and disinfecting leaves no trace of coronavirus on surfaces in hospital A new study testing multiple surfaces of a New Jersey oncology unit found no traces of the coronavirus, suggesting that strict cleaning and disinfecting protocols helped limit the virus’ spread. The samples were collected over multiple days before scheduled cleaning of the facility during the height of the New Jersey’s outbreak. The results should help reassure people who need to visit a doctor for a necessary procedure or checkup and may be afraid of the environment, said Dr. Bruce Haffty, a senior author of the study.
C19 is Making College Students Question the Price of Their Education Remote learning, canceled clubs and limited access to on-campus amenities are generating debate about the cost and value of higher education
Does a face mask protect me, or just the people around me? Does a face mask protect me, or just the people around me? It likely provides protection for both. Studies on the new coronavirus and other germs show wearing a mask helps stop infected people from spreading disease to others. Evidence also suggests that masks may offer some protection for the people wearing them.
How four summer camps in Maine prevented C19 outbreaks Measures to limit the spread of the coronavirus, like wearing masks, grouping kids together in cohorts and social distancing, helped protect more than 1,000 kids and staff members at summer camps in Maine from getting infected.
A. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the prior day. Green highlights indicate a decrease or no change and yellow highlights indicate an increase.
1. Cases & Tests (8/29)
- Total Cases = 25,157,450 (+1.0%)
- New Cases = 257,855 (-27,043) (-9.5%)
- New Cases (7 day average) = 251,684 (-1,154) (-0.5%)
- 7 day average of new cases has been relatively stable since 8/24, averaging around 251,000 per day (+/- 2,000)
- 1,000,000+ new cases every 4 days (based on 7 day average)
- Confirmed cases represent approximately 0.33% of world population (estimated number of infections are less than 5% of world population)
US Cases & Testing:
- Total Cases = 6,139,078 (+0.7%)
- New Cases = 42,843 (-6,758) (-13.6%)
- Percentage of New Global Cases = 16.6%
- New Cases (7 day average) = 42,521 (-142) (-0.3%)
- Total Number of Tests = 81,102,397
- Percentage of positive tests (7 day average) = 5.8%
- 7 day average of new cases has been declining since 7/25, but the rate of decline has slowed significantly since 8/22
- 7 day average of new cases has declined 26,809 cases per day since 7/25, a decrease of 38.7%
- 7 day average of percentage of positive tests continues to decline
- Total Deaths = 845,979 (0.6%)
- New Deaths = 5,302 (-409) (-7.2%)
- New Deaths (7 day average) = 5,443 (-11) (-0.2%)
- 7 day average of new deaths have been gradually trending lower since 8/14
- 7 day average of new deaths declined from 5,891 on 8/13 to 5,443 on 8/29, a decrease of 7.6%
- Total Deaths = 186,855 (+0.5%)
- New Deaths = 954 (-151)
- Percentage of Global New Deaths = 18%
- New Deaths (7 day average) = 960 (-3) (-0.3%)
- 7 day average of new deaths have gradually been declining since 8/17
- 7 day average of new deaths have increased from 1,084 on 8/17 to 960 on 8/29, a decrease of 11.4%
3. Top 5 States in Cases, Deaths, Hospitalizations, and Positivity (8/29)
- Coronavirus cases in the Midwest (and Plains) are increasing following warnings from top U.S. health officials.
- Coronavirus cases were growing by 5% or more, based on a weekly average, in 21 states as of Saturday, according to a CNBC analysis of data collected by Johns Hopkins University.
- Several Midwestern & Plains states were among those reporting growing cases (based on 7-day averages) over the last two weeks — Indiana, Iowa, Kansas, Minnesota, North Dakota, and South Dakota.
|State||Cases (8/15)||Cases (8/29)||% Change|
Cases based on 7-day average
- Sun Belt states that have spent the summer months grappling with outbreaks are showing signs of improvement. Texas, Florida, California and Arizona all reported declines greater than 15% compared with a week ago.
4. Mortality Rates
- The average global mortality has decreased from a peak of more than 6,300 new deaths per day on August 14 to 5,425 deaths per day as of August 26. If the global average remains greater than 5,000 deaths per day, the cumulative global mortality could reach 1 million deaths by the end of September.
- Overall, the global daily C19 mortality appears to be starting to decline, following a peak around mid-August. Asia is currently exhibiting the most notable increase in C19 mortality, and South America appears to have reached a plateau.
- Since coming down from its first peak early in the pandemic, Europe has exhibited a very slow increase in mortality, up to 325 deaths per day from a low of 270 in late July. Mortality in Africa and North America peaked in mid-August and has declined steadily since then. Over the past 2 weeks, it appears that most countries are reporting decreasing C19 mortality, an encouraging sign; however, numerous countries reported increases greater than 100% over that period. They are largely distributed around the world, but there is a noticeable concentration in Europe.
- In total, there are 10 countries averaging more than 100 daily deaths. Brazil, India, and the US are all reporting essentially equal daily mortality, approximately 900-950 daily deaths. Mexico is reporting slightly more than half of that total, at 498 daily deaths, and Colombia is reporting 326 daily deaths. The remaining 5 countries are reporting fewer than 250 daily deaths.
- The Central and South America region represents 5 of the top 10 countries in terms of total daily mortality. In terms of per capita daily mortality, 10 countries are averaging 3 or more daily deaths per million population. Of these countries, 8 are from Central or South America. Also in the Americas, the Bahamas is #1 after jumping from just 1 daily death per million population to 10 in only 11 days, and the US falls just outside the top 10 (#12).
Source: Johns Hopkins COVID-19 Update
5. Putting the C19 Death Toll Into Perspective – Here’s the Pandemic’s Impact on US Lifespan
- With over 170,000 C19 deaths to date, and 1,000 more each day, America’s life expectancy may appear to be plummeting. But in estimating the magnitude of the pandemic, UC Berkeley demographers have found that C19 is likely to shorten the average U.S. lifespan in 2020 by only about a year.
- Seeking to put current C19 mortality rates into historic, demographic and economic perspective, UC Berkeley demographers Ronald Lee and Joshua Goldstein calculated the consequences of U.S. lives lost to C19 in 2020 using two scenarios. One was based on a projection of 1 million deaths for the year, the other on the more likely projection of 250,000 deaths.
- Their findings, published online last week in the Proceedings of the National Academy of Sciences journal, conclude that 1 million deaths in 2020 would cut three years off the average U.S. life expectancy, while 250,000 deaths would reduce lifespans by about a year.
- That said, without the societal efforts that have occurred to lessen the impact of C19, there could have been 2 million deaths projected by the end of 2020, a reduction of the average U.S. lifespan by five years, the researchers pointed out.
- Their estimated drop in life expectancy is modest, in part, because 250,000 deaths is not a large increase on top of the 3 million non-C19 deaths expected for 2020, and because older people, who typically have fewer remaining years of life than others do, represent the most C19 fatalities, the study notes.
- Still, while C19 mortality rates remain lower than those of the 1918 Spanish flu pandemic, the coronavirus epidemic could be just as devastating as the longer-lasting HIV and opioid epidemics if mitigation efforts fail, the researchers said.
- “The death toll of C19 is a terrible thing, both for those who lose their lives and for their family, friends, colleagues and all whom their lives touched. Those are real people, not abstract statistics,” said Lee, a UC Berkeley professor emeritus of demography and associate director of the campus’s Center for the Economics and Demography of Aging.
- “But the population perspective helps put this tragedy in a broader context. As we work to contain this epidemic, it is important to know that we have been through such mortality crises before,” he added.
- Goldstein’s and Lee’s measures are based on factors that include a current U.S. population of 330 million, age-specific death rates and the economic valuation of saved lives.
Among their other findings:
- One million C19 deaths in the U.S. in 2020 would be the equivalent of U.S. mortality levels in 1995, adding three years to each American’s biological age, albeit temporarily.
- The age gap (old versus young) for people dying from C19 is marginally wider than during pre-pandemic times, while the male-female gap is slightly narrower. The researchers found similar death-by-age patterns across several countries.
- The economic cost of lives lost to C19 in the U.S. is in the trillions of dollars. According to standard government measures, the demographers estimated that the loss of 1 million lives in 2020 would amount to between $10.2 and $17.5 trillion, while the amount for 250,000 deaths would range from $1.5 to $2.5 trillion.
B. New Scientific Findings & Research
1. The coronavirus is most deadly if you are older and male
- For every 1,000 people infected with the coronavirus who are under the age of 50, almost none will die. For people in their fifties and early sixties, about five will die — more men than women. The risk then climbs steeply as the years accrue. For every 1,000 people in their mid-seventies or older who are infected, around 116 will die. These are the stark statistics obtained by some of the first detailed studies into the mortality risk for C19.
- Trends in coronavirus deaths by age have been clear since early in the pandemic. Research teams looking at the presence of antibodies against coronavirus in people in the general population — in Spain, England, Italy and Geneva in Switzerland — have now quantified that risk, says Marm Kilpatrick, an infectious-disease researcher at the University of California, Santa Cruz.
- “It gives us a much sharper tool when asking what the impact might be on a certain population that has a certain demographic,” says Kilpatrick.
- The studies reveal that age is by far the strongest predictor of an infected person’s risk of dying — a metric known as the infection fatality ratio (IFR), which is the proportion of people infected with the virus, including those who didn’t get tested or show symptoms, who will die as a result..
- “C19 is not just hazardous for elderly people, it is extremely dangerous for people in their mid-fifties, sixties and seventies,” says Andrew Levin, an economist at Dartmouth College in Hanover, New Hampshire, who has estimated that getting C19 is more than 50 times more likely to be fatal for a 60-year-old than is driving a car.
- But “age cannot explain everything”, says Henrik Salje, an infectious-disease epidemiologist at the University of Cambridge, UK. Gender is also a strong risk factor, with men almost twice more likely to die from the coronavirus than women. And differences between countries in the fatality estimates for older age groups suggest that the risk of dying from coronavirus is also linked to underlying health conditions, the capacity of health-care systems, and whether the virus has spread among people living in elderly-care facilities.
Older men more at risk
- To estimate the mortality risk by age, researchers used data from antibody-prevalence studies.
- In June and July, thousands of people across England received a pinprick antibody test in the post. Of the 109,000 randomly selected teenagers and adults who took the test, some 6% harboured antibodies against coronavirus. This result was used to calculate an overall IFR for England of 0.9% — or 9 deaths in every 1,000 cases. The IFR was close to zero for people between the ages of 15 and 44, increasing to 3.1% for 65–74-year-olds and to 11.6% for anyone older. The results of the study have been posted to the medRxiv preprint server.
- Another study from Spain that started in April, and tested for antibodies in more than 61,000 residents in randomly selected households, observed a similar trend. The overall IFR for the population was about 0.8%, but it remained close to zero for people under 50, before rising swiftly to 11.6% for men 80 years old and over; it was 4.6% for women in that age group. The results also revealed that men are more likely to die of the infection than are women — the gap increasing with age.
- “Men face twice the risk of women,” says Beatriz Pérez-Gómez, an epidemiologist at the Carlos III Institute of Health in Madrid, who was involved in the Spanish study. The results have also been posted to the medRxiv server.
- Differences in the male and female immune-system response could explain the divergent risks, says Jessica Metcalf, a demographer at Princeton University, New Jersey. “The female immune system might have an edge by detecting pathogens just a bit earlier,” she says.
- The immune system might also explain the much higher risk of older people dying from the virus. As the body ages, it develops low levels of inflammation, and C19 could be pushing the already overworked immune system over the edge, says Metcalf. Worse outcomes for people with C19 tend to be associated with a ramped-up immune response, she says.
- The study in England also compared results from different ethnic groups. Mortality and morbidity statistics suggest that Black and South Asian people in England are more likely to die or to be hospitalized. But the analysis, led by Helen Ward, an epidemiologist at Imperial College London, found that although Black and South Asian people were much more likely to have been infected than were white people, they were no more likely to die of C19.
- Researchers note that there is a marked difference in IFR estimates between some countries, especially for people aged 65 and older3. For instance, an antibody-prevalence study in Geneva estimated an IFR of 5.6% for people aged 65 and older4. This figure was lower than were estimates in Spain, which comes to about 7.2% for men and women aged 80 or more, and in England, which found an IFR of 11.6% for people aged 75 or older.
- There could be many explanations for the differences, says Andrew Azman, an infectious-disease epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who was part of the Geneva study.
- Countries with higher rates of co-morbidities, such as diabetes, obesity and heart disease, will have a higher IFR. However, nations with health-care systems that are better able to deal with people who are severely ill with C19, or where hospitals were not overwhelmed at the peak of the epidemic, will have better survival rates, he says.
- Some of the differences could be attributed to how the different studies were conducted, say researchers. For example, differences in the reliability of antibody tests used in the different studies, how C19 deaths were recorded and how researchers chose to divide populations by age.
- There is some uncertainty in the data, so the estimates between studies might not be as different as they might seem, says Lucy Okell, an epidemiologist at Imperial College London, who was involved in the English study.
- But a big factor in the different death rates reported between countries seems to be whether the virus spread in nursing homes or elderly-care facilities, says Salje.
- In these places, people in fragile health live in close-knit environments where the virus can spread rapidly. When the English study took into account care-home deaths, the IFR in people aged 75 or older jumped from 11.6% to 18.7%. Salje estimates that the IFR for Canada, where some 85% of deaths occurred in nursing homes, would be significantly higher than that for Singapore, where nursing homes accounted for only 8% of deaths.
- Although fatality estimates are important for understanding the risk of viral spread to people in different age groups, they don’t tell the full story of the toll C19 takes, says Kilpatrick. “There is a fascination with death, but C19 appears to cause a substantial amount of long-term illness,” he adds.
2. Researchers think THC in marijuana may be able to treat deadly COVID complication
- Top University of South Carolina researchers think the chemical in marijuana that induces a “high” may be effective in treating a potentially lethal coronavirus complication, according to three newly released studies
- The studies, co-published by Prakash Nagarkatti, found THC, the most potent mind-altering chemical in cannabis, can — in mice — prevent a harmful immune response that causes Acute Respiratory Distress Syndrome (ARDS) and cause a significant increase in healthy lung bacteria.
- The studies, published in Frontiers in Pharmacology, the British Journal of Pharmacology and the International Journal of Molecular Sciences, were conducted by giving mice a toxin that triggered the harmful immune reaction that causes ARDS and then injecting mice with THC, according to the studies’ abstracts.
- “The underlying mechanism is your immune system goes haywire and starts destroying your lungs and all your other organs,” Nagarkatti said of ARDS.
- “Its’ like a car where you’re putting on a lot of accelerator, but the brakes aren’t working,” Nagarkatti said. “Basically what’s going to happen is your car is going to crash because you can’t stop it. And that’s basically what’s happening with ARDS.”
- Over dozens of experiments in the three separate studies, 100% of the mice given THC survived, Nagarkatti told The State.
- While the many differences between mice and humans mean lab results in mice don’t always directly translate into real-life results for humans, Nagarkatti was blown away at the effectiveness of how effective THC was in treating ARDS.
- There is no FDA-approved drug right now to treat ARDS, Nagarkatti said.
- The experiments were so effective, Nagarkatti has recommended health officials begin human trials with THC, he said.
- However, that doesn’t mean it’s a good idea for people to smoke marijuana if they think they have coronavirus, he said. Since THC suppresses the immune response, smoking marijuana recreationally can actually make a coronavirus infection worse.
- “I just want to make sure our research is not interpreted as marijuana is good for C19,” Nagarkatti said “If you start using THC early on it might worsen the effect because it suppresses the immune system.”
- In coronavirus cases, Nagarkatti’s research shows THC could be tried — if the drug is approved for human trials — if a patient develops the severe ARDS side effect, but not necessarily all C19 cases.
- This is not the first study that shows chemicals contained in marijuana may be useful in treating C19. A July study from the Medical College of Georgia at Augusta University found cannabidiol, or CBD, can reduce the body’s harmful response to coronavirus. CBD, which does not cause a “high,” is already widely available in South Carolina retail stores.
- Marijuana legalization group NORML hailed the development as an addition to growing evidence that the chemicals in marijuana may treat illnesses such as C19 or other illnesses. However, the group advised caution with these early results and warned of grifters who could seek to exploit pot’s positive press.
- “The data at this point is preliminary at best and the public needs to be vigilant against predatory marketers prematurely hailing certain cannabis or CBD-specific products as supposed COVID treatments or cure-alls,” said NORML spokesman Paul Armentano.
3. Drop in Brazilian C19 cases prompts herd immunity questions
- An unexpectedly positive turn for Brazilian cities once plagued with the coronavirus pandemic is raising fresh questions about herd immunity.
- A new report in the Washington Post described how the impoverished city of Manaus saw hospitalizations plummet even though it had never imposed a lockdown or taken the other drastic containment measures imposed in Asia and Europe. It’s also testing far more residents than it once did.
- Initially, medical experts believed that between 60% and 70% of the population needed to develop antibodies to reach collective immunity, but Manaus never got past 20%. And the Amazonian city of 2 million suffered three times as many deaths as normal in the spring.
- There are too many unknown variables to be sure, however, in the broader debate about virus transmission and the level that must be crossed before the number of those infected begins to taper — especially in large cities like the Amazonas capital.
- Many researchers believe that collective immunity works differently in a live outbreak like coronavirus than in something like the measles. The virus doesn’t vanish at a specific point, but the transmission decelerates until it’s eradicated.
- They report that while stringent restrictions are effective, once the virus infects a critical mass, a resurgence in cases is unlikely.
- While the concept of herd immunity has long been used to explain the purpose of mass vaccination campaigns, now the answer seems to be more complex.
- Scientists have been studying the possibility that individual variations in vulnerability reduce the ratio of infection at which herd immunity may be achieved. Some, scrutinizing data from European cities, theorize that herd immunity could be reached at rates lower than 20%.
- Many other cities around the globe that were once devastated by coronavirus have begun to reopen without second waves, with some speculating that collective immunity has been reached.
- Harvard epidemiologists have hypothesized that parts of London and New York have already achieved “substantial immunity.” The same is said by health officials in highly dense areas like India’s Mumbai, though the first recorded C19 re-infection was just confirmed in Hong Kong.
- Swedish health experts claimed they too had achieved herd immunity while abstaining from recommended procedures like mask-wearing and harsh lockdowns.
- Residents of Manaus, meanwhile, are hoping that infections remain at bay.
- Mayor Arthur Virgílio Neto — who has had the virus himself — has admitted that if a second wave did hit, the city’s capacities would once again be “overwhelmed.”
4. Children and young people have less severe C19 than adults and death is exceptionally rare
- Children and young people have less severe C19 than adults and death is exceptionally rare, only occurring in children with serious underlying conditions, confirms a study published by The BMJ today.
- However, the findings also show that children of Black ethnicity were disproportionately severely affected by C19 infection.
- Children and young people make up only 1-2% of cases of C19 worldwide, and the vast majority of reported infections in children are mild or asymptomatic, with few recorded deaths.
- As such, there has been less information on ethnicity, underlying conditions (comorbidities), and outcomes for children with C19 than in adults.
- To address this knowledge gap, UK researchers in the ISARIC4C consortium analysed data from 651 children and young people (aged less than 19 years) with C19 admitted to 138 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020.
- The median age of patients in the study was 4.6 years, predominantly male (56%) and of white ethnicity (57%), with most (58%) children having no known comorbidities.
- The main outcome measures were admission to critical care (a high dependency unit or intensive care unit), death in hospital, or meeting the World Health Organization definition for multisystem inflammatory syndrome (MIS-C) – a rare condition thought to be linked to C19.
- Patients were tracked for a minimum of two weeks (to 17 July 2020), during which time 18% (116) children were admitted to critical care. Those aged younger than 1 month, aged 10-14 years, and of black ethnicity were more likely to be admitted to critical care.
- Six children (1%) died in hospital, all of whom had profound comorbidity. This is a “strikingly low” fatality rate compared with 27% across all ages (0-106 years) over the same time period, note the authors.
- 11% of children met the WHO definition for MIS-C. These children were older (average age 10.7 years) and more likely to be of non-white ethnicity.
- These children were also more likely to be admitted to critical care, show symptoms such as fatigue, headache, muscle pain and sore throat, and have a low blood platelet count, but there were no deaths in this group.
- This is an observational study, so can’t establish cause, and the researchers point to some limitations that may have affected their results.
- However, they say this large study not only gives a detailed picture of the clinical characteristics, risk factors, and outcomes of C19 in children, it should also help to refine the WHO criteria for multisystem inflammatory syndrome.
- As such, they conclude that severe disease is rare and death is exceptionally rare in children admitted to hospital with C19, but that ethnicity seems to be a risk factor for more severe illness.
5. Extensive Search for C19 Drugs Finds Promising Compounds Originally Developed for SARS
- An extensive search and testing of current drugs and drug-like compounds has revealed compounds previously developed to fight SARS might also work against C19.
- Using the National Drug Discovery Centre, researchers from the Walter and Eliza Hall Institute identified drug-like compounds that could block a key coronavirus protein called PLpro. This protein, found in all coronaviruses, is essential for the virus to hijack and multiply within human cells, and disable their anti-viral defenses.
- Initially developed as potential treatments for SARS, the compounds prevented the growth of the coronavirus in the laboratory.
- The discovery, published yesterday in The EMBO Journal, was led by Professor David Komander, Professor Marc Pellegrini, Professor Guillaume Lessene and Dr Theresa Klemm.
At a glance
- Australian researchers have identified a molecular target for potential new C19 treatments
- A chemical compound, originally discovered to inhibit SARS, shows promise for halting the growth of the C19 virus
- The discoveries were made by leveraging the capabilities of the National Drug Discovery Centre and ANSTO’s Australian Synchrotron, and may underpin the development of new drugs for C19
Targeting a key viral protein
- Coronaviruses, including the viruses that cause C19 and SARS, all contain a protein called PLpro, which allows the virus to hijack human cells and disable their anti-viral defenses.
- Professor Komander said PLpro belonged to a family of proteins called ‘deubiquitinases’, which his team had studied for the last 15 years in a range of diseases.
- “When we looked at how the coronavirus functions, it became clear that the PLpro deubiquitinase was a key component of the virus – as it is in other coronaviruses, including the SARS-CoV-1 virus, which causes SARS,” he said.
- “We quickly established the VirDUB program to investigate how PLpro functions and what it looks like. These are critical first steps towards discovering new drugs that could be potential therapies for C19.”
- Using ANSTO’s Australian Synchrotron, the VirDUB team rapidly ascertained how PLpro interacts with human proteins – homing in on a target that could be blocked by new drugs.
Discovering new medicines
- The National Drug Discovery Centre was critical to rapidly search for drugs that could block PLpro.
- “We scanned thousands of currently listed drugs, as well as thousands of drug-like compounds, to see if they were effective in blocking the SARS-CoV-2 PLpro,” Professor Komander said.
- “While existing drugs were not effective in blocking PLpro, we discovered that compounds developed in the last decade against SARS, could prevent the growth of coronavirus in pre-clinical testing in the laboratory.”
- The next step is to turn these compounds into drugs that could be used to treat C19, Professor Komander said.
- “We now need to develop the compounds into medicines, and make sure they are safe for patients.
- “Importantly, drugs that are able to inactivate PLpro may be useful not just for C19 but may also work against other coronavirus diseases, as they emerge in the future.”
C. Improved & Potential Treatments
1. Antiviral used to treat cat coronavirus also works against coronavirus
- Researchers at the University of Alberta are preparing to launch clinical trials of a drug used to cure a deadly disease caused by a coronavirus in cats that they expect will also be effective as a treatment for humans against C19.
- “In just two months, our results have shown that the drug is effective at inhibiting viral replication in cells with coronavirus,” said Joanne Lemieux, a professor of biochemistry in the Faculty of Medicine & Dentistry.
- “This drug is very likely to work in humans, so we’re encouraged that it will be an effective antiviral treatment for C19 patients.”
- The drug is a protease inhibitor that interferes with the virus’s ability to replicate, thus ending an infection. Proteases are key to many body functions and are common targets for drugs to treat everything from high blood pressure to cancer and HIV.
- First studied by U of A chemist John Vederas and biochemist Michael James following the 2003 outbreak of severe acute respiratory syndrome (SARS), the protease inhibitor was further developed by veterinary researchers who showed it cures a disease that is fatal in cats.
- The work to test the drug against the coronavirus was a co-operative effort between four U of A laboratories, run by Lemieux, Vederas, biochemistry professor Howard Young and the founding director of the Li Ka Shing Institute of Virology, Lorne Tyrrell. Some of the experiments were carried out by the Stanford Synchrotron Radiation Lightsource Structural Molecular Biology program.
- Their findings were published today in the peer-reviewed journal Nature Communications after first being posted on BioRxIV, a research website.
- “There’s a rule with COVID research that all results need to be made public immediately,” Lemieux said, which is why they were posted before being peer-reviewed.
- She said interest in the work is high, with the paper being accessed thousands of times as soon as it was posted.
- Lemieux explained that Vederas synthesized the compounds, and Tyrrell tested them against the SARS-CoV-2 virus in test tubes and in human cell lines. The Young and Lemieux groups then revealed the crystal structure of the drug as it binds with the protein.
- “We determined the three-dimensional shape of the protease with the drug in the active site pocket, showing the mechanism of inhibition,” she said. “This will allow us to develop even more effective drugs.”
- Lemieux said she will continue to test modifications of the inhibitor to make it an even better fit inside the virus.
- But she said the current drug shows enough antiviral action against coronavirus to proceed immediately to clinical trials.
- “Typically for a drug to go into clinical trials, it has to be confirmed in the lab and then tested in animal models,” Lemieux said. “Because this drug has already been used to treat cats with coronavirus, and it’s effective with little to no toxicity, it’s already passed those stages and this allows us to move forward.”
- “Because of the strong data that we and others have gathered we’re pursuing clinical trials for this drug as an antiviral for C19.”
- The researchers have established a collaboration with Anivive Life Sciences, a veterinary medicine company that is developing the drug for cats, to produce the quality and quantity of drug needed for human clinical trials. Lemieux said it will likely be tested in Alberta in combination with other promising antivirals such as remdesivir, the first treatment approved for conditional use in some countries including the United States and Canada.
2. Main approaches to the treatment of coronavirus
- Researchers from Sechenov University together with Russian and Iranian colleagues described currently known approaches to the treatment of C19 infection. In the paper published in Journal of Molecular Medicine, they wrote about how different groups of drugs worked and how promising each approach was.
- The coronavirus is a close relative of two other viruses (SARS-CoV and MERS-CoV) that triggered epidemics in 2003 and 2013-2015. Most often, the disease is accompanied by fever, dry cough, increased fatigue, and loss of taste and smell. Most symptoms are associated with an overreaction of the patient’s immune system, which, in severe cases, causes damage to lung tissue and systemic inflammation.
- The first approach considered in the article is immunotherapy. It is known that antibodies contained in the serum of people who have had a viral disease can speed up the recovery of other patients. Despite the simplicity of this method, it has several limitations: the number of potential donors is still small, the activity of antibodies decreases over time (which is why the serum from the patients who had the disease long ago is less valuable), and the antibodies themselves can help the virus spread in the body – a phenomenon known as antibody-dependent enhancement of infection.
- Similarly, we can use T-lymphocytes – cells that can destroy damaged or infected cells of the body. Scientists have noticed that the number of T-cells of the CD8+ subpopulation is significantly reduced in patients with C19, and the more severe the disease the lower this number. T-cells directed against a specific virus can be produced in vitro and offered to patients as therapy.
- Another area of research is related to the suppression of certain enzymes, in particular AAK1 and GAK, which are needed for the virus to enter a cell. Some of the drugs that act as inhibitors of these enzymes have already been tested and used, although for another purpose, such as, for example, the treatment of rheumatoid arthritis (this approach is called ‘drug repurposing’).
- ‘Analysis of clinical trials registered in ClinicalTrials.gov has shown a wide variety of therapeutic agents offered for the treatment of C19. And, of course, most of them are associated with the use of previously known drugs used in the treatment of other diseases,’ commented Anastasia Shpichka, one of the authors of the study, a leading researcher at the Institute for Regenerative Medicine, Sechenov University.
- There are other ways to prevent the virus from entering cells. Since the receptor that is built into the cell membrane and lets the virus inside is known (this is the ACE2 protein), it is possible to create an analogue that will bind to viral particles and ‘distract’ them from the patient’s cells. Such analogues of the ACE2 receptor have already been developed, tested and shown to slow down the spread of the virus in the body, but not stop it, which indicates the presence of other entry points into human cells.
- The use of antiviral drugs gives contradictory results. Remdesivir, which showed good efficacy against coronavirus in some studies, did not bring noticeable benefits in others. Chloroquine, used to treat malaria, was considered a promising drug, but its side effects do not allow it to be recommended for the treatment of C19. Attempts to use HIV medications against the coronavirus also yield mixed results.
- One more direction in the fight against C19 is suppression of excessive immune system reaction, which especially affects the lung tissue. One treatment option may be mesenchymal stem cells, used in the treatment of inflammatory and autoimmune diseases. Studies of the effectiveness of this method in the treatment of C19 are already underway. Another class of drugs that limit inflammatory response is corticosteroids. They can reduce mortality among patients with severe disease.
- Despite the efforts of scientists from all over the world, aimed at finding an effective C19 treatment, the optimal algorithm has not yet been found. The key to creating a drug can be either a discovery as part of one of these approaches or a new solution, for example, found at the intersection of scientific disciplines or borrowed from the experience of treating other diseases.
D. Vaccines & Testing
1. We Will Have a C19 Vaccine Soon
Opinion by Alan Bernstein, Member of the Canadian C19 Vaccine Task Force
- On January 11, a Chinese team reported online the RNA genome sequence of a novel coronavirus causing a strange new pneumonia-like disease in Wuhan, China. Within 48 hours, scientists at Moderna, a Massachusetts biotechnology company, had the entire genome synthesized. Remarkably, about 60 days later, the company, in collaboration with the Vaccine Research Center at the National Institutes of Health, began a human Phase 1 clinical trial of an RNA vaccine.
- Since C19 began its rapid spread across the world, scientists have worked with remarkable speed at trying to understand the virus—how it causes disease; how it spreads; why some people are asymptomatic while others die; how to develop new, or repurpose old, drugs; and how to create a safe and effective vaccine as quickly as possible. The C19 story illustrates the tremendous capacity and speed of science in the 21st century, and the power of international collaboration. I am a member of the Canadian C19 Vaccine Task Force, charged by the government to recommend C19 vaccines that the country should purchase for its population. I am optimistic that the world will have a safe and effective vaccine by the end of this year or early 2021. However, I worry that people everywhere won’t have equal access to it.
- The history of vaccinology goes back to the late 1700s when Edward Jenner developed the first vaccine, for smallpox, a turning point in the war between microbes and humans. A great triumph of modern science, vaccines rely entirely on the activation of the body’s own protective immunological mechanisms. Vaccines prevent disease, are inexpensive, are easy to deliver, and have long-lasting effects. They are also the sole medicine that benefits not only vaccinated individuals but also those around them by interrupting the pathogen’s transmission within the community.
- Back in the spring, most scientists, including Anthony Fauci, the top infectious-disease expert in the U.S., predicted that a vaccine would take at least 12–18 months to deliver. That time frame was viewed as wildly optimistic, even reckless, given the more typical four to six, sometimes as many as 10 to 15, years that vaccine development typically requires. Today, most scientists working in infectious disease, including Fauci, are saying the United States will know whether there’s an effective C19 vaccine by the end of the year or early 2021, and one could become available by the end of 2021. That incredible speed is not being accomplished at the expense of safety; rather, it is the result of unprecedented collaboration across borders, academia, and industry.
- The ideal vaccine will do three things: protect individuals from becoming infected, prevent life-altering effects for those who do get C19, and block transmission of the virus to others. The vaccine does not need to be 100% effective at all three to be a powerful addition to our defenses against this virus.
- More than 100 vaccine candidates, including one by Moderna, are being developed around the world and about 36 have already entered human clinical trials. My optimism is not simply based on a numbers game. Nine vaccine candidates have now entered Phase 3 human trials, the final step before regulatory approval. The fact that entirely different approaches to vaccine development are all yielding promising early results is highly encouraging.
- I am also hopeful because of the science behind these vaccines. The technology powering RNA vaccines, for example, was initially developed to deliver genes into the body to reprogram cells to behave like stem cells. This is the kind of science that is changing all of vaccinology, not just C19 vaccine development.
- In the case of the coronavirus, the protein that scientists are testing as a vaccine candidate is the result of advances in the study of protein structures. The protein in question, the spike protein, is the knobbly protrusions seen in all the illustrations of coronavirus. Because most proteins have complex three-dimensional shapes, the goal is to pick the right version of the spike protein as a vaccine so that when it is introduced into someone’s body, the immune system immediately recognizes it as foreign and starts to mount a powerful immune response directed at the spike protein. The result is that the immune system is then pre-armed and ready to immediately swing into action if a person is subsequently infected by the virus.
- The science is paying off. Novavax, a Maryland-based company working on this type of vaccine, recently reported the results of its Phase 1 trial. The levels of antibodies generated were stunning, about four times higher than those in individuals who are recovering from a C19 infection.
- Scientists are also using different strains of another virus, adenovirus, as a vector or a missile to deliver genes that code for these same spike proteins and that also provoke an immune response. The vector has been engineered in the lab to be replication-defective; that is, the vector is able to deliver the spike gene into humans but once it’s done its job, the vector cannot replicate any further. At least three groups are testing these vectors. A University of Oxford group, in partnership with AstraZeneca, has employed an adenovirus from chimpanzees and has already entered Phase 3 trials in humans. The Beth Israel Deaconess Medical Center group, in partnership with Janssen Pharmaceutica, is using Ad26, a human adenovirus, and the Chinese-based CanSino Biologics has begun Phase 3 trials with yet another human adenovirus, Ad5.
- These examples are not just beautiful science (although they are beautiful science). By harnessing the increased power of the biological sciences, researchers are developing entirely new ways of rapidly developing vaccines.
- My optimism doesn’t stop with these early results, although they are key. I’m also encouraged because at least five very different approaches (I’ve walked through only three above) are being explored to make a vaccine. As we say in Canada, if you want to win, you have to take many shots on goal.
- Equally important is the unprecedented global collaboration among scientists around the world, as well as the high degree of cooperation between scientists and clinicians, biopharmaceutical companies, government, philanthropic funders, and regulators. They are all working together toward the common goal of developing as quickly as possible a safe and effective vaccine against C19.
- I don’t know which of the vaccine candidates undergoing clinical testing in humans will ultimately be shown to be safe and effective. They might all prove effective, albeit in different age groups or in people with different preexisting conditions. But the encouraging news is that all of the vaccine candidates that have entered trials in humans so far are safe and have elicited high levels of antibodies against C19. Some have also been shown to activate the cellular arm of our immune system, another crucial component of our defenses against foreign pathogens.
- The public-health imperative to obtain a safe and effective vaccine as quickly as possible goes hand in hand with the mandate that the approval process be above any political considerations and solely based on data from the clinical trials. Anything else risks losing the public’s confidence in a vaccine or, in a worst-case scenario, might result in a vaccine that is less effective than those that might be approved later, or the widespread administration of a vaccine that turns out to have serious adverse side effects. That would be a public-health tragedy.
- Developing a vaccine and getting proper regulatory approval are just the first two steps. The world will need billions of doses and many billions of dollars to produce and disseminate the vaccine. My main concern in this whole process is that governments will not spend enough on manufacturing the vaccine to administer it to every adult on the planet. Ensuring equitable access to a vaccine is imperative, and not just a generous gesture by wealthy nations. It’s also in their best interests. If the virus is anywhere, it’s everywhere. Nations will need to show the same willingness to cooperate as the scientists from around the world, and the same generosity of spirit demonstrated by the nearly half a million people who will have volunteered to be part of a C19 vaccine trial by the time this is all over.
- The United States, the wealthiest nation in the world and historically the first among nations in its generosity and leadership, has yet to contribute to the various multilateral initiatives established to purchase vaccines for the developing world. To date, 75 industrialized nations have agreed to finance vaccine purchases for 90 lower-income countries. But the U.S. is not yet one of them.
- The cost of manufacturing enough doses to vaccinate every adult on the planet will be in the hundreds of billions of dollars. But compared with the trillions of dollars that governments are now spending to assist individuals who have lost their jobs and to prop up their economies, $100–200 billion is a bargain and an insurance policy that developed countries cannot afford not to buy.
- If people everywhere—regardless of their gender, citizenship, ethnicity, skin color, or ability to pay—have equal and timely access to a safe and effective vaccine against C19, the world will come out of this pandemic stronger than it went in. The C19 pandemic has put other global challenges, including climate change and the development of accessible forms of sustainable energy, on the back burner. When this pandemic is over, we need to renew our focus on the problems that faced our planet before C19. If we can eradicate C19 through science and global collaboration, just imagine what else we can do.
2. Researchers develop a fast, accurate, low-cost C19 test
- A new low-cost diagnostic test for coronavirus disease 2019 (C19) quickly delivers accurate results without the need for sophisticated equipment, according to a study published August 27 2020 in the open-access journal PLOS Pathogens by Teng Xu of the Vision Medicals Center for Infectious Diseases, Tieying Hou of the Guangdong Academy of Medical Sciences, Bing Gu of the Affiliated Hospital of Xuzhou Medical University, Jianwei Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues.
- The surging demand for rapid screening and identification of C19 poses great diagnostic challenges. Metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) have been the most commonly used molecular methods for diagnosing C19, but each has its own limitations. For example, sequencing is costly and has a turnaround time of nearly one day, while RT-PCR requires specialized equipment and is difficult to deploy at a large scale. A lack of rapid and accurate molecular diagnostic tools has hampered efficient public health responses to the viral threat.
- In the new study, the researchers developed an alternative C19 test by leveraging CRISPR-based technology, which has been widely used in recent years for gene editing. The assay, named CRISPR-COVID, enables high-throughput detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CRISPR-COVID delivers comparable sensitivity and specificity as mNGS within as short as 40 minutes. When produced at a large scale, the material cost of a CRISPR-COVID test could be less than 70 cents, suggesting that CRISPR-COVID is a competitive alternative not only technologically but also financially.
- The authors note, “In this study, we developed an isothermal, CRISPR-based diagnostic for C19 with near single-copy sensitivity.” and “We demonstrated a CRISPR-based assay for C19 that offered shorter turn-around time and great diagnostic value, even in under-resourced settings without the need of thermal cyclers.”
E. Concerns & Unknowns
1. Children With No Symptoms May Shed Coronavirus for Weeks
- New research suggests that children can shed the coronavirus even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease, according to an invited commentary by Children’s National Hospital doctors that accompanies this new study published online today (August 28, 2020) in JAMA Pediatrics. The commissioned editorial, written by Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Diseases, and Meghan Delaney, D.O., M.P.H., chief of the Division of Pathology and Lab Medicine, provides important insight on the role children might play in the spread of C19 as communities continue to develop public health strategies to reign in this disease.
- The study that sparked this commentary focused on 91 pediatric patients followed at 22 hospitals throughout South Korea. “Unlike in the American health system, those who test positive for C19 in South Korea stay at the hospital until they clear their infections even if they aren’t symptomatic,” explains Dr. DeBiasi.
- The patients here were identified for testing through contact tracing or developing symptoms. About 22% never developed symptoms, 20% were initially asymptomatic but developed symptoms later, and 58% were symptomatic at their initial test. Over the course of the study, the hospitals where these children stayed continued to test them every three days on average, providing a picture of how long viral shedding continues over time.
- The study’s findings show that the duration of symptoms varied widely, from three days to nearly three weeks. There was also a significant spread in how long children continued to shed virus and could be potentially infectious.
- While the virus was detectable for an average of about two-and-a-half weeks in the entire group, a significant portion of the children — about 20% of the asymptomatic patients and about 50% of the symptomatic ones — were still shedding virus at the three-week mark.
- Drs. DeBiasi and Delaney write in their commentary that the study makes several important points that add to the knowledge base about C19 in children. One of these is the large number of asymptomatic patients — about a fifth of the group followed in this study. Another is that children, a group widely thought to develop mostly mild disease that quickly passes, can retain symptoms for weeks. A third and important point, they say, is the duration of viral shedding. Even asymptomatic children continued to shed virus for a long time after initial testing, making them potential key vectors.
- However, the commentary authors say, despite these important findings, the study raises several questions. One concerns the link between testing and transmission. A qualitative “positive” or “negative” on testing platforms may not necessarily reflect infectivity, with some positives reflecting bits of genetic material that may not be able to make someone sick or negatives reflecting low levels of virus that may still be infectious.
- Testing reliability may be further limited by the testers themselves, with sampling along different portions of the respiratory tract or even by different staff members leading to different laboratory results. It’s also unknown whether asymptomatic individuals are shedding different quantities of virus than those with symptoms, a drawback of the qualitative testing performed by most labs. Further, testing only for active virus instead of antibodies ignores the vast number of individuals who may have had and cleared an asymptomatic or mild infection, an important factor for understanding herd immunity.
- Lastly, Drs. DeBiasi and Delaney point out, the study only tested for viral shedding from the respiratory tract even though multiple studies have detected the virus in other bodily fluids, including stool. It’s unknown what role these other sources might play in the spread of this disease.
- Drs. DeBiasi and Delaney note that each of these findings and additional questions could affect public health efforts continually being developed and refined to bring C19 under control in the U.S. and around the world. Children’s National has added their own research to these efforts, with ongoing studies to assess how C19 infections proceed in children, including how antibodies develop both at the individual and population level.
- “Each of these pieces of information that we, our collaborators and other scientists around the world are working to gather,” says Dr. DeBiasi, “is critical for developing policies that will slow the rate of viral transmission in our community.”
2. Rigid Social Distancing Rules for C19 Based on Outdated Science
- Rules which stipulate a single specific physical distance (1 or 2 meters) between individuals to reduce the spread of C19 are based on outdated science and experiences of past viruses, argue researchers in The BMJ on August 25, 2020.
- Such rules are based on an over-simplistic dichotomy describing viral transfer by either large droplets or small airborne droplets emitted in isolation without accounting for the exhaled air, say Nicholas Jones at the University of Oxford and colleagues.
- In reality, transmission is more complex, involving a continuum of droplet sizes and an important role of the exhaled air that carries them, they explain.
- Evidence suggests that smaller airborne droplets laden with C19 can travel more than 2 meters by activities such as coughing and shouting, and may spread up to 7-8 meters concentrated in exhaled air from an infected person.
- As such, they say distancing rules need to take account of the multiple factors that affect risk, including type of activity, indoor versus outdoor settings, level of ventilation, and whether face coverings are worn.
- Viral load of the emitter, duration of exposure, and susceptibility of an individual to infection are also important, they add.
- “This would provide greater protection in the highest risk settings but also greater freedom in lower-risk settings, potentially enabling a return towards normality in some aspects of social and economic life,” they write.
- To facilitate this, they discuss how transmission risk may vary with setting, occupancy level, contact time, and whether face coverings are worn.
- For example, in the highest risk situations, such as a crowded bar or nightclub, physical distancing beyond 2 meters and minimizing occupancy time should be considered, while less stringent distancing is likely to be adequate in low-risk scenarios.
- They say further work is needed to examine areas of uncertainty and extend the guide to develop specific solutions to classes of indoor environments occupied at various usage levels.
- “Physical distancing should be seen as only one part of a wider public health approach to containing the C19 pandemic,” they conclude.
- “Physical distancing should be used in combination with other strategies to reduce transmission risk, including handwashing, regular surface cleaning, protective equipment, and face coverings where appropriate, strategies of air hygiene, and isolation of affected individuals.”
3. CDC study reveals evidence of C19 spreading in airplanes
- C19 has been shown to spread on airplanes even among asymptomatic travelers, according to a new study from the CDC.
- The study, which was published in the journal Emerging Infectious Diseases, found evidence of transmission on an evacuation flight from Milan, Italy, to Seoul, South Korea in late March.
- Before boarding the flight, around 300 passengers were screened for virus symptoms and given an N95 mask, researchers said.
- When the passengers arrived, they were quarantined by the government for two weeks and regularly tested, according to the study
- Six of the travelers — who were asymptomatic — tested positive at the start of the quarantine, researchers said.
- On the final day of the quarantine, a seventh passenger tested positive, despite previously receiving negative results, the report said.
- The passenger — who had been seated three rows ahead of asymptomatic travelers — had worn her N95 mask for the entire duration of the flight except to use the bathroom.
- Researchers noted that the same toilet was used by at least one of the infected travelers.
- They concluded that it’s “highly likely” that she caught the virus from the evacuation flight.
- “Given that she did not go outside and had self-quarantined for 3 weeks alone at her home in Italy before the flight and did not use public transportation to get to the airport, it is highly likely that her infection was transmitted in the flight via indirect contact with an asymptomatic patient,” researchers wrote.
4. Estrogen may lessen severity of C19 symptoms in women
- Why are men at greater risk than women for more severe symptoms and worse outcomes from C19 regardless of age?
- In an effort to understand why this occurs, scientists at Wake Forest School of Medicine conducted a review of published preclinical data on sex-specific hormone activity, especially estrogen. The review is published in the September online issue of the journal Current Hypertension Reports.
- “We know that coronavirus affects the heart and we know that estrogen is protective against cardiovascular disease in women, so the most likely explanation seemed to be hormonal differences between the sexes,” said the lead author of the review, Leanne Groban, M.D., professor of anesthesiology at Wake Forest School of Medicine, part of Wake Forest Baptist Health.
- Groban’s researchers said the published literature indicated that the angiotensin-converting enzyme2 (ACE2), which is attached to cell membranes in the heart, arteries, kidneys and intestines, is the cellular receptor of the coronavirus responsible for C19 infections, and helps bring the virus into the cells of those organ systems.
- The review, they said, also pointed to estrogen’s lowering the level of ACE2 in the heart, which may modulate the severity of C19 in women. Conversely, higher levels of ACE2 in tissues could account for why symptoms are worse in men than women, Groban said.
- “We hope that our review regarding the role of estrogenic hormones in ACE2 expression and regulation may explain the gender differences in C19 infection and outcomes, and serve as a guide for current treatment and the development of new therapies,” Groban said.
5. Scientists are reporting several cases of C19 reinfection — but the implications are complicated
- Following the news this week of what appears to have been the first confirmed case of a C19 reinfection, other researchers have been coming forward with their own reports. One in Belgium, another in the Netherlands. And now, one in Nevada.
- What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted C19 a second time. Rather, it’s that his second bout was more serious than his first.
- Immunologists had expected that if the immune response generated after an initial infection could not prevent a second case, then it should at least stave off more severe illness. That’s what occurred with the first known reinfection case, in a 33-year-old Hong Kong man.
- Still, despite what happened to the man in Nevada, researchers are stressing this is not a sky-is-falling situation or one that should result in firm conclusions. They always presumed people would become vulnerable to C19 again some time after recovering from an initial case, based on how our immune systems respond to other respiratory viruses, including other coronaviruses. It’s possible that these early cases of reinfection are outliers and have features that won’t apply to the tens of millions of other people who have already shaken off C19.
- “There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?”
- But with more reinfection reports likely to make it into the scientific literature soon, and from there into the mainstream press, here are some things to look for in assessing them.
What’s the deal with the Nevada case?
- The Reno resident in question first tested positive for coronavirus in April after coming down with a sore throat, cough, and headache, as well as nausea and diarrhea. He got better over time and later tested negative twice.
- But then, some 48 days later, the man started experiencing headaches, cough, and other symptoms again. Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia.
- Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first.
What happens when we get C19 in the first case?
- Researchers are finding that, generally, people who get C19 develop a healthy immune response replete with both antibodies (molecules that can block pathogens from infecting cells) and T cells (which help wipe out the virus). This is what happens after other viral infections.
- In addition to fending off the virus the first time, that immune response also creates memories of the virus, should it try to invade a second time. It’s thought, then, that people who recover from C19 will typically be protected from another case for some amount of time. With other coronaviruses, protection is thought to last for perhaps a little less than a year to about three years.
- But researchers can’t tell how long immunity will last with a new pathogen (like the coronavirus) until people start getting reinfected. They also don’t know exactly what mechanisms provide protection against C19, nor do they know what levels of antibodies or T cells are required to signal that someone is protected through a blood test. (These are called the “correlates of protection.”)
Why do experts expect second cases to be milder?
- With other viruses, protective immunity doesn’t just vanish one day. Instead, it wanes over time. Researchers have then hypothesized that with SARS-CoV-2, perhaps our immune systems might not always be able to prevent it from getting a toehold in our cells — to halt infection entirely — but that it could still put up enough of a fight to guard us from getting really sick. Again, this is what happens with other respiratory pathogens.
- And it’s why some researchers actually looked at the Hong Kong case with relief. The man had mild to moderate C19 symptoms during the first case, but was asymptomatic the second time. It was a demonstration, experts said, of what you would want your immune system to do. (The case was only detected because the man’s sample was taken at the airport when he arrived back in Hong Kong after traveling in Europe.)
- “The fact that somebody may get reinfected is not surprising,” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. “But the reinfection didn’t cause disease, so that’s the first point.”
- The Nevada case, then, provides a counterexample to that.
What kind of immune response did the reinfected person generate initially?
- Earlier, we described the robust immune response that most people who have C19 seem to mount. But that was a generalization. Infections and the immune responses they induce in different people are “heterogeneous,” said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago.
- Older people often generate weaker immune responses than younger people. Some studies have also indicated that milder cases of C19 induce tamer immune responses that might not provide as lasting or as thorough of a defense as stronger immune responses. The man in Hong Kong, for example, did not generate antibodies to the virus after his first infection, at least to the level that could be detected by blood tests. Perhaps that explains why he contracted the virus again just about 4 1/2 months after recovering from his initial infection.
- In the Nevada case, researchers did not test what kind of immune response the man generated after the first case.
- “Infection is not some binary event,” Cobey said. And with reinfection, “there’s going to be some viral replication, but the question is how much is the immune system getting engaged?”
- What might be broadly meaningful is when people who mounted robust immune responses start getting reinfected, and how severe their second cases are.
Are people who have C19 a second time infectious?
- As discussed, immune memory can prevent reinfection. If it can’t, it might stave off serious illness. But there’s a third aspect of this, too.
- “The most important question for reinfection, with the most serious implications for controlling the pandemic, is whether reinfected people can transmit the virus to others,” Columbia University virologist Angela Rasmussen wrote in Slate this week.
- Unfortunately, neither the Hong Kong nor the Reno studies looked at this question. But if most people who get reinfected don’t spread the virus, that’s obviously good news.
What happens when people broadly become susceptible again?
- Whether it’s six months after the first infection or nine months or a year or longer, at some point, protection for most people who recover from C19 is expected to wane. And without the arrival of a vaccine and broad uptake of it, that could change the dynamics of local outbreaks.
- In some communities, it’s thought that more than 20% of residents have experienced an initial C19 case, and are thus theoretically protected from another case for some time. That is still below the point of herd immunity — when enough people are immune that transmission doesn’t occur — but still, the fewer vulnerable people there are, the less likely spread is to occur.
- On the flip side though, if more people become susceptible to the virus again, that could increase the risk of transmission. Modelers are starting to factor that possibility into their forecasts.
- A crucial question for which there is not an answer yet is whether what happened to the man in Reno, where the second case was more severe than the first, remains a rare occurrence, as researchers expect and hope. As the Nevada researchers wrote, “the generalizability of this finding is unknown.”
6. My severe C19: It felt like dying in solitary confinement
- C19 is teaching everyone in medicine lessons about health care and public health. Mine have been up close, personal, and frightening.
- One day I was a healthy 44-year-old doctor, CEO of a health care company, and a triathlete who was prepared to do another triathlon. Then I was a C19 patient a few shallow breaths away from being put on a ventilator. A nurse saved me from that fate.
- A journey that made me ponder new questions and opened my eyes to a new sense of purpose and perspective started innocuously enough. The soreness and aches began on a Monday night; a fever followed. I woke up Tuesday morning feeling awful. I got tested and it was official — I was one of the thousands of new C19 patients that day.
- By Friday, I was having trouble taking deep breaths. My pulse oximeter showed 95%. Not bad, but not normal for me — that would have been 99% to 100%. Over the next two days, things got worse.
- Sunday morning, six days after first feeling sick, I walked to the bathroom and felt a new sensation: I was winded and light-headed. My oxygen level was still 97%, but I was breathing much faster. As I sat on the edge of the bathtub, my respiratory rate was 18 breaths per minute (50% higher than usual) and my heart rate was 85 beats per minute (up from my baseline of 50).
- When you come from a family of doctors and lead a company of doctors, getting a second, third, and fourth opinion is easy. Everyone I reached had the same advice: Go to the hospital. Before we left, my wife, Stephanie, called family members, friends, and my colleagues at ChenMed and asked everyone to pray for me. We weren’t sure how things would turn out, and we needed as many people as possible appealing to a higher power on my behalf.
- At the hospital, a CT scan showed C19-related pneumonia in all parts of my lungs. I was given a dose of steroids (dexamethasone) to decrease C19-related inflammation in my lungs, a shot of a blood thinner to prevent blood clots, and was then admitted.
- The hospital was fantastic. I knew many of the doctors, including the chief medical officer and the chief of cardiology. They would walk by the window of my room, knock on the glass, then call my cell and reassure me I was in good hands.
- Even so, I began feeling despondent. It didn’t help that I kept feeling worse and worse. I felt like I was staring into a dark tunnel — standing alone and worrying about myself, my wife and children, my parents, and my company. Sure, nurses would come in frequently, but only fully gowned for two minutes or less. Doctors would review my numbers and then call my phone to speak with me. I was alone, and I was lonely.
- Nights were the worst. That’s when the fevers were highest and my breathing was most labored. I felt like I was wasting away: covered in sweat, unable to bathe or shower, tied down by a web of wires, lines, and tubes and trying desperately to breathe. I got an inkling of what my heart failure patients experience when they cannot breathe due to fluid buildup in their lungs and feel like they are drowning from the inside out.
- I prayed for hope but feared the worst. I knew I was getting sicker, and had just heard that remdesivir, a promising antiviral drug, was in short supply. I was enrolled in a study to receive convalescent plasma — the liquid portion of blood from someone who had recovered from C19 which is filled with antibodies against the virus — but was on the waiting list.
- I knew that everyone was working tirelessly to stop my C19 from progressing, but I was losing ground. Without a firm date for treatment, I felt sad and hopeless.
- On Tuesday night, my ICU nurse was a 6-foot-tall woman from Jamaica named Helen, though I’m pretty sure she had been a drill instructor in another life. If she wanted me to sit on the edge of the bed and I said “no,” we reached an understanding: I sat on the edge of the bed. Helen started her shift by changing my gown and sheets, then helped me take a chlorhexidine towel bath. Those small acts of kindness felt wonderful.
- Despite having trouble breathing, I sometimes fell asleep. Then my breathing would slow and my blood oxygen level would drop to unsafe levels. Helen would open the door to my room and yell, “Chris, c’mon. You’ve got to breathe. Breathe for me.” I knew what she was doing: waking me up so I would breathe faster. When I took faster breaths, my blood oxygen would rise and the alarm attached to my pulse oximeter would stop chirping.
- If I couldn’t breathe on my own, I would be put on a ventilator and, if that happened, my chance of dying would skyrocket. I believe that Helen saved my life that night.
- Around 3 a.m. she came into my room again. When I heard her voice, I immediately started to breathe faster. But this time she had a different message: “Chris, your plasma has arrived,” she told me. “I’m going to get it.”
- “Are you sure?” I asked, since the plasma wasn’t supposed to get to the hospital for a few more days.
- “The blood bank just called,” she replied.
- All I could say was, “Praise God.” It was my first glimmer of hope.
- I received the plasma as the shift was changing in the morning. I wanted to give Helen a hug or at least shake her hand, but the best I could do in the time of coronavirus was to say an emotional “Thank you for getting me through last night” as she headed home.
- The following morning, my brother, who is a cardiologist, called and said remdesivir had been secured for me and I would get my first dose at 11 a.m. That afternoon, I began feeling better. I was able to sit in the chair next to my bed. I wondered if the plasma and remdesivir were working, or whether my body was finally fighting its way back.
- I remained fever-free. When Saturday morning rolled around, my light-headedness had cleared. My breathing felt less labored and I was able to take deeper breaths. My aches were subsiding, and I felt stronger and more alert. I walked around my room without becoming short of breath. I was ready to go home.
- As I was wheeled out of the ICU room, I looked around. When I arrived, half of the rooms — all reserved for C19 patients — were empty. As I left, all of them were full and many of the occupants were on ventilators. I asked to stop for a moment so I could say a prayer for my brothers and sisters with C19.
- Stephanie and my oldest son were waiting outside the hospital in a carport reserved for C19 patients. I was overcome with emotion. We hugged and held each other tight. For the first time since entering the ICU, I realized I would still get to be a husband, father, brother, and son, and would continue to lead ChenMed. I was overwhelmed.
- As I write this, it’s been 20 days since I first started feeling sick, and I am still recovering. I still have questions, but they are far different than the ones I thought about when I was in the hospital.
- I’ve realized how naïve I was about what it is like to be a patient. Coming out of medical training, critical care was one of my strongest skills. I conducted countless blood gasses, which means drawing blood from an artery to test for oxygen and carbon dioxide levels, but never had one done to me. I’ve heard the constant din of hospital bells and alarms, but never from a hospital bed.
- I’ve poked and prodded patients every few hours never knowing what it felt like. I knew that the jumble of cords and wires attached to my patients made it hard for them to move, and now feel foolish for suggesting that they “Try and get some sleep.” And I never could have imagined the feeling of being weighed down and immobilized by sensors and intravenous lines and other tubes.
- The experience of being in an intensive care unit for C19 is making me ponder a whole new set of issues: How can I be a better husband and father? How do I show appreciation for the amazing care that saved my life? How can I convince others of the severity of C19? How can I help health care workers empathize with the pain and anguish of being hospitalized — and alone — so we all rise to the challenges caring for the patients we serve? How can I better lead ChenMed? And how does God want me to use what I learned?
- Before this experience, I thought I knew a lot about C19. I was wrong. But here’s one thing I know for sure: If you haven’t been taking the risk of this pandemic seriously, you should start now.
- When you’re an ICU patient with C19, it is like dying in solitary confinement.
- Christopher Chen is a cardiologist and CEO of ChenMed, which focuses on providing primary care for seniors.
F. The Road Back?
1. Remote-Working Americans Shell Out $30,000 For Tiny Home Offices
- As the C19 pandemic struck fast and hard, years of changes are transforming the economy in a matter of quarters. For instance, the trend of remote work continues to erupt, allowing folks to work at home instead of corporate offices.
- The next-generation work environment could be one’s back yard. People have been shelling out $30,000 for tiny home offices post-pandemic.
- Yahoo Finance said Colorado-based Studio Shed is building tiny home offices for an average cost of $20,000 to $30,000. The sheds are commonly installed in the backyard of a home, allow white-collar folks to work from home but removed from the main house.
- Studio Shed co-founder Mike Koenig said remote working during the pandemic has led to a massive increase in sales this year over the last, increasing 14-fold so far.
- “Recently, we have seen a massive surge in the 80- to 120-square feet option, which is a perfect office size or home gym or kid’s study area,” Koenig said. “We were already seeing some very good growth having started in 2008 just seeing these shifts in the way people work and wanting to spend more time at home and maybe not commute, but starting in March, it’s just been growing significantly.”
- He said, “as soon as March and April hit, we definitely saw that the Eastern part of the country grow, that market is up a couple of hundred percent over last year.”
- Koenig said demand is coming from all over the country. If it’s East or West Coast, demand for tiny office sheds appears to be the next big trend in white-collar America as remote working trends continue to reshape everything we know about the economy.
- Readers may recall remote working has triggered one of the biggest outbound migration trends of cities to suburbs in decades, fewer vehicle miles are being driven, and commercial real estate implodes.
G. Back To School!?
1. Vanishingly small risk of death or severe illness for children from Covid
- The risk of severe illness and death to children from C19 is vanishingly small, according to the biggest study yet of those admitted to hospital, which the researchers say should reassure parents as they return to school.
- The study included two-thirds of all patients admitted to hospitals across England, Scotland and Wales with C19. Of these, 651 – less than 1% – were children and young people under 19. Six of these patients – less than 1% – died. All had severe underlying health conditions.
- “They were children with profound co-morbidities – not a touch of asthma and not cystic fibrosis,” said Calum Semple, professor in child health and outbreak medicine at the University of Liverpool, and co-lead of the study by the International Severe Acute Respiratory and emerging Infection Consortium. Their conditions included cancer and serious neurological, blood or heart issues.
- Co-author of the paper published in the BMJ, Dr Olivia Swann, clinical lecturer in paediatric infectious diseases at the University of Edinburgh, said: “The absolute risk of being admitted to hospital is tiny.” The risk of severe disease and death was also very small.
- But among those children who were admitted to critical care, they found those under the age of one were at three times the usual risk, although that included premature babies born and diagnosed in the hospital.
- Also at two to three times higher risk of ending up in critical care were black children. “The issues around ethnicity are very complicated,” said Semple. “They are issues which can partly be explained by deprivation. Some are explained by exposure in the community.”
- There were also underlying conditions, such as high blood pressure, which are more prevalent in black people, he said. But black children who were completely healthy were at no extra risk, said Semple. The message to the mother of a black child in Brixton or Glasgow was “they are safe to go back to school”, he said.
- Children with obesity were at higher risk. So were children in the 10-14 age bracket, who were the ones more likely to suffer from multisystem inflammatory syndrome, a new condition thought to be linked to C19.
- The researchers said they have identified symptoms that should help doctors diagnose the syndrome and they hope will lead to an expansion of the World Health Organization definition of it. These were a rash, conjunctivitis, abdominal pain, vomiting, and a low blood platelet count. “The skin, gut and whole child’s body is quite inflamed,” said Swann.
- Semple said parents should be reassured that their children would not be at harm from returning to school. He and Swann were both sending children back in September. Among children, “severe disease and death is vanishingly rare”, he said.
2. Researchers at the University of Arizona say they stopped a coronavirus outbreak before it spread by testing students’ poop
- Researchers at the University of Arizona say they may have prevented a coronavirus outbreak on campus by using wastewater analysis to track down students with C19.
- Wastewater-based epidemiology relies on measuring viral particles in sewage to assess the health of a community.
- The university began in-person classes on Monday. Before students arrived, Pepper and his team set up a system to test the wastewater coming from about 20 buildings on campus, including dorms.
- By Tuesday, the researcher’s wastewater-testing system had delivered troubling news: It detected elevated levels of coronavirus in campus sewage, stemming from one dorm in particular.
- The following day, the team tested the 311 individuals living in that dorm. Two tested positive; both were asymptomatic. Those two students were quarantined, and now the campus is conducting contact tracing to find any additional cases.
- The scientists hope other campuses and communities might be able to use the technique to contain outbreaks.
3. An Illinois school radically revolutionized large-scale COVID testing
- For the past decade, university arms races have centered on who can build the most luxurious dorms and biggest sports facilities or offer the most “country club” amenities like posh gyms and pools. But the University of Illinois at Urbana-Champaign may have cornered what has become the most crucial amenity of all as the 2020 school year kicks off: COVID testing.
- After receiving FDA emergency use authorization for its saliva test shortly before classes were scheduled to begin, the university—located about two hours south of Chicago—has implemented one of the most aggressive and comprehensive COVID testing and tracking programs in the nation, and is offering a hybrid model of in-person and virtual classes. “We don’t like this virus. We want to crush it, and that’s what we’re doing, and we’re doing it on a massive scale,” university president Timothy Killeen told CNBC on Friday.
- The testing is so widespread on campus that UIUC tests represented 20% of all tests administered in the state of Illinois and 1.5% of all tests administered nationwide, according to a recent column in the Chicago Sun-Times by Sheldon H. Jacobson, a professor of computer science at the University of Illinois at Urbana-Champaign and Janet A. Jokela, a dean at the University of Illinois College of Medicine at Urbana-Champaign.
- As the authors wrote, the approach too many other educational institutions are taking has a fatal flaw: “Many schools are testing students only upon their arrival to campus, and one week later. Then they are waiting for students to show symptoms before they test again. This strategy is a formula for disaster, given that a majority of infected students will be asymptomatic or display only mild symptoms.” The authors go on to say that a modest positivity rate of 2% of individuals arriving on campus will result in 500 to 900 initial infections. If those cases aren’t swiftly caught and the individuals quarantined, the virus will spread unfettered.
- Universities such as UNC–Chapel Hill, Michigan State, and Notre Dame have already canceled or temporarily halted in-person classes after experiencing such community spread. Others such as Stanford and Harvard elected to cancel in-person classes entirely.
How UIUC’s testing works
- Here’s how the UIUC system is set up. Each person who comes to campus gets an initial test, then must get tested twice a week. A negative test result within the past four days is linked to your ID via a university-developed tracking app, and without that green light you won’t be admitted to university buildings.
- A key component of UIUC protocol is its saliva-based test, which was developed in-house and is similar to one developed at Yale. As researchers at Yale outlined, nasal swab tests have several disadvantages, notably that the swabs can be in short supply, testing requires health care workers to use lots of PPE, and there are also shortages of the special chemicals needed for processing. Those factors make testing expensive and mean tests can take days to process: “Meanwhile, if patients don’t quarantine while awaiting test results that turn out to be positive, infection can continue to spread,” the Yale authors wrote.
- In contrast, the UIUC website says that typical saliva test results are available within five hours. A map of on-campus testing centers shows 17 locations, something of a miracle to any city- or suburb-dweller who has had to travel miles—or even to another state—to find an available COVID test.
- The university also updates and publicizes its own COVID tracking website. University spokeswoman Robin Kaler told the Chicago Tribune that on Tuesday, 120 positive results were identified from 15,850 new tests. The rolling five-day positivity rate is 0.75%, according to the latest data.
- To be sure, UIUC’s efforts are in their early stages. And the success or failure of its in-person learning plan will depend on student compliance when it comes to testing, as well as quarantining. But if there is a viable pre-vaccine path forward for in-person learning, this is one arms race that UIUC seems to be winning.
H. Practical Tips & Other Useful Information
1. Exercise May Boost Your Vaccine Response
- If you are an athlete, you may gain greater immunity from a flu shot than people who are less active, according to two complementary and timely new studies of exercise and vaccinations. The two studies, which involved the same group of elite runners, swimmers, wrestlers, cyclists and other athletes, suggest that intense training amplifies our vaccine response, a finding with particular relevance now, as the flu season looms and scientists work to develop a C19 vaccine.
- Having an immune system primed to clobber infections and respond robustly to vaccinations is obviously desirable now, during the ongoing pandemic. And in general, exercise aids immunity, most science shows. People who work out often and moderately tend to catch fewer colds and other viruses than sedentary people. More immediately, if you exercise your arm in the hours before a flu shot, you likely will develop a stronger antibody response than if you rest that arm, a few small studies indicate.
- But there have also been suggestions that under certain circumstances, exercise may dampen the immune response. Some epidemiological research and personal stories from athletes hint that intense, exhausting exercise might be detrimental to immunity in the short term. Marathon racers, for example, report catching colds at disproportionately high rates soon after a race, although some physiologists suspect these post-race respiratory problems are inflammatory, not infectious.
- The upshot, though, is that many questions have remained unanswered about whether and how strenuous workouts affect immunity and our bodies’ ability to respond favorably to a vaccination, such as the seasonal flu shot.
- So, for the new studies, scientists from Saarland University in Germany and other institutions decided to convince a large group of competitive athletes to get vaccinated, an effort more difficult than most of us might expect. In surveys, elite athletes tend to report relatively low rates of vaccination for the flu and other conditions, since many worry the shot will cause side effects that affect their training.
- But the researchers managed to recruit 45 fit, young, elite athletes, male and female. Their sports ranged from endurance events, like the marathon, to power sports, including wrestling and hammer throw, to team sports, such as basketball and badminton. All of the volunteers were in the middle of their competitive seasons during the studies.
- For the first of the two experiments involving these athletes, which was published in January in Brain, Behavior, and Immunity, the researchers hoped to establish whether being an athlete and having an athlete’s outsized fitness would goose or impede the young people’s immune reaction to a flu shot. So, the scientists also recruited an additional 25 young people who were healthy but not athletes to serve as a control group. They drew blood from everyone.
- Afterward, all of the young people received a flu shot and kept notes about any side effects they felt, such as a sore arm. The groups returned to the lab for follow-up blood draws a week, two weeks and six months after the vaccination. Then the researchers checked their blood for anti-influenza immune cells and antibodies.
- They found significantly more of those cells in the athletes’ blood, especially in the week after the shot, when everyone’s cellular reactions peaked. The athletes showed a “more pronounced immune response,” with presumably better protection against flu infection than the other young people, says Martina Sester, an immunologist at Saarland University and study co-author.
- The researchers speculate that the athletes’ immune systems had been strengthened and fine-tuned by the daily physical demands and damages of training, allowing them to respond so effectively to the vaccine.
- But those results, while notable, did not look at the acute effects of exercise and whether a single, intense workout might alter the body’s reactions to a vaccine, for better or worse. So, for the second of the new studies, which was published in July in Medicine & Science in Sports & Exercise, the scientists returned to the same data, but focused now only on the immune reactions of the athletes.
- They compared the numbers of immune cells and antibodies in those athletes who happened to have gotten their flu shot within two hours of their most recent training session against those of athletes whose shot had come a day after their last workout. If intense training blunted immune reactions, then the first group of athletes would be expected to show fewer new immune cells than those who had gotten their shot after a longer rest.
- But the researchers found no differences. Whether the athletes’ inoculations came almost immediately after training or a day later, their immune reactions were the same. A strenuous workout beforehand had not lowered — or boosted — the response.
- Together, the two studies tell us that being in shape is likely to increase our protection from a vaccination, no matter how intensely or when we work out before the shot, Dr. Sester says.
- Of course, these studies focused on elite, competitive athletes, which most of us are not. But Dr. Sester believes even more-casual recreational athletes are likely to mount better flu-vaccine responses than sedentary people. Likewise, she and her colleagues expect high fitness should improve immune responses to other vaccines, including, potentially, a C19 shot.
- “The basic principles of vaccine response are probably the same,” she says. Future studies will have to confirm that possibility, though, if and when a vaccine becomes available.
K. Johns Hopkins COVID-19 Update
August 28, 2020
1. US Numbers & Trends
- The US CDC removed its previous C19 reporting page and transitioned to its COVID Data Tracker dashboard. The dashboard provides links to a variety of data, including incidence and mortality, laboratory testing, community impact (eg, mobility), and high-risk populations (e.g., healthcare workers, incarcerated populations). Some of the data is available at the state and county level directly through the dashboard. The dashboard added a 7-day moving average for daily deaths, and it once again reports C19 data from New York City and New York state separately.
- The CDC reported 5.80 million total cases (46,393 new) and 178,998 deaths (1,239 new). In total, 19 states (no change) are reporting more than 100,000 cases, including California and Florida with more than 600,000 cases; Texas with more than 500,000; New York with more than 400,000; and Georgia and Illinois with more than 200,000. We expect Arizona to surpass 200,000 total cases in the coming days. Notably, the US fell out of the global top 10 in terms of per capita daily incidence.
- Several US territories continue to report extremely high per capita daily incidence. Guam is reporting 446 new daily cases per million population, which would be #1 globally—more than 75% greater than the Maldives, the actual #1. It previously appeared as though much of Guam’s increased incidence was due to a large spike of 105 new cases reported on August 21; however, Guam has reported more than 50 new cases on 6 of the 7 days since then, including a new record high of 136 new cases on August 27. The US Virgin Islands is reporting 282 new daily cases per million population, which would also be #1 globally. Puerto Rico’s daily incidence has decreased over the past week or two, but it is still reporting 162 new daily cases per million population. This would put it at #10 globally, falling between Costa
2. South Korea
- South Korea continues to report a resurgence of C19, and it has experienced a range of disruptions and operational changes as a result of the increased transmission or response activities. The surge in incidence drove the Ministry of Health and Welfare to increase social distancing restrictions nationwide to Step 2 for a period of 2 weeks. On Thursday, proceedings of South Korea’s National Assembly were suspended in order to disinfect the building after a journalist tested positive for SARS-CoV-2. Additionally, the South Korean government ordered most schools in and around Seoul to close and transition classes online earlier this week. All students in the affected cities and provinces, with the exception of high school seniors, will participate in online classes through at least September 11. After delays and disruptions earlier in the year, South Korean schools reopened in late May and early June.
- Earlier this week, physicians across the country, including in Seoul, engaged in a 3-day strike organized by the Korean Medical Association. The walkout of thousands of doctors, primarily interns and resident doctors at hospitals, stems from their disapproval of recent government decisions to increase the number of medical students admitted to medical schools in the future and to open a new public medical school for the purpose of expanding access to healthcare services nationally. The government also aims to expand insurance coverage to more traditional medicines and practices and increase the availability of telemedicine.
- The doctors reportedly disapprove of these plans because they believe they would unfairly increase competition in an already-crowded job market. They argue that the funding for these efforts would be better spent to increase salaries for trainees, which could enable them to move to rural areas that are experiencing a shortage of doctors. The strike has led to disruptions in hospital operations, leading facilities to reduce operating hours, cancel appointments, and delay procedures. South Korean Minister of Health Dr. Park Neung-hoo ordered protesting doctors to return to work, threatening those who do not comply with the possibility of suspending or revoking their licenses, fines of up to US$25,000, or up to 3 years in prison. To date, the government does not appear to have taken punitive action against striking doctors.
3. European Schools
- Like most of the rest of the world, European countries have been debating whether to reopen schools and how to best protect students and teachers. Public Health England conducted enhanced surveillance among schools that reopened between June 1-July 31 in order to provide better information regarding SARS-CoV-2 transmission risk in school settings. While approximately 80% of schools remained open in some capacity during the UK lockdown to support certain priority groups (eg, children of healthcare workers), the vast majority of children did not attend in-person classes. In June, the number of students attending schools increased from 475,000 to more than 1.6 million. The researchers identified 198 total C19 cases over the study period, including 121 linked to 30 different outbreaks and 67 individual cases (ie, not linked to transmission in schools). An additional 10 cases were reported as “co-primary” cases, which were detected at the same time and had a common epidemiological link (e.g., to a parent). Of these cases, 70 were students, and 128 were staff members.
- The study found a strong correlation between C19 incidence in the region and the number of outbreaks in schools. The authors concluded that schools were associated with relatively few C19 outbreaks after the easing of the lockdown, and the outbreaks that did occur were more likely to involve staff members. As a result of the correlation between school-based outbreaks and community transmission, the researchers emphasized the importance of community-based risk mitigation measures (eg, mask use, physical and social distancing). While the study provides evidence that schools do not drive transmission, Dr. Shamez Ladhani, one of the study’s authors, noted that the results reflect only data that were gathered right after the lockdown ended. Class sizes were very small at the time, and school-based transmission principally affected adult staff.
- While it is possible that schools are not major drivers of transmission, Dr. Hans Kluge, the WHO Regional Director for Europe, stated that there is increasing evidence of children infecting others at social gatherings and that incidence among young people is increasing. The WHO recently advised that children 12 years and older should wear a mask under the same conditions as adults in order to mitigate transmission risk. As winter approaches in the Northern Hemisphere, there are concerns that increased close contact between children and more vulnerable older adults could lead to a rise in incidence and deaths.
- In Germany, schools are beginning to reopen, with the majority of students returning for in-person classes. To mitigate transmission risk, German schools are reportedly focusing on improved ventilation and cohorting students (ie, keeping classes separate). The decision to bring all students back at once hinged partly on the number of available teachers, which did not support efforts to split students into smaller groups. Interestingly, masks are required on most school grounds in Germany, but not necessarily in classrooms in order to help students concentrate.
- On Wednesday, Kenyan President Uhuru Kenyatta announced that Kenya is extending its current social distancing restrictions for 30 days. Kenya’s C19 epidemic peaked in early August, at approximately 675 new cases per day, and it is now less than half of that (286 new cases per day) and still decreasing. In early July, despite several months of steadily increasing daily incidence, Kenya relaxed a number of social distancing measures in order to enable its economy to recover. Three (3) weeks later, however, President Kenyatta was forced to re-institute more restrictive measures to combat Kenya’s rapidly growing epidemic. He urged Kenyans to be vigilant in complying with the recommended actions, noting that they must all hold themselves and others accountable.
- The effort was successful in turning the tide against the C19 epidemic, and in his most recent address, President Kenyatta applauded Kenyans’ efforts. He also continued to emphasize their personal responsibility and duty to protect others, “a happy debt to pay [their] fellow citizens.” While Kenya made considerable progress since the measures were implemented a month ago, he noted that much uncertainty remains about the future trajectory of the epidemic, encouraging Kenyans not to be complacent.
- While some restrictions will remain intact, such as the nationwide 9pm-4am curfew, others will be relaxed to some degree. Bars and nightclubs will remain closed, but hotels will be permitted to serve alcohol. Additionally, the Ministry of Health will coordinate with bar owners to develop “self-regulating mechanisms” over the next 30 days with the aim of allowing them to resume operations. Restaurant hours of operation will still be restricted, but they will be permitted to extend closing by 1 hour, from 7pm to 8pm. Additionally, the limit on the attendance at weddings and funerals will increase to 100 people, and the Ministries of Health and Sports, Culture, and Heritage are expected to issue guidance for resuming sporting events.
5. Wild Polio Elimination in Africa
- Earlier this week, the WHO announced that wild-type polio viruses have been eliminated from the continent of Africa, a major step toward eradication. Polio eradication programs, including vaccination campaigns, were suspended early in the C19 pandemic due to concerns that the programs would not be able to continue in-person, door-to-door efforts safely in the midst of the pandemic, particularly that these efforts could inadvertently spread C19 in vulnerable communities. Experts warned that scaling back eradication activities would inevitably result in polio outbreaks that could have lasting negative effects on eradication efforts. Polio vaccination programs began to resume in July, initially limited to outbreak response before expanding to include preventive campaigns.
- In addition to contributing toward eradication, lessons and capacities from polio have been critical to the C19 response in Africa. Over its history, polio eradication efforts have incorporated a myriad of other healthcare and public health benefits—including mosquito nets, vitamin A, and other vaccinations—and this approach is now being applied to the C19 response. Additionally, it is critical to establish trusted relationships with local leaders, which helps establish inroads with affected communities, implement culturally appropriate interventions, and build public confidence in the response efforts, including contact tracing and vaccination. The laboratory network and infrastructure established for polio is also being utilized for C19. The network includes 16 laboratories across 15 countries in Africa, and 50% of its capacity has been transitioned to support SARS-CoV-2 testing. Leveraging existing capacity and expertise, such as through polio eradication efforts, is critical to making efficient use of available resources.
6. China Schools Reopening
- China is expected to fully reopen schools next week. China has already opened schools for 75% of students, and this move will ultimately enable all students to resume in-person classes. China’s school systems include nearly 300 million teachers and students nationwide. According to China’s Ministry of Education, no cases of C19 have been detected at schools during the initial phases of resuming in-person classes, through the point of reaching 75% capacity. The Ministry of Education emphasized that conditions at schools across the country may vary and that schools cannot take a “one size fits all” approach to implementing appropriate C19 protective measures. It also emphasizes the importance of local control of C19 transmission, much like the US CDC emphasizes the need to account for risks associated with local community transmission as students resume in-person classes. Colleges and universities have been directed to strictly control access to campus, including checking identification for students and teachers and limiting visitors, in order to mitigate the risk of introducing SARS-CoV-2. While all schools will reportedly be open, it may still take time for all students to resume in-person classes. According to information published by the Ministry of Education, schools will phase in their students, and provincial plans could take as long as 37 days to reach 100% capacity. Including colleges and universities, the phase-in period is scheduled to continue into mid-October.
7. Rapid Antigen Test EUA
- The US FDA issued an Emergency Use Authorization (EUA) for a rapid antigen test developed by Abbott Laboratories that can return results in approximately 15 minutes. The test uses widely available testing equipment, as opposed to proprietary reagents or machines, and it can be performed on site at the point of care. A press release from Abbott indicates that the test has demonstrated reasonably high sensitivity (97.1%) and specificity (98.5%).
- Antigen tests detect the presence of viral particles, including specific proteins, whereas traditional PCR tests detect the presence of viral RNA. Antigen tests can be performed more quickly than PCR tests, but they tend to be less accurate. The test is projected to cost US$5 each, which could help make it more widely available, and it will have an accompanying smartphone application that will enable individuals to present documentation of recent negative tests. The US government finalized an agreement to purchase 150 million tests, at a cost of US$750 million. Widespread distribution of these tests would substantially increase national testing capacity, and rapid, on-site testing capability would dramatically decrease the delays in processing tests and return results that continue to plague PCR-based diagnostic tests.
- The test has been described by some, including US Assistant Secretary for Health Admiral Brett Giroir, as a “game changer”; however, there are some notable limitations that should be considered as well. The ability to use widely available testing equipment expands the number of laboratories that could perform the test, but the test still requires a laboratory and trained personnel to conduct it, as well as a nasopharyngeal swab to obtain the specimen. It is not a test that individuals can take at home. Additionally, the US$5 cost pertains only to the test, and the cost of personnel time and laboratory testing supplies and equipment will likely increase the overall cost. The test is also limited to symptomatic individuals, and as we have covered previously, asymptomatic or presymptomatic transmission is a major driver of the C19 pandemic. A number of other relatively inexpensive, rapid antigen tests are currently in development, including some that are designed for home use.
8. US CDC Testing Guidance
- Multiple reports indicate that the changes to the US CDC’s SARS-CoV-2 testing guidance—in particular, that asymptomatic individuals “do not necessarily need a test,” even if they have known exposure to a C19 case—were directed by senior US government leadership outside the CDC. The changes were reportedly made under pressure by senior officials at the Department of Health and Human Services and the White House coronavirus task force. Notably, several reports also indicate that Dr. Anthony Fauci was undergoing surgery at the time of these discussions and did not sign off on the changes. This conflicts directly with statements made by Admiral Brett Giroir, the Assistant Secretary for Health and the “coronavirus testing czar,” who stated that “all the doc[tors] signed off” on the new guidance and that the updates represent an “absolute consensus” by the US government’s top experts.
- Multiple experts have commented that these reports raise serious concerns that the changes may have been made on the basis of political pressure rather than available scientific evidence. President Donald Trump has repeatedly stated that he would like to see reduced testing in order to decrease the reported C19 incidence, which would likely have serious negative effects on the US response. Late Wednesday evening, CDC Director Dr. Robert Redfield issued a statement in support of the new guidance. In his statement, Dr. Redfield noted that “testing is meant to drive actions and achieve specific public health objectives”; however, it is unclear how health officials could effectively conduct actions such as contact tracing and notifying individuals who were exposed to asymptomatic infections if no testing is conducted.