October 19, 2020
Without reliable information, we rely on fear or luck.
“I long for the day when each and every day we see fewer cases than the day before. But if you were to ask me when that day would be, I don’t honestly know.”David Aronoff, director of the Division of Infectious Diseases at Vanderbilt University Medical Center in Nashville, Tennessee
“If we get back to 70,000 a day and we get beyond that, then the system probably is not really prepared to absorb those additional hospitalizations. And when you can’t provide adequate care, the death rates get worse.”Ryan Demmer, an epidemiologist and associate professor at the University of Minnesota
“Ultimately, I think that many Americans understand that everything that we have been through so far is just the leading edge of something much larger. Whether you want to call it ‘the big meltdown’, ‘the collapse of society’ or ‘the perfect storm’, the truth is that the party is ending.”Michael Synder, author and blogger
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
4. C19 Spread Across the US Since March 15
1. Will the C19 virus become endemic? (!) (*)
1. What to do about Halloween (*)
L. Linked Stories
4. Closing Borders and Stopping the C19 Virus: WHO & EU Were “Fatally Mistaken” (Countries with international travel restrictions suffered fewer C19 fatalities)
A. The Pandemic As Seen Through Headlines
(In no particular order)
- Remdesivir Fails to Prevent Covid-19 Deaths in Huge Trial
- Gilead Disputes WHO Data Confirming COVID-19 Drug Remdesivir Is A “Flop”
- Halted Trials Raise New Safety Questions About ‘Rushed’ COVID-19 Vaccines
- Pfizer Plans To Apply For FDA’s Emergency-Use Approval for Vaccine During Third Week Of November
- Hundreds of thousands of doses of COVID-19 vaccine roll off production line
- Gov. Cuomo lays out massive COVID-19 vaccination plan across New York
- HHS Secretary says COVID-19 vaccine, treatment may be ‘weeks away’
- Scientists worry as more Americans say they’ll refuse COVID-19 vaccine
- President Trump Says He Won’t Force Americans To Take COVID-19 Vaccine
- In the US, 50 States Could Mean 50 Vaccine Rollout Strategies
- The Trump administration said on Friday that it would contract with CVS and Walgreens pharmacies to provide free coronavirus vaccines to residents of long-term care centers, offering one of the first clues into how vaccines will be distributed
- WHO: Young and healthy may have to wait until 2022 for a covid-19 vaccine
- Britain moves closer to COVID-19 vaccine trials that infect volunteers
- A city in eastern China has begun inoculating some people against the coronavirus with a vaccine that has not completed late-stage clinical trials, ignoring warnings from scientists that the campaign could carry major health risks
- NIH tests therapies to help cut hospital stays for COVID-19 patients
- As covid-19 cases surge, global study paints grim picture for elder-care homes
- We cannot rely on magical thinking: Herd immunity is not a plan
- Top Pandemic Doctor Explains Hong Kong’s Low Covid-19 Fatality Rate: early, aggressive hospitalization and treatment
- Exhaustion and impatience are creating new risks as coronavirus cases soar in parts of the world
- US reports most new cases since late July
- Europe adds 200,000 new cases in a day
- Europe surpasses US in new daily cases of COVID although they test less only half as much
- Global coronavirus cases rise by one-day record of 400,000 on Friday
- Kansas City may become ‘next New York’ amid COVID-19 surge: doctor
- Italy reports record 11,000+ new cases
- Italy prepares tightest restrictions since lockdown ended as Europe outbreak intensifies
- Italy ready to close bars, restaurants for first time since lockdown ended
- Russia reports 15,000k+ new cases again
- Poland reports 8,000+ new cases
- France reports new record number of new cases
- Ireland weighs return to lockdown
- Chancellor Merkel Urges Germans to Reduce Contacts and Travel as Infections Rise
- Dense living quarters in Israel make their communities hotbeds of the virus
- A protest against the Czech Republic’s newest restrictions, including a ban on sports events, turns violent
- Indonesia, where coronavirus cases have been rising steadily for months, now leads Southeast Asia in the number of reported cases and deaths
- China links virus on frozen food packaging to an outbreak, but evidence for such transmission is scant
- Under rules starting today in Scotland, masks will be required in workplaces and cafeterias. But couples who marry or enter into civil partnerships will no longer be required to wear face masks during the ceremony
- New York is shifting its strategy for combating the coronavirus, targeting small infected areas for restrictions rather than by larger regions or counties
- Months into COVID-19 pandemic, Iran sees worst wave of virus deaths
- Why Are So Many Americans Suddenly Relocating, Buying Guns, & Storing-Up Huge Quantities Of Food?
- 246,000 people living in NYC filed a change of address request – that is an almost 100% increase compared to the same time period in 2019
- Greenwich Housing Market Just Had Its Best Quarter In A Decade Thanks To The Coronavirus
- So many Americans are stockpiling food that it has actually caused a very serious shortage of Mason jars
- 40% of renters can’t afford essentials as a result of COVID-19
- The Lombardy region of Italy launches the first investigative COVID-19 commission
- A Canadian spin studio followed public health guidelines, but 61 people still caught the coronavirus
- Hong Kong Sees “Alarming Rise” In Suicide And Depression Among Young People
- Fall Enrollment Slides As Coronavirus Threatens Higher-Education Bubble
- Casket outside Brooklyn nursing home filled with 6,500 covers of Cuomo’s book
- UK College Orders COVID-Carrying Students To Wait In Room, ‘Let Others Out First’ If Fire Breaks Out
- Michigan woman finally goes home after 196 days in hospital with COVID-19
- Doctors find signs of recovery in some Covid-19 patients with severe lung damage
- The U.S. Is Headed for a COVID-19 Baby Bust
- Delta Air Lines will stop blocking middle seats in first half of 2021
- Texas eight grade girl wins $25,000 for developing potential COVID-19 treatment
- NY Gov. Cuomo announces New York movie theaters to reopen, but not in NYC
- New York will allow ski resorts to reopen at reduced capacity
- Dr. Fauci Tells Americans To “Bite The Bullet And Sacrifice” Thanksgiving
- Sole 2 residents of tiny Italian town insist on masks and social distancing
- Singapore Airlines Transforms Grounded Planes Into Pop-Up Restaurants
- UK Bans Sex For At-Risk Couples
- Quarantine TV Shows Are Here, and They’re Painful
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 40,264,219
- New Cases = 324,927
- New Cases (7 day average) = 353,034 (+4,077) (+1.2%)
- 7 day average of new cases is a record high
US Cases & Testing:
- Total Cases = 8,387,799
- New Cases = 44,941
- New Cases (7 day average) = 56,322 (+404) (+0.7%)
- Percentage of New Global Cases (7 day average) = 16.4%
- Total Number of Tests = 125,683,881
- Percentage of positive tests (7 day average) = 6.2%
- 7 day average of new cases has been rising rapidly since 9/13
- Since 9/11, the 7 day average of new cases has increased from 36,054 to 56,322, an increase of 20,268 new cases (an increase of 56.2%)
- 7 day average of percentage of positive tests has increased from 5.1% to 6.2% since 10/4
- Significant increases in the 7 day average of new cases and 7 day average of percentage of positive tests may foreshadow increases in the number of deaths
Europe Cases (10/16)
- Total Cases = 7,010,652
- New Cases = 137,176
- New case in Europe on 10/16 were nearly double new cases in US on same day
- Total cases in Europe are 84.6% of total US cases
- Total Deaths = 1,118,167
- New Deaths = 3,971
- New Deaths (7 day average) = 5,241 (+3) (+0.1%)
- Since 9/9, the 7 day average of new deaths has remained within a narrow range from a low of 4,957 to a high of 5,335, a range of 7.6%
- 7 day average of new deaths has been relatively stable since 9/9 even though the 7 day average of new cases has been rapidly rising (the 7 day average of new cases has risen 32.9% since 9/9)
- 7 day average is 25.9% less than peak of 7,075 on 4/18
- Total Deaths = 224,730
- New Deaths = 448
- New Deaths (7 day average) = 723 (+16) (+2.3%)
- Percentage of Global New Deaths (7 day average) = 18.2%
- Since 9/22, the 7 day average of new deaths has remained within a narrow range from a low of of 702 on 10/18 to a high of 760 on 9/26, a range of 7.6%
Europe Deaths (10/6):
- Total deaths = 246,828
- New deaths = 1,194
- Total deaths in Europe on 10/16 exceed total deaths in US on same day by 23,184, or 9.4%
- New deaths in Europe on 10/16 exceed new deaths in US on same day by 266, or 22.3%
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (10/18)
- The overall 7-day average positivity rate in the US has increased to 6.2%, up from 5.1% on 10/4. Hospitalizations in the US have increased nearly 22% over the last two weeks. There are currently 36,248 patients hospitalized in the US with C19. Of note on a state level:
- North Dakota 7-day average positivity rate reached an all-time high of 40.9%. On 10/18, there were 717 new cases of C19, up from 416 new cases on 10/4. ND Hospitalizations have nearly doubled over the last two weeks increasing from 100 to 210 hospitalized patients
- New Jersey has the biggest positivity rate change over the past two weeks, increasing 7.25x from 1.2% on 10/4 to 8.7%. NJ Hospitalizations have increased nearly 52% over the same period
4. C19 Spread Across the US Since March 15
5. Deaths are not keeping pace with the sharply rising case counts in Europe and the US — yet
- In both Europe and the United States, coronavirus cases are mounting sharply for a third time in the pandemic, but reported deaths are not rising proportionately.
- Part of the reason may be more widespread testing. Jon Zelner, an epidemiologist at the University of Michigan, said that many of the additional cases are probably being found among younger people who have no symptoms or mild illness — cases that might have gone undetected before. That is what is happening in Michigan, he said in an interview.
- But he said that it also may just be a matter of time. “Deaths are a very laggy indicator of transmission,” he said, and the deaths occurring now are largely among people who became ill 30 to 40 days ago. Dr. Zelner said he expected the current surge in cases to be reflected in an increase in deaths in November.
- Single-day and weekly records for new cases are growing more common both in European countries and in individual American states.
- In the U.S., average daily reported cases have increased by 28% over the last 14 days, and hospitalizations are rising, while deaths have increased 1 percent.
- Ohio, Indiana, North Dakota, Illinois, New Mexico, Wyoming, Colorado, South Dakota, Kentucky, West Virginia and Idaho each reported more cases this week than in any previous seven-day period. So did Minnesota, even though the state reported no new cases on Saturday because of computer updates.
- Only one of those states — North Dakota — was among the eight reporting the highest number of deaths relative to their populations.
- In France, which reported 115,897 cases and 619 deaths in the last week, according to a Times database, curfews were imposed in Paris and other cities. Italy reported a record of 10,925 new infections on Saturday, almost three times the number it was averaging 14 days ago, and a slight increase of 47 deaths. The government is expected to announce further restrictions on Sunday.
- Poland also reached a new high, with 9,622 new infections on Saturday and 84 coronavirus-related deaths, according to the Health Ministry. And Ukraine, which has extended a lockdown until the end of the year, reported two daily records of 6,410 new infections and 109 deaths on Saturday according to its National Security and Defense Council.
- The European region registered its highest weekly incidence of cases since the pandemic’s beginning, the World Health Organization said on Thursday. “Daily numbers of cases are up, hospital admissions are up, C19 is now the fifth leading cause of death and the bar of 1,000 deaths per day has now been reached,” said a statement by Dr. Hans Kluge, the organization’s regional director for Europe. Still, deaths were still five times fewer than the April peak.
6. Why C19 Is Spreading Again: Fatigue, Colder Weather, Eased Restrictions
- New coronavirus cases hit their highest level since mid-August on Wednesday, a sign of a fall surge predicted by public-health officials.
- For the eighth time since October began, newly reported cases nationally ticked above 50,000, fueled by simmering outbreaks in every region of the country.
- For the past week, the seven-day average of new cases was outpacing the 14-day average in more than 40 states and Washington, D.C., according to a Wall Street Journal analysis of Johns Hopkins University figures. When the seven-day average is higher than the 14-day average, it suggests cases are rising.
- Hospitalizations also have swelled across the U.S. in recent weeks, though deaths haven’t yet surged. Deaths often lag behind new cases and hospitalizations, given the duration of the disease. The seven-day average of daily deaths attributed to Covid-19 has been hovering around 700 for about three weeks, down from around 1,000 two months ago.
- The U.S. has more fatalities than any other country in the world—more than 217,600 since the pandemic began. But it doesn’t have the highest percentage of cases that are fatal. About 2.7% of reported cases in the U.S. have been fatal, according to data from Johns Hopkins. That figure has declined in recent months as treatments have improved and testing has expanded, allowing more mild and asymptomatic cases to be detected. Since the summer, younger people have made up a growing share of new U.S. cases.
- The virus has spread to more rural counties and other communities, exposing vulnerable populations that hadn’t yet experienced it significantly and who are now reacting instead of taking steps to prevent the virus, public-health researchers said.
- Some people have grown tired of restrictions on their movements and might be taking more risks than they did in the spring, they said. Mixed and inconsistent messaging from federal and local officials over preventive measures has sowed confusion and complacency. Some local governments have eased restrictions on businesses and requirements to wear masks. Meanwhile, college students returned to campuses, leading to some spreading of the virus, and the onset of cooler weather has led many Americans indoors, where the virus is more transmittable, the public-health researchers said.
- But the researchers also said it is difficult—and might be too early—to identify the exact causes of the recent increase in cases.
- “I long for the day when each and every day we see fewer cases than the day before,” said David Aronoff, director of the Division of Infectious Diseases at Vanderbilt University Medical Center in Nashville, Tenn. “But if you were to ask me when that day would be, I don’t honestly know.”
- Since Oct. 1, an average of nearly 49,000 cases has been reported each day, a marked increase from the previous six weeks, when the average hovered below 41,000.
- Daily case-count tallies are likely to increase or remain at high levels without concerted use of such strategies as enhanced testing, widespread mask-wearing and clear, consistent messaging, epidemiologists and public-health researchers said.
- “It doesn’t have to be this way,” said Jewel Mullen, the associate dean for health equity at the Dell Medical School at the University of Texas at Austin. “The longer it takes for us to adopt behaviors to lower collective risk, the longer it’s going to take for us to recover socially, economically from a pandemic standpoint.”
- New case counts are high nationally, but it is far from uniform across the country; often one area surges when another improves. While cases have ebbed in Sunbelt states like Arizona, they have gone up throughout parts of the rest of the country, especially the upper Midwest. And community transmission has persisted in states like Florida and Texas where cases have dropped recently.
- “It’s almost like we never ended the first wave,” said Marissa Levine, a professor at the University of South Florida College of Public Health. “We may be going into the third hump of the first wave.”
- On a national scale, the U.S. never saw the same substantial drops in cases experienced in European countries before infections rose there again.
- The U.S. Centers for Disease Control and Prevention said in a recent report that divisiveness and mixed messages over mask-wearing might have contributed to a rise in coronavirus cases among younger people in a Wisconsin county. Another CDC report found increases in positivity rates among older age groups followed surges in younger populations. This week, a judge upheld Gov. Tony Evers’s mask mandate and public-health emergency after three residents challenged the actions.
- Without a vaccine or a therapeutic breakthrough, prevention tools are the best approach for controlling the spread. Precautions like wearing masks and maintaining distance help lower risk of transmission but don’t entirely eliminate it, especially without full compliance, according to health officials.
- “We have been saying it for months now that if everybody doesn’t do it, we’re not going to have this huge, overwhelming success,” said Jasmine Marcelin, an assistant professor at the University of Nebraska Medical Center and infectious-diseases physician. “It’ll be in fits and starts.” Communities might continue to slide back and forth between phases of the pandemic, Dr. Marcelin warned.
- Compliance fatigue has been seen as a contributing factor to the second wave of infections that has spread across Europe in recent weeks. Across the Continent, restrictions are snapping back into place as cases rise and hospitals once again fill up.
- In the U.S., swelling cases have already spurred record-high hospitalizations in states including Wisconsin, the Dakotas, Montana and Utah. The U.S. recorded the highest number of patients hospitalized with Covid-19 since the end of August on Wednesday, according to data from the Covid Tracking Project.
- More deaths and hospitalizations are likely to follow as cases edge higher and potentially shift from younger people to more vulnerable populations, a situation that is already playing out in Europe. The latest projections from the University of Washington’s Institute for Health Metrics and Evaluation indicate that nearly 180,000 additional deaths could occur in the U.S. by Feb. 1.
- Health-care professionals are able to provide better care when not overwhelmed with patients or short on critical supplies, said Ryan Demmer, an epidemiologist and associate professor at the University of Minnesota.
- “If we get back to 70,000 a day and we get beyond that, then the system probably is not really prepared to absorb those additional hospitalizations,” he said. “And then when you can’t provide adequate care, the death rates get worse.”
- Epidemiologists and public-health leaders have continued to urge Americans to stay vigilant to avoid this outcome.
- Seven months into the pandemic, Dr. Aronoff of Vanderbilt has found himself often thinking of Sisyphus, the Greek mythological figure known for his eternal plight.
- “Every day since March, I come to work, and I push up against this boulder of Covid-19, and at the end of the day I feel like I may have accomplished something,” said Dr. Aronoff. “Then I come back in the morning, and I see the boulder at the bottom of the mountain again.”
7. Europe’s 2nd Wave — The Numbers in Context
- The summer months have been kind to most European countries, with coronavirus fatalities falling substantially across all of the major European economies during June, July & August. Unfortunately, in the last few weeks cases — and now deaths — have begun to rise in many European countries.
The “second wave” in context
- Although deaths have begun rising, so far this second European wave is still much smaller than the first. Even in Spain, France and the UK, which are seeing some of the bigger second waves, weekly deaths are still down more than 90% relative to the peaks seen back in late March and early April.
- Similar charts of confirmed cases on the other hand look a lot scarier, with Europe as a whole averaging more than 100,000 new confirmed infections per day over the last week. The difference between deaths and cases is partly explained by a significant increase in testing, partly explained by the lag between positive tests and fatalities and partly explained by lower death rates (possibly due to younger patients or marginally better COVID treatments).
- European leaders are already taking the rise in infections seriously. France has imposed a curfew in Paris and other major cities, London has been upgraded to the UK’s “tier 2” level of restriction, Spain has implemented an emergency lockdown in Madrid and Germany has just announced a new raft of measures to limit public gatherings. Sweden, meanwhile, continues to plot its own path with its light-touch approach to restrictions having never closed schools, shops, restaurants or gyms throughout the entire pandemic.
C. New Scientific Findings & Research
1. Antibodies Fade Quickly in Recovering C19 Patients
- In the absence of approved, effective treatments for C19, some hospitals have been treating patients with severe COVID symptoms with blood plasma from recovering patients. The blood of recovered patients contains antibodies that act against the coronavirus. While plasma hasn’t yet shown a benefit in randomized trials, some small retrospective studies suggest it may reduce illness severity and reduce hospitalization time.
- This week in mBio, an open-access journal of the American Society for Microbiology, researchers report that antibody levels in the blood of C19 patients drop rapidly during the weeks after their bodies have cleared the virus and symptoms have subsided. If convalescent plasma is ultimately shown to have a clear benefit, the authors concluded, then it needs to be collected during a specific window of time after recovery. However, recovering patients can’t donate blood until at least 14 days after symptoms have subsided, to give the body time to clear viral particles.
- “We don’t want to transfuse the virus, just transfuse the antibodies,” said Andrés Finzi, Ph.D., at the University of Montreal, in Canada. “But at the same time, our work shows that the capacity of the plasma to neutralize viral particles is going down during those first weeks.”
- The spike protein of the coronavirus (SARS-CoV-2) plays a crucial role in helping the virus grab and invade host cells. Antibodies produced by the body’s immune system bind to a part of this protein and block the capacity of this “key” to engage with the host’s cellular “lock”, said Finzi, preventing the viral particle from infecting a cell host.
- Previous studies suggest that antibodies against the SARS-CoV-2 spike protein peak 2 or 3 weeks after the onset of symptoms. Findings from an earlier cross-sectional study by Finzi’s group, involving more than 100 patients, suggested that the ability of plasma to neutralize the virus decreased significantly between 3 and 6 weeks after symptom onset.
- In the new longitudinal study, Finzi and his colleagues analyzed blood samples collected at one-month intervals from 31 individuals recovering from C19. They measured levels of immunoglobulins that act against the coronavirus S protein and tested the ability of the antibodies to neutralize the virus.
- The researchers observed variation on the level of individual patients but identified a consistent overall signal: The levels of Immunoglobulins G, A, and M that target the binding site decreased between 6 and 10 weeks after symptoms began. During the same time period, the ability of the antibodies to neutralize the virus similarly fell.
- Finzi’s group has continued to study blood samples from the patients. Understanding how the levels of antibodies change over time, he said, is critical not only for optimizing the use of convalescent plasma but also for understanding vaccine efficacy and whether or not previously infected people are at risk of re-infection.
- “How long do antibodies protect you?” he asked.
- Finzi’s other research focuses on the immune response to human immunodeficiency virus, or HIV, which differs dramatically from SARS-CoV-2.
2. Johns Hopkins Researchers Identify Immune System Pathway That May Stop C19 Infection
- While the world waits eagerly for a safe and effective vaccine to prevent infections from the coronavirus (SARS-CoV-2), researchers also are focusing on better understanding how SARS-CoV-2 attacks the body in the search for other means of stopping its devastating impact. The key to one possibility — blocking a protein that enables the virus to turn the immune system against healthy cells — has been identified in a recent study by a team of Johns Hopkins Medicine researchers.
- Based on their findings, the researchers believe that inhibiting the protein, known as factor D, also will curtail the potentially deadly inflammatory reactions that many patients have to the virus.
- Making the discovery even more exciting is that there may already be drugs in development and testing for other diseases that can do the required blocking.
- The study was published recently in the journal Blood.
- Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus — making the pathogen look like the spiny ball from a medieval mace — are the means by which it attaches to cells targeted for infection. To do this, the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surface of cells in the lungs, blood vessels and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell.
- The Johns Hopkins Medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents factor H from using the sugar molecule to bind with cells. Factor H’s normal function is to regulate the chemical signals that trigger inflammation and keep the immune system from harming healthy cells. Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defense mechanism nature intended to safeguard them.
- “Previous research has suggested that along with tying up heparan sulfate, SARS-CoV-2 activates a cascading series of biological reactions — what we call the alternative pathway of complement, or APC — that can lead to inflammation and cell destruction if misdirected by the immune system at healthy organs,” says study senior author Robert Brodsky, M.D., director of the hematology division at the Johns Hopkins University School of Medicine. “The goal of our study was to discover how the virus activates this pathway and to find a way to inhibit it before the damage happens.”
- The APC is one of three chain reaction processes involving the splitting and combining of more than 20 different proteins — known as complement proteins — that usually gets activated when bacteria or viruses invade the body. The end product of this complement cascade, a structure called membrane attack complex (MAC), forms on the surface of the invader and causes its destruction, either by creating holes in bacterial membranes or disrupting a virus’ outer envelope. However, MACs also can arise on the membranes of healthy cells. Fortunately, humans have a number of complement proteins, including factor H, that regulate the APC, keep it in check and therefore, protect normal cells from damage by MACs.
- In a series of experiments, Brodsky and his colleagues used normal human blood serum and three subunits of the SARS-CoV-2 spike protein to discover exactly how the virus activates the APC, hijacks the immune system and endangers normal cells. They discovered that two of the subunits, called S1 and S2, are the components that bind the virus to heparan sulfate — setting off the APC cascade and blocking factor H from connecting with the sugar — and in turn, disabling the complement regulation by which factor H deters a misdirected immune response.
- In turn, the researchers say, the resulting immune system response to chemicals released by the lysing of killed cells could be responsible for the organ damage and failures seen in severe cases of C19.
- Most notably, Brodsky says, the research team found by blocking another complement protein, known as factor D, which works immediately upstream in the pathway from factor H, they were able to stop the destructive chain of events triggered by SARS-CoV-2.
- “When we added a small molecule that inhibits the function of factor D, the APC wasn’t activated by the virus spike proteins,” Brodsky says. “We believe that when the SARS-CoV-2 spike proteins bind to heparan sulfate, it triggers an increase in the complement-mediated killing of normal cells because factor H, a key regulator of the APC, can’t do its job.”
- To better understand what happens, Brodsky says think of the APC like a car in motion.
- “If the brakes are disabled, the gas pedal can be floored without restraint, very likely leading to a crash and destruction,” he explains. “The viral spike proteins disable the biological brakes, factor H, enabling the gas pedal, factor D, to accelerate the immune system and cause cell, tissue and organ devastation. Inhibit factor D, and the brakes can be reapplied and the immune system reset.”
- Brodsky adds that cell death and organ damage from a misdirected APC associated with factor H suppression is already known to occur in several complement-related human diseases, including age-related macular degeneration, a leading cause of vision loss for people age 50 and older; and atypical hemolytic uremic syndrome (aHUS), a rare disease that causes clots to block blood flow to the kidneys.
- Brodsky and his colleagues hope that their work will encourage more study into the potential use against C19 of complement-inhibiting drugs already in the pipeline for other diseases.
- “There are a number of these drugs that will be FDA-approved and in clinical practice within the next two years,” Brodsky says. “Perhaps one or more of these could be teamed with vaccines to help control the spread of C19 and avoid future viral pandemics.”
3. Decoy Cells Trick C19, Reduce Cytokines In Vitro
- Scientists have summoned every trick in the book to develop a C19 treatment over the last few months, from stem cells and synthetic antibodies to common over-the-counter medications and tried-and-true steroids. Some have even attempted to lure the coronavirus (SARS-CoV-2) away from human cells by using molecular decoys. But few have tried to distract the novel coronavirus with fake human cells. Scientists reported in PNAS last week (October 6) that genetically engineered cells can bind and neutralize the coronavirus in vitro. They envision that such cellular decoys could be deployed to combat infections.
- “It’s a very elegant study,” says Karolinska Institute molecular toxicologist Bengt Fadeel, who was not involved in this study. “Provided that you know the receptor of a given virus, you could, in principle, adopt this approach to intercept any virus.”
- Xiaoyuan Chen, a senior investigator at the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health (NIH), pivoted from developing nanotechnology to diagnose and treat cancers to study SARS-CoV-2 when the virus began spreading around the world early this year. He had seen previous reports of using decoy receptors to trick pathogens such as HIV and was curious if the emerging technique might work against SARS-CoV-2.
- To find out, Chen and his collaborators at Wuhan University fused membranes from human monocytic THP-1 cells, a cell line derived from leukemia, with membranes from human embryonic kidney cells that overproduce the ACE2 receptors that SARS-CoV-2 grabs hold of to infiltrate cells. Chen says they hoped that, if the hybrid vesicles were injected in vivo, the virus would ignore unmodified human cells and instead home in on the decoys. Once attached to the engineered cells’ ACE2, the virus would be absorbed and neutralized, according to Chen.
- By embedding monocytic membranes, which have cytokine receptors, into the engineered vesicles, the decoys can bind with inflammatory cytokines such as IL-6, preventing them from building up and causing cytokine storms, overreactive immune responses thought to contribute to more severe C19.
- The idea of a decoy to thwart SARS-CoV-2 infection is not a new one. One team of scientists created a decoy using engineered, free-floating ACE2 receptors that bind especially well with the virus. Their decoys, which the developers propose can “significantly block early stages of SARS-CoV-2 infections,” are now in a Phase 2 clinical trial run by Apeiron Biologics. In a July preprint, pharmacologist Gaurav Sahay of Oregon State University described a method that delivers engineered mRNA that codes for ACE2 to the liver of mice using lipid nanoparticles, causing ACE2 decoys to be translated and secreted into the blood. He found that the method successfully led to an increase of ACE2 decoys in vivo and they inhibited a modified, nonpathogenic version of SARS-CoV-2 in vitro.
- Chen’s new spin on the concept is to couple the decoys with cytokine receptors. “The combination of [ACE2 and cytokine receptors in] the vesicle structure is something new,” says Sahay, who was not involved in Chen’s study. “It’s a very exciting development.”
- Researchers tested the nanodecoys by incubating both SARS-CoV, responsible for the 2003 SARS outbreak, and SARS-CoV-2, which causes C19, in human and monkey cells, and found that the decoys significantly inhibited viral infection, regardless of cell or virus type.
- To test whether the decoys could work outside a petri dish, researchers induced acute lung inflammation in mice by having them inhale lipopolysaccharide, an irritant. Four hours later, the mice inhaled the nanodecoys, and after eight hours, the researchers collected fluid from the mice’s lungs. They found that the decoys successfully mopped up cytokines compared to mice that did not receive decoys.
- “This study is rather straightforward,” says Chen. “It’s surprising that such a simple approach is able to neutralize the virus, at least at the cellular level, and in vivo neutralize cytokines within hours. For C19, a rapid response is essential, and these nanodecoys do just that.”
- While these results suggest that these decoys can neutralize cytokines in mice’s lungs, their ability to block a SARS-CoV-2 infection was not tested in mice. Chen cited a shortage of the transgenic mice bearing human ACE2 that would be needed to conduct such experiments.
- Mice that received the nanodecoys showed no adverse reaction to the treatment, which is encouraging, says Fadeel, but he says he wonders if that would hold true in humans as well, particularly because the engineered cells use material from human cancer cells. “I would be cautious about administering small bits of cancer cells, especially into the lungs,” he says.
- Sahay also notes that cell membranes in the lungs, arteries, heart, kidney, and intestines produce ACE2 for a reason—it cleaves angiotensin, a protein that raises blood pressure. He questions if the decoys might impair the body’s ability to regulate blood pressure, as angiotensin may bind to the decoys.
- Neither Chen nor his colleagues at Wuhan University currently have plans to test the decoys in humans, but he filed a patent for their design through the NIH. “It’s a very simple approach—almost too simple,” says Chen. “That’s the beauty of this study.”
4. Third of newborns with C19 infected before or during birth
- Nearly a third of coronavirus infections in newborn babies are picked up in the womb or from the mother during labour, a review of reported cases has found.
- While C19 is rare in newborns, doctors have been keen to understand the potential risks that babies face should tests reveal they have the infection soon after birth.
- Doctors in France examined 176 published cases of neonatal coronavirus infections in which the infants tested positive at least once or were found to have antibodies against the virus.
- Most of the babies, about 70%, were infected in hospitals where the mother, medical staff, other patients, family members and visitors all posed a potential infection risk. The rest of the infections were passed on directly from the mother before or during birth.
- Daniele De Luca, medical director of paediatrics and neonatal critical care at the Antoine Béclère hospital in Paris, said that despite being rare, it was important for doctors to be aware that newborns can be born with the virus or contract it while in hospital. “At the beginning of the pandemic, some argued that this would never touch babies. It’s rare, but it does exist,” he said.
- The review, published in Nature Communications, found that half of the newborns with coronavirus were asymptomatic. Of those that went on to develop symptoms, 64% had abnormal lung scans, 52% had breathing problems, 44% had a fever, and 36% had difficulties with feeding, diarrhoea and vomiting.
- A small number of the babies, about 18% who fell ill with the virus, developed neurological symptoms ranging from irritability and lethargy to problems with muscle tone that made the limbs either floppy or too stiff.
- The cases in the review may be at the worse end of the spectrum for newborns with C19, since doctors are more likely to report worrying cases and journals are more likely to publish them. De Luca said that even among those reviewed, very few had severe disease and nearly all recovered. Three children included in the review died of unrelated causes.
- After examining how the newborns became infected and what symptoms they developed, the doctors looked at whether mothers with C19 passed the infection on through close contact or breastfeeding. The doctors found no extra risk from breastfeeding, but if the mother was infectious, the chances of passing the virus on to her baby in the first few days were nearly five times higher than if mother and baby were kept apart.
- “We know that keeping the mother and baby together has a lot of advantages, but if the mother is symptomatic, it would be better for some days to be cautious,” De Luca said, adding that the mother may want to express milk so it can be given by a family member until she is no longer infectious. “If they cannot be separated, and in some cases it is impossible, the mother should try to be extra-careful while she is symptomatic, and if possible use PPE and hand gel to reduce the risk of transmission.”
- Dr Helen Mactier, President of the British Association of Perinatal Medicine said: “This paper provides reassuring evidence to add to what we know already. Neonatal C19 is very rare, and generally a mild illness. There is no reason to amend current advice that mother and baby can stay together unless there is a medical reason for the baby to be admitted to a neonatal unit. Really importantly, this paper provides good evidence of the safety of breastfeeding, which should of course be encouraged.”
5. Risk of C19 exposure on planes ‘virtually nonexistent’ when masked
- United Airlines says the risk of C19 exposure onboard its aircraft is “virtually non-existent” after a new study finds that when masks are worn there is only a 0.003% chance particles from a passenger can enter the passenger’s breathing space who is sitting beside them.
- The study, conducted by the Department of Defense in partnership with United Airlines, was published Thursday. They ran 300 tests in a little over six months with a mannequin on a United plane.
- The U.S. Department of Defense published a study Wednesday on cabin airflow that found when a passenger is seated and wearing a mask, only 0.001% of infected air particles could enter their breathing zone.
- The mannequin was equipped with an aerosol generator that allowed technicians to reproduce breathing and coughing. Each test released 180 million particles – equivalent to the number of particles that would be produced by thousands of coughs. They studied the way the mannequin’s particles moved inside the cabin with a mask on and off.
- The tests assumed the flight was completely full with technicians placing sensors in seats, galleys, and the jet bridge to represent other passengers on the plane.
- “99.99% of those particles left the interior of the aircraft within 6 minutes,” United Airlines Chief Communication Officer Josh Earnest told ABC News. “It indicates that being on board an aircraft is the safest indoor public space, because of the unique configuration inside an aircraft that includes aggressive ventilation, lots of airflow.”
- In late September, major U.S. airline CEOs said their employees were reporting lower rates of C19 infection than the general public.
- “At United, but also at our large competitors, our flight attendants have lower COVID infection rates than the general population, which is one of multiple data points that speaks to the safety on board airplanes,” United Airlines CEO Scott Kirby said during a Politico event.
- Last week, the International Air Transport Association (IATA) released new research, saying the risk of contracting the virus on a plane appears to be “in the same category as being struck by lightning.”
- The U.S. Department of Defense published a study Wednesday on cabin airflow that found when a passenger is seated and wearing a mask, only 0.001% of infected air particles could enter their breathing zone.
- Among 1.2 billion travelers, IATA found only 44 published cases of potential inflight transmission. Most of those 44 cases occurred in the early days of the pandemic when masks were not required.
- Air travel is still down around 70 percent compared to last year, but there has been an uptick since the spring. Earlier this week the Transportation Security Administration (TSA) screened nearly a million people at U.S. airports – the agency’s highest number since mid-March.
- “We’re seeing recovery, but we have a long way to go,” Earnest said. “And even with all of this promising information about the safety of air travel and some of the advances that we’re making in terms of implementing a testing regimen – we recognize we’re not going to be anywhere close to back to normal until we have a vaccine that’s been widely distributed and administered.”
6. Remnants of Ancient Parasites Could Be Shaping Our Response to the C19 Coronavirus
- Why are some people more resilient to viruses than others? The answer has eluded scientists for centuries and, in the age of C19, has come to represent one of the holy grails of biomedical research.
- Ed Chuong, an assistant professor of molecular, cellular and developmental biology at CU Boulder, proposes an intriguing answer: Exposure to ancient parasites by our ancestors forever altered our genome, shaping the varied responses of our immune systems today.
- “If you look closely at our genome, viruses have been shaping not only our lives but also our biology and evolution for hundreds of millions of years,” said Chuong, who today was awarded the prestigious $875,000 Packard Fellowship to explore the idea. “It’s possible that ancient viral sequences from past pandemics are now lending a hand in helping us fight modern ones.”
- Say the word ‘genome’ and most people think of the roughly 20,000 genes that encode the proteins necessary for life. But in reality, notes Chuong, we may be more virus than human. Previous research shows that at least half the human genome is made up bits of DNA left behind by viruses and other virus-like parasites, known as transposons, which slipped into cells of our primate ancestors over the past 50 million years.
- “In the human genome we can see traces of these invasions everywhere, like a fossil record of infections,” said Chuong.
- Among those invaders were so-called endogenous retroviruses. As viruses do, they behaved selfishly at first, coaxing their host cells to make more copies so they could rip through the body and infect others. Over time, they lost their ability to sicken and spread, but infiltrated germ cells – like sperm or eggs — baking their genetic recipe into generations to come.
- Scientists long assumed those remnants were useless “junk DNA.”
- But in recent years, Chuong and others have discovered that, in some cases, they were coopted by mammalian hosts for evolutionary gain, influencing everything from cognition to reproduction to immune response.
How viruses made the placenta possible
- In one landmark study, which sparked Chuong’s interest in the field, scientists discovered a protein called Syncytin, derived from an endogenous retrovirus, which made the development of human placental tissue possible. Chuong’s follow-up research, published in the journal Nature Genetics, found that endogenous retroviruses also serve as on-off switches for gene networks that influence placental development.
- “The development of the placenta enabled live birth in mammals and was a major step in the evolution of our species — and these ancient viruses played a key role,” he said.
- Chuong has since shifted his attention to the immune system, showing in 2016 that ancient viruses helped shape the interferon response — the cellular alarm system that sounds within hours of infection.
- “We found fragments of old viruses that normally lay silent but turn on during infection, and when they do, they turn on nearby immune genes,” he said.
- Notably, when those viral fossils are removed and the cell is then infected, the immune response is muted.
- “Our study was one of the first demonstrations of an ancient virus being co-opted for host defense and now necessary to fight modern viruses,” he said.
- Chuong, who arrived at the BioFrontiers Institute in 2018, was working under stay-at-home orders early in the pandemic when he began to think more about why different people respond to infection, including SARS-CoV-2, differently.
- He wondered: Could these ancient retroviruses provide another hidden layer of explanation?
‘A ray of hope for the future’
- Chuong wrote a grant proposal centered around that question. On Thursday, the David and Lucile Packard Foundation named him among 20 early-career scientists across the nation to receive their award.
- “In a year when we are confronted by the devastating impacts of a global pandemic, racial injustice and climate change, these 20 scientists and engineers offer us a ray of hope for the future,” said Frances Arnold, chair of the Packard Fellowships Advisory Panel.
- Chuong suspects that ancient parasites could be influencing human immunity today in one of two ways: Either different populations were exposed to different viruses in their evolutionary history, leaving them with different cellular machinery with which to fight off new threats; or they share the same bits of ancient DNA but much newer influences (in utero or in the environment) have silenced or awakened that immune machinery in ways that make some resilient and others vulnerable.
- To learn more, he and his team will amass population-wide datasets of immune cells from humans and other mammals and apply high-powered computing techniques to sequence their genome, looking not only at genes present but also at transposons.
- “He has pioneered a mind-blowing new way of thinking about how genomics works,” said Lee Niswander, chair of the Department of Molecular, Cellular and Developmental Biology. “For him to be able to follow his nose and see where the science takes him is really exciting.”
- While the science is young, Chuong hopes that it ultimately could lead to new diagnostic tests or even new treatments.
- “Learning how and why immune responses vary within a population could transform our ability to predict individual responses to infection and autoimmune diseases,” Chuong said. “To get this kind of recognition that these ideas are worth pursuing is incredible.”
D. Vaccines & Testing
1. STAT’s C19 Drugs and Vaccines Tracker
- Drug makers around the globe are moving at breakneck speed to advance their Covid-19 vaccine and therapeutic candidates. The race has made one thing clear: The path toward scientific progress will come with bumps in the road.
- Case in point: AstraZeneca has put a large, Phase 3 study of its C19 vaccine — being developed with the University of Oxford — on hold due to a suspected serious adverse reaction in a participant in the United Kingdom.
- Such a hold isn’t uncommon in clinical trials, and it’s not clear yet how long AstraZeneca’s will last. But the status of the company’s trial — and those of the many C19 vaccines and therapeutics currently in development — are being closely watched given the pressing need for new ways to bring the global pandemic under control.
- Linked below are guides to some of the most talked-about efforts to treat or prevent coronavirus infection, with details on the science, history, and timeline for each endeavor (and we will update the tracker with any new developments). The therapies and vaccines are sorted in order of how close they could be to approval, starting with a treatment in Phase 3 trials, followed by others in Phase 1 studies and then preclinical development. Approval, of course, would only come if they are proven safe and effective.
- Treatments here
- Vaccines here
2. Oxford scientists develop 5-minute rapid diagnostic test for C19
- Scientists from Oxford University’s Department of Physics have developed an extremely rapid diagnostic test that detects and identifies viruses in less than five minutes.
- The method, published on the preprint server MedRxiv, is able to differentiate with high accuracy the coronavirus (SARS-CoV-2) from negative clinical samples, as well as from other common respiratory pathogens such as influenza and seasonal human coronaviruses.
- Working directly on throat swabs from C19 patients, without the need for genome extraction, purification or amplification of the viruses, the method starts with the rapid labelling of virus particles in the sample with short fluorescent DNA strands. A microscope is then used to collect images of the sample, with each image containing hundreds of fluorescently-labelled viruses.
- Machine-learning software quickly and automatically identifies the virus present in the sample. This approach exploits the fact that distinct virus types have differences in their fluorescence labeling due to differences in their surface chemistry, size, and shape.
- The test uses a convolutional neural network to classify microscopy images of single intact particles of different viruses
- The scientists have worked with clinical collaborators at the John Radcliffe Hospital in Oxford to validate the assay on COVID-19 patient samples which were confirmed by conventional RT-PCR methods.
- Professor Achilles Kapanidis, at Oxford’s Department of Physics, says: ‘Unlike other technologies that detect a delayed antibody response or that require expensive, tedious and time-consuming sample preparation, our method quickly detects intact virus particles; meaning the assay is simple, extremely rapid, and cost-effective.’
- DPhil student Nicolas Shiaelis, at the University of Oxford, says: ‘Our test is much faster than other existing diagnostic technologies; viral diagnosis in less than 5 minutes can make mass testing a reality, providing a proactive means to control viral outbreaks.’
- Dr Nicole Robb, formerly a Royal Society Fellow at the University of Oxford and now at Warwick Medical School, says: ‘A significant concern for the upcoming winter months is the unpredictable effects of co-circulation of SARS-CoV-2 with other seasonal respiratory viruses; we have shown that our assay can reliably distinguish between different viruses in clinical samples, a development that offers a crucial advantage in the next phase of the pandemic.’
- The researchers aim to develop an integrated device that will eventually be used for testing in sites such as businesses, music venues, airports etc., to establish and safeguard COVID-19-free spaces.
- They are currently working with Oxford University Innovation (OUI) and two external business/finance advisors to set up a spinout, and are seeking investment to accelerate the translation of the test into a fully integrated device to be deployed as a real-time diagnostic platform capable of detecting multiple virus threats.
- They hope to incorporate the company by the end of the year, start product development in early 2021, and have an approved device available within 6 months of that time.
- Read the preprint here: https://www.medrxiv.org/content/10.1101/2020.10.13.20212035v1
3. Remdesivir and interferon fall flat in WHO’s megastudy of C19 treatments
- One of the world’s biggest trials of C19 therapies released its long-awaited interim results yesterday—and they’re a letdown. None of the four treatments in the Solidarity trial, which enrolled more than 11,000 patients in 400 hospitals around the globe, increased survival—not even the much-touted antiviral drug remdesivir. Scientists at the World Health Organization (WHO) released the data as a preprint on medRxiv last night, ahead of its planned publication in The New England Journal of Medicine.
- Yet scientists praised the unprecedented study itself and the fact that it helped bring clarity about four existing, ”repurposed” treatments that each held some promise against C19. “It’s disappointing that none of the four have come out and shown a difference in mortality, but it does show why you need big trials,” says Jeremy Farrar, director of the Wellcome Trust. “We would love to have a drug that works, but it’s better to know if a drug works or not than not to know and continue to use it,” says WHO’s chief scientist, Soumya Swaminathan.
- The prospects of two of the four treatments—the malaria drug hydroxychloroquine and the HIV drug combination ritonavir/lopinavir—had faded after another large study, the United Kingdom’s Recovery trial, showed they did not increase survival in June. After analyzing that study and its own data up until then, WHO decided to drop both from the study.
- There was still hope for remdesivir and for interferon-beta, which had initially been given in combination with ritonavir/lopinavir but was tested as a standalone drug after the Recovery data came out. But neither of those treatments lowered mortality or delayed the moment patients needed ventilation to help them breathe. The results in these two treatment arms are likely to be the most scrutinized.
- Remdesivir, which attacks a specific enzyme in several RNA viruses and was previously tested against Ebola, was initially seen as a promising candidate. In a U.S. trial with more than 1000 C19 patients published last week, those who received remdesivir had a shorter recovery time than patients in the control group, but there was no significant difference in mortality. Two smaller trials found few significant benefits. Remdesivir received an emergency use authorization from the U.S. Food and Drug Administration (FDA) in May for severe C19 patients that was later expanded to include all patients.
- But the Solidarity trial suggests the drug does little in severe cases. Of 2743 hospitalized patients who received the drug, 11% died, versus 11.2% in a control group of roughly the same size. The difference is so small it could have arisen by chance.
- When the authors pooled Solidarity’s data with those from the three other trials, they found a slight reduction in mortality that wasn’t statistically significant either. “This absolutely excludes the suggestion that remdesivir can prevent a substantial fraction of all deaths,” the authors write. “The confidence interval is comfortably compatible with prevention of a small fraction of all deaths but is also comfortably compatible with prevention of no deaths.”
- “This trial doesn’t help remdesivir, that’s for sure,” says Eric Topol, director of the Scripps Research Translational Institute. “It’s not a dead duck as much as hydroxychloroquine, but it certainly is not the hope that was initially signaled.”
- But the drug’s manufacturer, Gilead Sciences, casts doubt on the study. “The trial design prioritized broad access, resulting in significant heterogeneity in trial adoption, implementation, controls and patient populations,” the company says in a statement, “and consequently, it is unclear if any conclusive findings can be drawn from the study results.”
- Gilead received the manuscript about Solidarity on 28 September, according to WHO. On 8 October, before the results became public, the company signed a $1 billion deal with the European Commission for a 6-month supply of the drug.
- Solidarity’s “most disappointing results,” however, are those for interferon-beta, Topol says. Mortality among the 2050 people who received that drug (either alone or in combination with lopinavir/ritonavir) was 11.9%, versus 10.5% in the control group. Prior studies have suggested interferon can only help if given early, however, and not once patients have been hospitalized. “So I think that’s still an open question,” Topol says.
- “Treating COVID late is very difficult,” Benjamin tenOever, a virologist at the Icahn School of Medicine at Mount Sinai, wrote in an email to Science. “At this point in the disease the issue is more about inflammation and clotting, which is likely why these four drug regimens showed little value.”
- The silver lining may be that the trial itself, unprecedented in several ways, succeeded. Set up in a short time in March as the pandemic engulfed the world, it used a simple protocol that allowed doctors in overstretched hospitals anywhere to randomize their patients to whatever study drug was available or to standard care. “To get four different drug strategies nailed down, and in this short period of time and across the world, is just fantastic,” Topol says. “I give them a lot of praise for getting us these results with extraordinary velocity.” “I think that Recovery and the Solidarity trial between them have set the standard of the scale that’s required in order to give you clear answers,” Farrar adds.
- The biggest hurdle was the long time it took to get regulatory approval for the study in some countries, says WHO’s Marie-Pierre Preziosi. “Regulators, as well as the ethics committees for that matter, need to rethink their approaches in pandemics and need to be much more ready to cope with this because sometimes the duration for authorization is really not appropriate.”
- Still, the trial has ramped up to more than 11,000 patients from 30 countries, including Argentina, Peru, India, the Philippines, and Spain, with more slated to join. About 2000 patients are now included every month. For the moment, the remdesivir arm will continue “to get more precise evidence,” says John-Arne Røttingen, CEO of the Research Council of Norway, who heads the executive group of Solidarity’s steering committee. But new drugs will be added, he says.
- As early as next week, Solidarity participants could start to receive acalabrutinib, a cancer drug that inhibits an enzyme that plays an important role in the human immune system. The hope is to soon include targeted therapies such as monoclonal antibodies as well because they are more likely to be successful than repurposed drugs. “Trying to find off-target benefits from FDA-approved drugs is not a great strategy (although arguably the best we can do under these conditions),” tenOever wrote.
- Solidarity built on experience from the 2014–16 Ebola epidemic in West Africa, says Ana Maria Henao Restrepo, who heads the Research and Development Group at WHO. Back then, there were many debates about whether it was even ethical to do randomized clinical trials—which withhold a potential therapy from patients in control groups—during a deadly outbreak. “Now, you don’t see any debate” on that question, she says. “The community, all of us, we have moved, we have learned a lot since West Africa.”
- The study’s global reach has important benefits, says Nahid Bhadelia, a physician at Boston Medical Center. Conducting a trial in many places simultaneously means more patients can be included, leading to faster results but also to more robust data, she says. “You’re including many different types of subgroups and populations in different parts of the world.”
- Another advantage: The 1300 participating doctors worldwide will have a sense of ownership of the results, Henao Restrepo says. “When they see the results in The New England Journal of Medicine, [they will] say, ‘I’ve contributed to that and I understand why that drug works or doesn’t work.
- I know, I trust it,’” she says. “That is different from some Northern Hemisphere group publishing, and they say: ‘Somewhere in a rich country they did a trial and now we all have to believe the results.’”
4. New Blood Test Accurately Predicts Which C19 Patients Will Develop Severe Infection
- Scientists have developed, for the first time, a score that can accurately predict which patients will develop a severe form of C19.
- The study, led by researchers at RCSI University of Medicine and Health Sciences, is published in The Lancet’s translational research journal EBioMedicine.
- The measurement, called the Dublin-Boston score, is designed to enable clinicians to make more informed decisions when identifying patients who may benefit from therapies, such as steroids, and admission to intensive care units.
- Until this study, no C19-specific prognostic scores were available to guide clinical decision-making. The Dublin-Boston score can now accurately predict how severe the infection will be on day seven after measuring the patient’s blood for the first four days.
- The blood test works by measuring the levels of two molecules that send messages to the body’s immune system and control inflammation. One of these molecules, interleukin (IL)-6, is pro-inflammatory, and a different one, called IL-10, is anti-inflammatory. The levels of both are altered in severe C19 patients.
- Based on the changes in the ratio of these two molecules over time, the researchers developed a point system where each 1-point increase was associated with a 5.6 times increased odds for a more severe outcome.
- “The Dublin-Boston score is easily calculated and can be applied to all hospitalized C19 patients,” said RCSI Professor of Medicine Gerry McElvaney, the study’s senior author and a consultant in Beaumont Hospital.
- “More informed prognosis could help determine when to escalate or de-escalate care, a key component of the efficient allocation of resources during the current pandemic. The score may also have a role in evaluating whether new therapies designed to decrease inflammation in C19 actually provide benefit.”
- The Dublin-Boston score uses the ratio of IL-6 to IL-10 because it significantly outperformed measuring the change in IL-6 alone.
- Despite high levels in blood, using only IL-6 measurements as a C19 prognostic tool is hindered by several factors. IL-6 levels within the same patient vary over the course of any given day, and the magnitude of the IL-6 response to infection varies between different patients.
E. Improved & Potential Treatments
1. Research identifies existing metallodrugs as effective treatment for C19
- A research team at the University of Hong Kong (HKU) has discovered a novel antiviral strategy for treatment of C19.
- They discovered that a class of metallodrugs currently used in the treatment of other infectious diseases is showing efficacy to potently suppress the coronavirus (SARS-CoV-2) replication and relieve viral-associated symptoms in an animal model.
- The findings provide a new and readily available therapeutic option with high clinical potential for infection with SARS-CoV-2. This ground-breaking work has been published online in a top-class scientific journal Nature Microbiology. A related patent has been filed in the US.
- Generally, metal compounds are used as anti-microbial agents; their antiviral activities have rarely been explored. After screening a series of metallodrugs and related compounds, the research team identified ranitidine bismuth citrate (RBC), a commonly used anti-ulcer drug which contains the metal Bismuth for treatment of Helicobacter pylori-associated infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo.
- RBC targets the vital non-structural protein 13 (Nsp13), a viral helicase essential for SARS-CoV-2 to replicate, by displacing the crucial zinc(II) ions in the zinc-binding with Bismuth-ions, to potently suppress the activity of the helicase.
- RBC has been demonstrated to greatly reduce viral loads by over 1,000-folds in SARS-CoV-2-infected cells. In particular, in a golden Syrian hamster model, RBC suppresses SARS-CoV-2 replications to reduce viral loads by ~100 folds in both the upper and lower respiratory tracts, and mitigates virus-associated pneumonia. RBC remarkably diminishes the level of prognostic markers and other major pro-inflammatory cytokines and chemokines in severe C19 cases of infected hamsters, compared to the Remdesivir-treated group and control group.
- RBC exhibits a low cytotoxicity with a high selectivity index at 975 (the larger the number the safer the drug), as compared to Remdesivir which has a low selectivity index at 129. The finding indicates a wide window between the drug’s cytotoxicity and antiviral activity, which allows a great flexibility in adjusting its dosages for treatment.
- The team investigated the mechanisms of RBC on SARS-CoV-2 and revealed for the first time the vital Nsp13 helicase as a druggable target by RBC. It irreversibly kicks out the crucial zinc(II) ions in the zinc-binding domain to change it to bismuth-bound via a distinct metal displacement route. RBC and its Bi(III) compounds dysfuntionalized the Nsp13 helicase and potently inhibited both the ATPase (IC50=0.69 μM) and DNA-unwinding (IC50=0.70 μM) activities of this enzyme.
- The research findings highlight viral helicases as a druggable target, and the high clinical potential of bismuth(III) drugs and other metallodrugs for treatment of SARS-CoV-2 infections. Hopefully, following this important breakthrough, more antiviral agents from readily available clinically approved drugs could be identified for potential treatment of C19 infections. They can be in the form of combination regimens (cocktails) with drugs that exhibit anti-SARS-CoV-2 activities including RBC, dexamethasone and interferon-β1b.
2. Drug repurposing study identifies 3 existing drugs that could treat C19
- University of New Mexico researchers who combed through a “library” of previously approved drugs believe they have identified a medication with the potential to help speed a patient’s recovery from the coronavirus (SARS-CoV-2) infection.
- “The gist of it is we think we found a drug that is on par with remdesivir and is much cheaper,” said Tudor Oprea, MD, PhD, professor of Medicine and Pharmaceutical Sciences and chief of the UNM Division of Translational Informatics. Remdesivir is a relatively new antiviral medication that has been shown to shorten hospital stays for those recovering from the novel coronavirus.
- In a paper published this week in ACS Pharmacology & Translational Science, Oprea and his colleagues, in partnership with a team at the University of Tennessee Health Science Center led by professor Colleen Jonsson, PhD, reported that an older antimalarial drug called amodiaquine was effective in eradicating the virus in test tube experiments.
- Tudor Oprea, MD, PhDIt was one of three promising candidates identified in a process that entailed studying the molecular characteristics of about 4,000 drugs approved for human use by the Food and Drug Administration and other agencies. The researchers hoped to find drugs that would target known vulnerabilities in the virus.
- The other two drugs – an anti-psychotic called zuclophentixol and a blood pressure medication called nebivolol also cleared the virus in the experiments, said Oprea, who served as the corresponding author on the new paper. The researchers think any of these three drugs could be combined with remdesivir or a related antiviral drug called favipiravir to mount a more potent attack on the virus.
- Combining two drugs could mean that lower doses of each could be administered, lessening the likelihood of adverse reactions, he said.s Administering two drugs also makes it less likely that the virus would develop a mutation rendering it immune from the treatment.
- “Think of it as a whack-a-mole game,” Oprea said. “Instead of having one hammer, you have two hammers, which is more effective. We’re trying to give the scientific community two hammers instead of one.”
- Many compounds that show antiviral activity in a laboratory setting don’t have the same effect in living organisms, Oprea notes, so the next step is to mount clinical trials to see whether the medications work in COVID-positive patients.
- The UNM drug screening process started with Oprea and his colleague Larry Sklar, PhD, Distinguished Professor in the Department of Pathology. They used computational methods to identify candidate drugs by gauging their similarity to hydroxychloroquine, a since-discredited antimalarial medication that had been widely touted as a C19 treatment. Because of molecular variations in some of the drugs, more than 6,000 combinations were assessed.
- Likely candidates were forwarded to Steven Bradfute, PhD, assistant professor in the Center for Global Health, who tested the compounds against samples of the virus in his Biosafety Level-3 laboratory. Later, the experiments were repeated by the University of Tennessee scientists to provide independent confirmation of the findings – and they used an additional test that reveals the drugs’ potency against the virus, Oprea said.
- Amodiaquine, first made in 1948, is on the World Health Organization’s List of Essential Medicines. It has a good safety profile and is widely used in Africa to treat malaria. Zuclophentixol has been used to treat schizophrenia since the 1970s, while nebivolol has been used for hypertension since the late 1990s.
3. Next C19 Drug Target: Viral “Molecular Scissor”
- American and Polish scientists, reporting in the journal Science Advances, laid out a novel rationale for C19 drug design — blocking a molecular “scissor” that the virus uses for virus production and to disable human proteins crucial to the immune response.
- The researchers are from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and the Wroclaw University of Science and Technology. Information gleaned by the American team helped Polish chemists to develop two molecules that inhibit the cutter, an enzyme called SARS-CoV-2-PLpro.
- SARS-CoV-2-PLpro promotes infection by sensing and processing both viral and human proteins, said senior author Shaun K. Olsen, PhD, associate professor of biochemistry and structural biology in the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio.
- “This enzyme executes a double-whammy,” Dr. Olsen said. “It stimulates the release of proteins that are essential for the virus to replicate, and it also inhibits molecules called cytokines and chemokines that signal the immune system to attack the infection,” Dr. Olsen said.
- SARS-CoV-2-PLpro cuts human proteins ubiquitin and ISG15, which help maintain protein integrity. “The enzyme acts like a molecular scissor,” Dr. Olsen said. “It cleaves ubiquitin and ISG15 away from other proteins, which reverses their normal effects.”
- Dr. Olsen’s team, which recently moved to the Long School of Medicine at UT Health San Antonio from the Medical University of South Carolina, solved the three-dimensional structures of SARS-CoV-2-PLpro and the two inhibitor molecules, which are called VIR250 and VIR251. X-ray crystallography was performed at the Argonne National Laboratory near Chicago.
- “Our collaborator, Dr. Marcin Drag, and his team developed the inhibitors, which are very efficient at blocking the activity of SARS-CoV-2-PLpro, yet do not recognize other similar enzymes in human cells,” Dr. Olsen said. “This is a critical point: The inhibitor is specific for this one viral enzyme and doesn’t cross-react with human enzymes with a similar function.”
- Specificity will be a key determinant of therapeutic value down the road, he said.
- The American team also compared SARS-CoV-2-PLpro against similar enzymes from coronaviruses of recent decades, SARS-CoV-1 and MERS. They learned that SARS-CoV-2-PLpro processes ubiquitin and ISG15 much differently than its SARS-1 counterpart.
- “One of the key questions is whether that accounts for some of the differences we see in how those viruses affect humans, if at all,” Dr. Olsen said.
- By understanding similarities and differences of these enzymes in various coronaviruses, it may be possible to develop inhibitors that are effective against multiple viruses, and these inhibitors potentially could be modified when other coronavirus variants emerge in the future, he said.
F. Concerns & Unknowns
1. Public health experts fear devastating impact of flu and C19 on vulnerable adults
- The National Foundation for Infectious Diseases (NFID) issued a new Call to Action report detailing the risks of co-infection with influenza (flu) and C19 in adults with chronic health conditions, and the importance of flu vaccination during the 2020-2021 season. The goals of the report, The Dangers of Influenza and C19 in Adults with Chronic Health Conditions, have been supported by more than 35 leading medical organizations, including the American College of Cardiology, American College of Emergency Physicians, American Diabetes Association, and American Lung Association, who are now urging their stakeholders to prioritize flu vaccination for these high-risk populations.
- In the US, six in ten adults have one or more chronic health conditions, including heart disease, lung disease, and diabetes, that put them at increased risk for flu and C19. For this population, related complications include the potential exacerbation of underlying health condition(s), as a result of flu-related inflammation that may persist long after the acute infection, as well as increased risk of long-term complications, such as heart attack and stroke, after experiencing acute flu or C19 infection.
- According to the CDC, annual flu vaccination has been proven to mitigate serious flu-related complications, preventing an estimated 7.5 million flu illnesses, 3.7 million flu-associated medical visits, 105,000 flu hospitalizations, and 6,300 flu deaths in 2019-2020 alone. Yet, a recent NFID survey found that nearly one in four US adults at high risk for flu-related complications said they did not intend to get vaccinated during the 2019-2020 flu season.
- “Amidst the C19 pandemic, patients with chronic health conditions are facing not one, but two viruses that pose a serious threat to their health and independence,” said NFID Medical Director William Schaffner, MD. “While we currently don’t have an approved C19 vaccine in the US, we know that annual flu vaccination can help protect these patients from hospitalization, progressive disability, and even death. It is imperative that healthcare professionals educate patients with chronic health conditions about their risks and implement strategies to increase flu vaccination rates during the C19 pandemic.”
- In advance of an unprecedented 2020-2021 flu season, NFID convened a multidisciplinary virtual roundtable with leading experts to explore the risks of co-circulation and co-infection with flu and the coronavirus (SARS-CoV-2) in adults with chronic health conditions. The resulting NFID Call to Action, which summarizes the roundtable discussions, includes best practices for administering flu vaccines in conjunction with C19 mitigation efforts. Despite the limited data currently available on outcomes from co-infection with the two viruses, insights from the roundtable highlighted that the impact on patients and the US public health system could be catastrophic.
- “It won’t take a ‘bad’ flu season–just ‘a’ flu season to make things more difficult in the ER and elsewhere in the US healthcare system,” said Nicholas F. Vasquez, MD, vice chair of the Diversity, Inclusion, and Health Equity Section of the American College of Emergency Physicians. “Further strain due to the co-circulation of flu and C19 could disrupt routine care and have detrimental consequences for adults with chronic health conditions.”
- The relationship between flu and heart disease is of particular concern during the current pandemic, as severe C19 outcomes have also been associated with pre-existing cardiovascular conditions and post-infection injury to heart tissue. Over the past eight US flu seasons, nearly 47% of patients hospitalized for flu had heart disease, making it the most common underlying health condition associated with flu-related complications. Fortunately, flu vaccination can serve as an effective prevention strategy in these patients.
- One study estimated the flu vaccine is between 15 to 45% effective in preventing heart attacks and strokes, making it equal to or more effective than smoking cessation, statins, and antihypertensive therapy.
- “I am greatly concerned for heart disease patients this flu season. It is already well-documented that heart disease is a risk factor for severe flu-related illness, but with C19, we are entering a dangerous and uncharted territory,” said William B. Borden, MD, professor of medicine and health policy at George Washington University, representing the American College of Cardiology. “The most important thing we can do to protect these patients is to ensure they are getting their annual flu vaccine. I am making it a point this season to strongly recommend a flu vaccine to every heart patient I see and urge my colleagues to do the same.”
- To help increase flu vaccination rates, the NFID Call to Action offers strategies and tactics for healthcare professionals, particularly specialists treating adults with chronic conditions during the 2020-2021 flu season, including communication methods for discussions with both patients and office staff, vaccine implementation strategies specific to the C19 pandemic, and techniques for addressing vaccine misinformation.
- “All healthcare professionals, including specialty care providers, have a duty to understand the risks our patients face and advocate for any preventive measure that can preserve health and save lives,” said NFID President Patricia N. Whitley-Williams, MD, also representing the National Medical Association. “If you treat a patient with heart disease, lung disease, diabetes, or another chronic health condition, then you have a responsibility to insist upon annual flu vaccination.”
2. Study reveals kidney disease or injury is associated with much higher risk of mortality for C19 patients in ICU
- New research published in Anaesthesia (a journal of the Association of Anaesthetists) reveals the much higher risk of mortality faced by C19 patients in intensive care who have chronic kidney disease (CKD) or, those who develop new (acute) kidney injury (AKI) as a result of developing C19.
- CKD is a type of kidney disease in which kidney function declines over a period of months to years, and is more common in older people. There are five stages of the disease, ranging from early stages (1 and 2) in which people initially have no symptoms, through to the more serious stages 3 to 5, which can be associated with complications such as high blood pressure, type 2 diabetes and heart disease. CKD stage 5 is termed end stage kidney failure which must be treated with either dialysis (at home or in hospital), involving complex filtering machinery that takes over the blood-cleaning functions of the kidneys, or with a kidney transplant.
- AKI is an abrupt loss of kidney function that takes place over seven days or less, and can have several causes, including the damage and inflammation caused by the C19 virus itself, loss of blood flow to the kidneys, damage from pharmaceutical drugs or other ingested/injected substances, or by anything obstructing the flow of urine in the urinary tract.
- This new study, led by Dr Sanooj Soni from Imperial College London, UK, and colleagues, examined the association between AKI and CKD with clinical outcomes in 372 patients with C19 admitted to four regional intensive care units (ICUs) in the UK between 10 March 23 July 2020 (Hammersmith Hospital, London; St Mary’s Hospital, London; Charing Cross Hospital, London; and Queen Elizabeth Hospital, Birmingham). The average age of the patients was around 60 years, and 72% of them were male. Also of note was the fact that the majority of patients were of Black, Asian of Ethnic Minority (BAME) background (281 patients, 76%).
- A total of 216 (58%) patients had some form of kidney impairment (45% developed AKI during their ICU stay, while 13% had pre-existing CKD), while 42% had no CKD or AKI. The patients who developed AKI had no history of serious kidney disease before their ICU admission (known from blood tests either at admission to hospital or from their medical records), suggesting that the AKI was directly related to their C19 infection.
- The authors found that patients with no kidney injury or disease had a mortality of 21% (32/156 patients). Those with new onset AKI caused by the C19 virus had a mortality of 48% (81/168), whilst for those with pre-existing CKD (Stages 1-4) mortality was 50% (11 /22). In those patients with end-stage kidney failure (i.e. CKD stage 5), where they already required regular out-patient dialysis, mortality was 47% (9 of 19 patients). Mortality was greatest in those patients with kidney transplants, with 6 out of 7 patients (86%) dying, highlighting that these patients are an extremely vulnerable group.
- The investigators also examined the rates of renal replacement therapy, a form of hospital dialysis, due to C19 in these ICU patients with kidney injury. Out of 216 patients with any form of kidney impairment, 121 (56%) patients required renal replacement therapy (see Table 2 full paper). Of the 48 survivors who needed dialysis for the first time during their ICU stay, 9 patients (19%) had to continue with dialysis after discharge from ICU, suggesting C19 may lead to chronic kidney problems.
- “To the best of our knowledge, this is the first comprehensive analysis of outcomes in critically unwell C19 patients in the UK with kidney failure, particularly in patients with pre-existing chronic kidney disease,” say the authors.
- The authors note their surprise that mortality in patients with end-stage kidney failure and on dialysis, who normally have worse outcomes in many other diseases, was similar to that in patients with less severe kidney disease and C19 associated AKI. This finding may suggest that such patients benefit equally from ICU admission and thus the threshold for admission should be calibrated accordingly in any future C19 surge. Put another way, these results suggest that patients on dialysis with C19 appear as likely to survive as patients with less serious CKD or AKI and can be considered for admission to an ICU bed.
- However, the authors recommend caution interpreting these results due to selection bias – meaning that in this study only patients who were cared for in ICU during the peak of the last surge were included and other patients with end stage kidney failure, who may have been too unwell for admission to ICU, were not. This may have contributed to these findings of similar mortality in patients with end-stage kidney failure compared to those with less serious forms of CKD and AKI.
- The reasons for the increased mortality in patients with kidney problems are not clearly understood. There are several theories, including that the C19 virus causes endotheliitis, an inflammation of the blood vessels in the kidneys, which is similar to the problem C19 is known to cause in the lungs. Other reports have suggested that there could be direct kidney injury from the cytokine-induced immune system inflammatory response (where the body is overwhelmed by its own immune response, the so-called cytokine storm), and also death of kidney tissue related to multi-organ failure caused by C19.
- The authors conclude: “Our data demonstrate that kidney disease and failure in critically ill patients with C19 are common, and associated with high mortality. However, important differences exist between stages of acute and chronic kidney disease in how they affect mortality in patients with C19 and patients who have had a kidney transplant are an extremely vulnerable group. In view of this, attention needs to be paid to C19 patients with any form of kidney disease or injury, and every effort made to prevent progression of this disease or injury to reduce mortality in this cohort of patients.”
3. New coronavirus strain found in swine could jump to humans
- An emerging coronavirus strain that causes gastrointestinal illness in swine – and is especially dangerous to baby pigs – could wreck the pork industry and has the potential to jump species and infect humans, a University of North Carolina study has found.
- The study, published this week in the Proceedings of the National Academy of Sciences, looked at a virus called swine acute diarrhoea syndrome, or Sads-CoV, that began to infect swine herds in China in 2016, causing diarrhoea and vomiting.
- It killed 90% of the piglets under five days old that contracted it.
- The virus, which has not been detected in the United States, is in the same family as the coronavirus (Sars-CoV-2). Both viruses are thought to have emerged from bats.
- Caitlin Edwards and Rachel Graham of UNC’s Department of Epidemiology said on Thursday in a phone interview with The News & Observer that the team submitted its findings for publication in early 2020, before the C19 pandemic hit.
- But the swift spread of C19 around the globe this year has emphasised the need for developing interventions for coronaviruses.
- “If this virus did occur in the US, the primary concern would be the swine industry,” Graham said. But in experiments, the virus was able to adapt and use human liver, gut and airway cells as hosts. “We know it infects human cells,” Graham added.
- The most likely way for the virus to move to humans would be through contact such as between workers and animals at hog farms.
- China is the world’s larger swine producer, followed by the European Union and the United States. In the US, the industry is concentrated in the Midwest and in Eastern North Carolina.
- In reporting its findings, the team recommended continued surveillance in China, for the spread of Sads-CoV in swine herds but also for the appearance of unexplained illnesses in people.
- China is monitoring the virus among animals, Edwards said, because of the cost of the ongoing outbreak. But knowing that it could jump species means China also needs to monitor for “spill over” into humans.
- In terms of human illness, Edwards said, the Chinese need to be looking for “anything that we haven’t seen before”.
- Graham added: “The tricky part is we don’t know what kinds of diseases would manifest” if the virus crossed over to humans.
- While the virus causes gastrointestinal issues in swine, it might produce respiratory or other issues in people, she said.
G. The Road Back?
1. Fractal Signatures of C19 Transmission Could Reduce Socio-Economic Impact of Lockdowns
- The most widely used model to describe the epidemic evolution of a disease over time is called SIR, short for susceptible (S), infected (I), and removed (R). A susceptible person can be infected, and the infected person will eventually be removed owing to either immunization or death. The number of people in each class varies, whereas the total population, given by the sum of individuals in all three classes, is considered constant in the time scale of epidemic contamination.
- The function I(t) resulting from the model describes the increase in the number of infected people over time. The curve rises sharply during the phase in which the pathogen is spreading quickly, peaking at maximum contamination, and sloping down more gently as contagion slowly decreases until there are no longer any infectious people. The SIR model has been applied in several studies of the C19 pandemic.
According to this assumption, agents of different scales carry the virus to other agents of the same scale in a similar fashion, as depicted in the figure. The model developed on the fractal assumption is used to explain details of the time series spread of the disease.”
- “Although this model is a very useful tool to investigate the temporal evolution of the pandemic, it provides few insights into how contagion progresses spatially, which is key to the planning of social distancing programs that effectively protect people and at the same time reduce the socio-economic impact of the disease,” Airton Deppman, a professor in the University of São Paulo’s Physics Institute (IF-USP), told Agência FAPESP.
- Deppman is one of the authors of a paper published in the journal Chaos, Solitons & Fractals reporting some of the findings.
- The study was supported by FAPESP via a Thematic Project for which Arnaldo Gammal is principal investigator and Deppman is one of several co-principal investigators.
Scaling behavior of the number of contamination cases as a function of region population in a) China, b) USA, c) France, Germany, Spain and Italy together and d) São Paulo State in Brazil, by city population. The confidence intervals are drawn at 95% confidence level.
- The results point to the fractal nature of transmission in the case of C19, as is also the case for many other variables relating to social life. This means contagion occurs discontinuously but in accordance with the same pattern at different scales. An infected person initially transmits the virus to a relatively small group with which he or she is in direct contact. Then there is a gap in transmission, followed by another phase in which the initially infected group transmits the virus to a larger group, and so on.
- “When you construct a graph crossing the number of infected people with the population and quantify the variables on a logarithmic scale on the x and y axes, the result is a straight line. This is typical of a fractal phenomenon, in which the same pattern is repeated at various scales,” Deppman explained.
- The study investigated this spatial distribution using data for China, the United States, and the state of São Paulo and tested the results by comparing the data for São Paulo and Europe. “The model successfully described in great detail the temporal evolution of contagion,” Deppman said. “As a rule of thumb, the curve rises steeply at first, and this is followed by smaller peaks and troughs as the virus is transmitted from one area to the next.”
- The model can be used to find an optimal point at which to begin and end isolation, which should happen region by region and not generically for an entire state or country, he concluded.
2. Forget C19. This doctor is worried about C20
- We’re now embroiled in the COVID-20 “syndemic,” says a provocative commentary in Disaster Medicine and Public Health Preparedness.
- Syndemics are clusters of multiple diseases that exacerbate each other and are often fueled by socioeconomic details like poverty and health disparities. James J. James, MD, PhD, MHA, the former director of the American Medical Association’s Center for Public Health Preparedness and Disaster Response, argues that while the epidemic began as a singular virus with public health officials aiming to contain and mitigate it, this is no longer the case:
- Collateral damage from social isolation and school and business closures is enormous, resulting in a domino effect of problems such as mental health struggles and stopped treatments.
- Some populations, such as elderly, Black, and poor communities, are much more vulnerable to severe and lethal outcomes, and those communities require interventions far beyond what the medical community can provide.
- COVID-20 is a large-scale crisis that is deeply enmeshed in social and environmental factors. Simply containing and mitigating the virus is no longer an option, nor is it likely that a potent vaccine will be provided to much of the world’s population.
- James notes that infection is now so widespread that perhaps we should consider the virus to be chronic and endemic, much like HIV/AIDS, and approached as such.
- James hopes that a name change to COVID-20 will damper the sharp fear born of the early days of COVID-19 into a more rational discussion of ongoing risks, behaviors, and responses, as well as nudge media to stop reporting COVID-19 cases as raw numbers, which he says does not adequately convey the context.
H. Back to School!?
1. Schools (and Children) Need a Fresh Air Fix
- One day in March, the kids were there. The next day, there was no one. Then on a Saturday in August, a man came into an empty public school in suburban Boston carrying a container of dry ice, trying to figure out how to bring the students back to their desks.
- Since January, that man, Joseph Allen, a professor at Harvard’s School of Public Health, has been saying to anyone who will listen that air—the stuff that everybody breathes and nobody thinks about—has got to move. Before the lockdown, his lab’s whiteboard was dense with notes about how the SARS-CoV-2 coronavirus might spread indoors. Trapped at home, he wrote scads of op-eds, talked to journalists, and was one of the scientists who reviewed an open letter to the World Health Organization demanding that it acknowledge that the virus can be spread through tiny particulates in the air.
- With the billowing plumes of dry ice, Allen, his team, and the school’s maintenance employees conducted experiments, measuring the flow of air in various buildings. If Allen has anything to say about it, in some classrooms this fall you might see a fan with a crinkly white HEPA filter strapped to it. In the walls, ventilation systems may be fitted with filters too. As long as the weather permits it, windows will be flung open and wedding tents will be pitched on fields, as school administrations focus on what seems like a simultaneously simple and overwhelming task: Move the air around. Filter it. Dilute it.
- While physical distancing and mask wearing help cut down transmission via larger droplets, when it comes to airborne transmission, ventilation and filtration, which reduce the concentration of virus floating in the air, will also be key to making indoor spaces safer.
- Allen, who worked as a safe-buildings consultant before entering academia, has been helping schools, universities, and daycare centers work on plans for reopening. “Very often I get the comment, ‘Oh! You’re the first person we’ve heard talk about ventilation!’” Allen says. “That’s deeply concerning.”
- The pandemic spotlights a problem that Allen and his colleagues have known about for years, but that most other people have no clue about: Schools are chronically under-ventilated. A commonly used standard for air movement says that, at minimum, 15 cubic feet per minute (cfm) per person should flow into a classroom; Allen says that for Covid prevention, he recommends 30 cfm. But studies show many American classrooms have an average ventilation rate of only 6 to 11 cfm per person.
- Even when there isn’t a pandemic going on, that’s not good, because a substantial body of research suggests that better air flow is correlated with increased test scores and reduced absences. At least one study using air filters in classrooms also found increases in student achievement.
- The care and feeding of air fell out of public consciousness a long time ago, though. So as fall approached, Allen and his colleagues released a detailed report on how to open schools more safely and provided guidance to those who’ve reached out to them. “The problem is, we’ve lost our way over the years,” Allen says.
- It’s taken a worldwide pandemic to get us to pay attention to the air children breathe.
- When it came to designing buildings, airflow used to be way up there on the priority list. After much of Britain’s parliament building, the Palace of Westminster, burned in 1834, David Boswell Reid, a doctor, chemist, and inventor, was asked to handle the ventilation of the new building. Members of Parliament had found the old building stuffy, and serious air pollution in London made cracking open a window a risky and extremely unpleasant move. Reid had developed an elaborate ventilation system for his private lab in Edinburgh, and he spent the next few years testing and perfecting his design for Parliament. His plan relied on the natural buoyancy of gases to pull air out of debating chambers and draw fresh air in, and even used wet canvas to filter out pollution. In the temporary House of Commons, he put in an entire ecosystem of ducts that vented air up through flues on the roof. In Reid’s design for the permanent structure, towers that look like Gothic whimsies are, in fact, functional tools for ventilation.
- Keeping the air at a comfortable temperature was Reid’s overriding concern, but he also strove to keep fresh air circulating. For much of the 19th century, the prevailing theory was that diseases like malaria or cholera were caused by miasmas, or “bad air.” The theory was invoked to explain why people living near swamps got sick (today we’d probably say mosquitoes) and why slums were festering pits of disease (we’d now put it down to poor sanitation). And yet they were on to something when it came to air movement.
- Medical professionals of the time noted that sunshine and fresh air seemed to have salutary effects. One of the strongest proponents of ventilation was Florence Nightingale, who trained nurses during the Crimean War. Increasing the flow of air reduced the spread of disease among soldiers, she found. “Keep the air he breathes as pure as the external air,” she famously wrote. In Nightingale’s writings, there’s more than a whiff of miasma theory, but while she may have been wrong about the cause, the solution was apt. It wasn’t until the very end of the 19th century that germ theory—how we currently explain illness—caught on. It’s true that ventilation can reduce disease, but it probably does so by reducing the concentration of pathogens in the air.
- With the understanding that germs cause disease, rather than some mystical quality of the atmosphere, previous eras’ emphasis on ventilation started to look a bit silly. Then, in the 1970s, a worldwide energy crisis put ventilation even further out of favor. In the name of energy efficiency, schools and office buildings were increasingly designed with windows that didn’t open. This lowered heating and cooling bills, but it meant less air was moving in and out. In his 1986 book Home, architect Witold Rybczynski writes somewhat condescendingly: “No nineteenth-century book on houseplanning was complete unless it included at least one chapter on the subject of ventilation and ‘the evils of bad air.’”
- Many of us might think of a stuffy office building or classroom as a temporary inconvenience. But stagnant air may affect us in ways we don’t always realize. Inadequate ventilation is linked to worse performance on cognitive tasks in office workers, Joe Allen’s group has found. At Lawrence Berkeley National Labs, scientists have been studying indoor air quality in schools for decades. Using surveys that ask students if they have any respiratory symptoms and correlating the responses with how much fresh air classrooms get, they’ve found that, after controlling for factors like socioeconomic status, more fresh air is linked to fewer symptoms, says Rengie Chan, a research scientist at LBL. What’s not clear is whether this connection is related to long-term health benefits of breathing fresher air or to lower pathogen concentrations in the air, or some other factor.
- Other research has found an association between ventilation and learning, as well. In one study, the scientists had students take tests in rooms whose ventilation they controlled. They found that students in better ventilated spaces had better scores. “There’s pretty strong evidence that improved ventilation will get you improved student performance,” Chan says. There is also evidence, albeit more mixed, that better ventilation reduces absences.
- The science has yet to penetrate into practice, though. In one study, co authored by Chan, 85 percent of the California classrooms included failed to meet the minimum standard of 15 CFM per person. Across the country, many classrooms have unit ventilators, big metal boxes that sit against exterior walls and push air out and suck fresh air in. (Allen often sees them covered with books or potted plants.) Some schools have centralized systems with vents in the ceiling. But even in schools with upgraded systems, Chan and colleagues at LBL and UC Davis found that about half of classrooms still didn’t get enough fresh air, because controls were not set to adequate ventilation, or the systems weren’t maintained or installed correctly.
- People are starting to realize this is an issue, even on the level of the federal government, Chan says. A Government Accountability Office report from before the pandemic found that 40 percent of schools needed to upgrade their HVAC systems. But, when the novel coronavirus pandemic hit, not much had been done.
- Outside that-Boston area school this summer, Allen and his team found an unobtrusive vent in the white-painted brick wall and wrapped it in blue fabric. In this way, the air coming out of the classroom on the other side of the wall was funneled into a small black box called a balometer. On the device’s screen, a number popped up, revealing just how much air was moving out of the classroom.
- This was the first step in what Allen says is a pretty simple way to reduce the likelihood that SARS-CoV-2 will spread in schools.
- Allen estimates that for reducing Covid-19 risk, the air in the room should be completely replaced at least five times an hour. In that Boston school, the balometer registered about 400 cfm of fresh air coming in through the unit ventilator in one classroom. The room measured 1,010 square feet and had 9.5 foot ceilings: It had 9,595 cubic feet of air. Multiply 400 cubic feet per minute by 60 minutes, divide it by the volume, and you find that the air only gets turned over 2.5 times an hour. That’s subpar by Allen’s standards.
- Opening the windows and doors could boost that number past five, sometimes far higher. Allen and his team confirmed that finding this summer, when they placed dry ice, which produces carbon dioxide, in classrooms to mimic a room full of people. With a cheap carbon dioxide sensor, they could see how quickly the CO2 dissipated. “In one, when the windows and doors were open, we were at 17 to 20 air changes per hour,” Allen says.
- When windows and doors can’t be opened—which will become more of an issue as cold weather arrives—installing a filter in the unit ventilator or the central ventilation system can help. While the air itself isn’t always coming from out of doors, it’s been pushed through a filter. Viruses travel in tiny specks of fluid, and these specks are large enough that they can be captured by filters of a certain grade. MERV13, which pulls out particles as small at 0.3 microns, is the rating that Allen suggests for this situation. When that’s not an option, the next best choice is to add in a portable air cleaner, which, again, is just a HEPA filter and a fan.
- In a spreadsheet tool that Allen’s team and their collaborators at the University of Colorado created, you can calculate how big an air cleaner you need (click here to access the calculator). You put in the room’s volume and a guess at how well ventilated it is already, and you get an estimate for how hefty a cleaner you need to bring it up to at least five room changes per hour, along with examples of products that meet that description. Thomas Talhelm, the founder of SmartAir, a social enterprise that makes simple, inexpensive air cleaners, says that interest has definitely increased this summer.
- But in the long term, beyond this pandemic, a better awareness of ventilation could benefit both students and teachers.
- “I hope beyond hope we have an effective vaccine. But we may not. And we probably won’t this school year, and we may not in the next three years,” says Westyn Branch-Elliman, an infectious disease doctor at Beth Israel Deaconess in Boston and a former hospital epidemiologist who has written about school openings. “We need to come up with a multiyear plan, as opposed to a week- or month-to-month plan.”
- Developing the infrastructure for better ventilation could be a long-term boon, and not just for preventing Covid-19. “There are all these benefits we’ll continue to reap for years to come, in terms of better health outcomes and better academic performance, better attendance,” notes Emily Jones, one of Allen’s graduate students. “It’s a no-lose scenario to invest in ventilation in schools.”
- So far, the Harvard report has been downloaded more than 7,000 times, and the report’s site has logged more than 112,000 visits in a couple of months.
- “This is a time for the basics of healthy buildings,” Allen says. “And that’s bringing more fresh outdoor air in.”
- Those big plumes of CO2, drifting through empty classrooms, almost recall the vapors of miasma theory. But this time, there’s modern science behind it.
2. Day-Care Centers Are Very Low Risk for C19 Transmission
- Children in day-care programs present virtually no risk of transmitting C19 to adults, according to a new Yale University study of more than 57,000 U.S. child-care providers.
- The study, believed to be the largest of its kind, indicated that keeping child-care centers open doesn’t contribute to transmission of the disease caused by the new coronavirus, as long as they hew to sanitary guidelines like hand washing, small group sizes and staff wearing face coverings.
- The research has broad implications for the U.S. economy, parents who depend on day-care centers and child-care workers. More than a third of child-care centers in the country closed between March and July, according to Child Care Aware, an advocacy group.
- A June survey by the National Association for the Education of Young Children found that child-care center enrollment fell by 33% nationwide and that 70% of providers reported that parents told them they weren’t comfortable sending kids back to day care.
- “For parents, it might be a little bit of cold comfort, because they’re worried about their particular child,” said Dr. Walter Gilliam, a child psychologist at Yale and lead author of the study, published Wednesday in the journal Pediatrics. “But it’s clear that child care doesn’t pose a threat to communities.”
- Risk of infection for child-care professionals appears to be comparable with that for the broader population. The Yale study sought to control for factors such as the level of infection in the community where each center was located, as well as the gender, age and ethnicity of providers.
- “It doesn’t appear that working in child care leads to the spread of C19,” Dr. Gilliam said. “It is true that many child-care providers did get sick. Many of them even went to hospitals. But it was not the contact with children in child care that seems to be the source of that infection.”
- The paper adds to growing research showing that young children aren’t major vectors in C19 transmission, said Dr. Kristin Moffitt, a physician at Boston Children’s Hospital and professor of pediatrics at Harvard Medical School.
- Scientists aren’t sure why children under the age of 10 seem less likely to spread the virus, but some theories have included a smaller viral load in their airways, smaller fluid droplets expelled when they cough or sneeze, or simply that small children are closer to the ground and thus less likely to transmit particles to adults’ airways. Most day-care centers go up to ages 5 or 6.
- Outbreaks have been more common among high-school and college students, in part, scientists believe, because they are more independent than young children and interact more with peers.
- “You would think that day cares would be hotbeds, but they’re not, and this study is consistent with that,” Dr. Moffitt said. “The younger the age of the population, the less they seem to be contributing to transmission.”
- The Yale study “provides a very important window into a crucial topic” and was conducted with a solid methodology, said Renee Boynton-Jarrett, a professor of pediatrics at Boston University School of Medicine. Both Drs. Moffitt and Boynton-Jarrett read prepublication copies of the study, though neither was involved with its peer-review process.
- Dr. Boynton-Jarrett cautioned that the Yale study doesn’t indicate that children in day cares are immune to the disease, although most research shows that adults suffer from more intense bouts of C19 than most children. According to the U.S. Centers for Disease Control and Prevention, 296 children under the age of 14 had died from the infection through Oct. 7, or 0.14% of total U.S. deaths.
- Survey responses in the study indicated that most professional child-care centers have rigidly observed guidelines like mask wearing, hand washing and contact tracing, the authors noted. While all day-care programs have low transmission rates, adults involved in home-based child-care programs were slightly more likely to become infected than those working in commercial day cares, the study said.
- The Olive Treehouse Group, a network of three private preschools in Brooklyn, N.Y., with a total capacity for 90 children, closed its doors between March 13th and July 22nd. During that time, parents permanently pulled 25 students from the schools and the group lost 40% of the year’s revenue, its executive director, Ashley Sobel, said.
- Many parents who used to send their kids to the school described anxiousness around the uncertainty caused by various state and local orders to close, reopen and modify service at schools and child-care centers, Ms. Sobel said. Many of these parents pulled their kids from child care as a result.
- Last week, New York Gov. Andrew Cuomo declared child-care centers to be essential services and said they wouldn’t be ordered closed again. The move has prompted a flood of returning parents, Ms. Sobel said, and the Yale report will come as good news to them.
- “Some families wanted to get back to the pre-shutdown normalcy as quickly as possible but a lot of them fear that second wave and anticipate another shutdown,” Ms. Sobel said.
- Some parents, like Tzur Frenkel, an engineer who lives in Pittsburgh, have already adjusted to the new normal and are unlikely to be swayed by new research.
- In March, the day care at a nearby synagogue attended by Mr. Frenkel’s two children, then 5 and 3 years old, closed its doors. The children are still at home, even though most child-care centers in the city have reopened, and the family has struggled to rearrange its schedule around child-care needs.
- Mr. Frenkel’s wife, a pharmaceutical researcher, is pregnant—considered a high risk case for C19 by public health officials—and they worry one of their children could bring the infection home from day care.
- “We didn’t want to take any chances,” said Mr. Frenkel. “We decided it’s not worth the risk, even though there are a lot of benefits to day care.”
3. How a pioneering C19 testing lab helped keep northeast colleges open
- Twice a week, students at Williams College in Williamstown, Mass., go to a parking garage to blow their noses.
- After clearing their nostrils, they douse their hands in sanitizer, then proceed to a tent where, under the watchful eyes of trained emergency medical technicians, they swab their nasal passages. Then they stick the swab into a vial, the vial into a box, sanitize their hands again, and head out.
- Once the testing site closes each day, Rita Coppola-Wallace , Williams’s executive director of planning, design and construction, gathers the bounty—up to 1,100 test tubes—and loads them into a waiting car. The samples are whisked off to Cambridge, Mass., 150 miles away, and processed alongside tens of thousands of others overnight at the Broad Institute of MIT and Harvard, a biomedical and genomics research center.
- A primary reason many colleges in Massachusetts, New York, Maine and Vermont have experienced few coronavirus outbreaks this fall has been frequent, widespread testing. At 108 colleges and universities, that testing is being done within a carefully orchestrated system run by the Broad Institute.
- The testing, along with strict, state-level quarantine orders and low levels of community spread in the region, has helped keep infection rates at schools working with Broad below 0.2%.
- Broad first planned to work with a group of Massachusetts private colleges that approached the lab in the spring. Then it added public universities around the state. Other schools in Maine, New Hampshire, Vermont, New York, Rhode Island and Connecticut caught wind, and Broad soon had 108 partners and a waiting list.
- The nerve center for the operation is tucked inside a large, low-slung concrete building that once served as an Anheuser-Busch beer distribution warehouse where Broad’s Genomics Platform runs an automated, licensed laboratory for genome sequencing.
- Williams College’s C19 testing tent complex is on the third level of a parking garage on campus.
- Williams College students enter and exit the loop of tents set up for C19 testing at Williams College.
- A student places the swab in her personalized vial after self-administering the test at the swabbing station at Williams College.
- The lab had never run a viral diagnostic test before March 23. Under the supervision of Stacey Gabriel , senior director of the Genomics Platform, it now regularly processes more than 70,000 tests a day—about 45,000 of them from colleges and universities—and has the capacity to go up to 100,000. Other tests come from area nursing homes and hospitals.
- Dr. Gabriel said she and other Broad leaders were dismayed by the state of testing back in the early spring and wanted to help respond to the public health crisis. Broad handles between 10% and 20% of all C19 polymerase-chain-reaction tests done in the U.S., Dr. Gabriel said. Last week, it processed its three millionth test, and it has inspired others to pursue large-scale, low-cost testing outside commercial labs.
- “We really borrowed a lot of industrial principles of how factories are organized and how factories plan their work,” she said. “It’s an automated assembly line.”
- One of the biggest logistical hurdles early on was getting an IT system established that would enable Broad and its partner schools to track their supplies and testing results.
- “The testing part is not the hard part,” Dr. Gabriel said. “It’s the surrounding activity of testing—the ordering of the tests, the collection of the sample, the accession, the bringing it into the lab, those are the bottlenecks.”
- Because schools gather their samples during the day, dozens of couriers arrive with vial-filled coolers between 5 p.m. and 10 p.m. “There’s a crush of samples that shows up,” Dr. Gabriel said. “Our night shifts are very busy.”
- Broad received funding from the state and a National Institutes of Health contract to scale up. The lab used to have 125 staff members; it hired another 250 in recent months to handle the load.
- Workers at the Broad Institute scanning barcodes on patient samples. It handles between 10% and 20% of all C19 PCR tests in the U.S.
- The CDC at first urged schools to focus on testing symptomatic individuals and played down the need for entry or surveillance tests. In a late-September update, however, the CDC said those measures combined “might prevent or reduce” C19 transmission.
- It also said schools’ various approaches, from regular surveillance to no screening at all, “is an emerging area, and there is currently limited scientific evidence to guide decisions to use or not use one of these strategies.”
- A. David Paltiel, a professor of public health at the Yale School of Medicine who ran an epidemiological modeling study on the new coronavirus this summer, called that latest conclusion “disingenuous and unscientific.”
- His study, published in the Journal of the American Medical Association, found that testing all students every two days may be the threshold for safe college operations. Just screening for symptoms led to broad-based C19 outbreaks in the model.
- “Testing is like an early-warning missile system,” said Laurie Leshin , president of Worcester Polytechnic Institute. By identifying a positive case quickly, she said, schools can “manage it before it does a lot of damage.”
- College staff and students over the age of 18 swab their noses, place the swab in personalized vials and sanitize their hands at the testing complex.
- As colleges convened in the spring and summer to discuss their options for reopening, testing emerged as a centerpiece of many plans. But commercial labs quoted prices over $100 for each test, meaning frequent checks of large populations would sink many schools’ budgets. And those labs’ projected turnaround time, three to four days, was a nonstarter given the need for immediate isolation in crowded dorms.
- Broad sold tests to school partners for $25 a piece. It initially promised test results in 24 hours; its turnaround time is now averaging around 14 hours.
- That has allowed Bates College in Lewiston, Maine, to test students twice a week; its positivity rates remain around 0.01%.
- More-urban campuses are faring well, too. Tufts University, with campuses in Boston and Medford/Somerville, Mass., has conducted more than 95,000 tests so far on roughly 11,000 students, staff and faculty, and reported a 0.04% positivity rate [38 positive tests].
- Worcester Polytechnic, located in downtown Worcester, Mass., has committed to a total 125,000 tests with Broad for the fall term. It recorded six positives in the past month, or 0.018% of all tests.
- “For those of us that don’t have massive biomedical research complexes, for those of us that are smaller colleges, it’s been a lifeline to be able to reopen,” Dr. Leshin said of the Broad partnership.
- Some other schools have created their own high-volume labs. Dr. Gabriel commended the saliva-based testing program of the University of Illinois, Urbana-Champaign, as well as the testing apparatus at the University of Washington and Boston University.
- Williams was in talks to join with the local health system in late spring and early summer to handle campus testing. But a 72-hour turnaround time “was just a no-go,” said Fred Puddester , vice president for finance and administration and treasurer.
- Rita Coppola-Wallace, Williams College’s executive director of planning, design and construction, taped up boxes of the day’s tests with Tim Reisler of the facilities staff on Oct. 8.
- Mr. Puddester said he expects Williams to spend between $2.5 million and $3 million for tests from Broad, and up to $1 million more for related costs such as the tent rental, ID card readers, signage, paying EMT and other staff “and gallons and gallons of hand sanitizer.”
- Williams, with about 930 full-time staff and 1,450 students on campus, tested students twice a week for their first two weeks on campus, then went to weekly tests for about a month. As it loosened some restrictions on student movements—allowing them to travel to a commercial strip with a pharmacy, barber shop and grocery store just east of campus—it returned to twice-weekly tests.
- Since mid-August, when students arrived back on campus, Williams has conducted nearly 23,000 tests. Just 0.022%—five results—have come back positive.
I. Projections & Our (Possible) Future
1. Will the C19 virus become endemic?
- A new article by Columbia Mailman School researchers Jeffrey Shaman and Marta Galanti explores the potential for the C19 virus to become endemic, a regular feature producing recurring outbreaks in humans. They identify crucial contributing factors, including the risk for reinfection, vaccine availability and efficacy, as well as potential seasonality and interactions with other viral infections that may modulate the transmission of the virus. The article appears in the journal Science.
- Shaman is a professor of environmental health sciences and director of the Columbia Mailman School Climate and Health program and a leading authority in modeling infectious disease outbreaks like the coronavirus (SARS-CoV-2) and influenza. He was among the first to recognize the importance of asymptomatic spread and the effectiveness of lockdown measures and published highly cited estimations of the hypothetic lives saved had lockdown occurred sooner. He and Galanti, a post-doctoral research scientist in Shaman’s research group, also published research finding reinfections with endemic coronaviruses are not uncommon, even within a year of prior infection.
- The new paper explores one potential scenario in which immunity to SARS-CoV-2, either through infection or a vaccine, diminishes within a year–a rate similar to that seen for the endemic betacoronavirus that causes mild respiratory illness. The result would be yearly outbreaks of C19.
- On the other hand, if immunity to SARS-CoV-2 was longer, perhaps through protection provided by immune response to infection with other endemic coronaviruses, we might experience what would initially appear to be an elimination of C19 followed by a resurgence after a few years. Other contributing factors include the availability and effectiveness of a vaccine and the innate seasonality of the virus.
- “Should reinfection prove commonplace, and barring a highly effective vaccine delivered to most of the world’s population, SARS-CoV-2 will likely settle into a pattern of endemicity,” the authors write. “Whether reinfections will be commonplace, how often they will occur, how contagious re-infected individuals will be, and whether the risk of severe clinical outcomes changes with subsequent infection remain to be understood.”
- Among those who have been infected with C19, serological studies indicate that most infections, regardless of severity, induce development of some SARS-CoV-2-specific antibodies. Yet it remains unclear whether those antibodies are themselves sufficient to provide long-term “sterilizing immunity” to prevent reinfection. For many viruses, insufficient immune response, waning immunity, or mutations that allow it to “escape” immune detection can undermine or circumvent immunity and allow subsequent reinfection, although a prior infection may provide partial immunity and reduce symptom severity.
- Immune response to SARS-CoV-2 may be affected by whether or not someone is currently or was recently infected with another virus. Many studies prior to the pandemic show that infection with one virus can provide short-term protection–about a week–against a second infection.
- Other studies confirm that simultaneous respiratory virus infections are not associated with increased disease severity. While some SARS-CoV-2 coinfections have been documented, including co-infections with influenza and respiratory syncytial virus, there is insufficient data to draw conclusions. At the population level, a significant seasonal influenza outbreak could strain hospitals already dealing with C19.
- Evidence suggests C19 could be more transmissible during winter. Outside the tropics, many common respiratory viruses reemerge seasonally during particular times of the year. The endemic coronaviruses (OC43, HKU1, NL63, 229E) all exhibit seasonality in temperate regions similar to influenza.
- Similarly, environmental conditions may also modulate SARS-CoV-2 transmissibility–not enough to preclude transmission during the early stages of the pandemic when immunity is generally low but perhaps sufficient to favor recurring seasonal transmission during winter in temperate regions, similar to influenza, once immunity increases.
2. How do pandemics end? History suggests diseases fade but are almost never truly gone
- When will the pandemic end? All these months in, with over 37 million C19 cases and more than 1 million deaths globally, you may be wondering, with increasing exasperation, how long this will continue.
- Since the beginning of the pandemic, epidemiologists and public health specialists have been using mathematical models to forecast the future in an effort to curb the coronvirus’s spread. But infectious disease modeling is tricky. Epidemiologists warn that “[m]odels are not crystal balls,” and even sophisticated versions, like those that combine forecasts or use machine learning, can’t necessarily reveal when the pandemic will end or how many people will die.
- As a historian who studies disease and public health, I suggest that instead of looking forward for clues, you can look back to see what brought past outbreaks to a close – or didn’t.
Where we are now in the course of the pandemic
- In the early days of the pandemic, many people hoped the coronavirus would simply fade away. Some argued that it would disappear on its own with the summer heat. Others claimed that herd immunity would kick in once enough people had been infected. But none of that has happened.
- A combination of public health efforts to contain and mitigate the pandemic – from rigorous testing and contact tracing to social distancing and wearing masks – have been proven to help. Given that the virus has spread almost everywhere in the world, though, such measures alone can’t bring the pandemic to an end. All eyes are now turned to vaccine development, which is being pursued at unprecedented speed.
- Yet experts tell us that even with a successful vaccine and effective treatment, C19 may never go away. Even if the pandemic is curbed in one part of the world, it will likely continue in other places, causing infections elsewhere. And even if it is no longer an immediate pandemic-level threat, the coronavirus will likely become endemic – meaning slow, sustained transmission will persist. The coronavirus will continue to cause smaller outbreaks, much like seasonal flu.
- The history of pandemics is full of such frustrating examples.
Once they emerge, diseases rarely leave
- Whether bacterial, viral or parasitic, virtually every disease pathogen that has affected people over the last several thousand years is still with us, because it is nearly impossible to fully eradicate them.
- The only disease that has been eradicated through vaccination is smallpox. Mass vaccination campaigns led by the World Health Organization in the 1960s and 1970s were successful, and in 1980, smallpox was declared the first – and still, the only – human disease to be fully eradicated.
- So success stories like smallpox are exceptional. It is rather the rule that diseases come to stay.
- Take, for example, pathogens like malaria. Transmitted via parasite, it’s almost as old as humanity and still exacts a heavy disease burden today: There were about 228 million malaria cases and 405,000 deaths worldwide in 2018. Since 1955, global programs to eradicate malaria, assisted by the use of DDT and chloroquine, brought some success, but the disease is still endemic in many countries of the Global South.
- Similarly, diseases such as tuberculosis, leprosy and measles have been with us for several millennia. And despite all efforts, immediate eradication is still not in sight.
- Add to this mix relatively younger pathogens, such as HIV and Ebola virus, along with influenza and coronaviruses including SARS, MERS and SARS-CoV-2 that causes C19, and the overall epidemiological picture becomes clear. Research on the global burden of disease finds that annual mortality caused by infectious diseases – most of which occurs in the developing world – is nearly one-third of all deaths globally.
- Today, in an age of global air travel, climate change and ecological disturbances, we are constantly exposed to the threat of emerging infectious diseases while continuing to suffer from much older diseases that remain alive and well.
- Once added to the repertoire of pathogens that affect human societies, most infectious diseases are here to stay.
Plague caused past pandemics – and still pops up
- Even infections that now have effective vaccines and treatments continue to take lives. Perhaps no disease can help illustrate this point better than plague, the single most deadly infectious disease in human history. Its name continues to be synonymous with horror even today.
- Plague is caused by the bacterium Yersinia pestis. There have been countless local outbreaks and at least three documented plague pandemics over the last 5,000 years, killing hundreds of millions of people. The most notorious of all pandemics was the Black Death of the mid-14th century.
- Yet the Black Death was far from being an isolated outburst. Plague returned every decade or even more frequently, each time hitting already weakened societies and taking its toll during at least six centuries. Even before the sanitary revolution of the 19th century, each outbreak gradually died down over the course of months and sometimes years as a result of changes in temperature, humidity and the availability of hosts, vectors and a sufficient number of susceptible individuals.
- Some societies recovered relatively quickly from their losses caused by the Black Death. Others never did. For example, medieval Egypt could not fully recover from the lingering effects of the pandemic, which particularly devastated its agricultural sector. The cumulative effects of declining populations became impossible to recoup. It led to the gradual decline of the Mamluk Sultanate and its conquest by the Ottomans within less than two centuries.
- That very same state-wrecking plague bacterium remains with us even today, a reminder of the very long persistence and resilience of pathogens.
- Hopefully C19 will not persist for millennia. But until there’s a successful vaccine, and likely even after, no one is safe.
- Given such historical and contemporary precedents, humanity can only hope that the coronavirus that causes C19 will prove to be a tractable and eradicable pathogen. But the history of pandemics teaches us to expect otherwise.
J. Practical Tips & Other Useful Tips
1. What to do about Halloween
- Halloween in America looks extra terrifying this year.
- Coronavirus cases are surging across the country for the third time, and the number of recorded cases in the U.S. just hit eight million. Seventeen states have added more cases in the past week than in any other week of the pandemic.
- So is it safe to trick-or-treat? Is it safe to celebrate Halloween at all?
- Public health experts have warned that going door-to-door for candy could lead to a spike in cases. Several states, including California and Massachusetts, have discouraged trick-or-treating but have not issued an outright ban.
- The CDC issued Halloween safety guidelines that classify traditional trick-or-treating as a high-risk activity, along with indoor haunted houses and crowded costume parties. For safer alternatives, the agency suggests holding costume contests via Zoom, candy scavenger hunts in the home or yard and hosting scary movie nights.
- Still, experts say that there are ways to salvage trick-or-treating, or at least to reduce the considerable risks.
- If you’re planning to head out, avoid large groups and indoor gatherings, and use a face covering (your costume’s mask doesn’t count). Bring hand sanitizer, and while experts say you probably don’t need to sanitize each and every candy wrapper, you should make sure hands are clean before they touch any sweets.
- Dr. Aaron E. Carroll, a professor of pediatrics at Indiana University School of Medicine, suggests in an Opinion article that homeowners place a candy bowl six feet from the door, or on a platter, so children don’t do too much rummaging. Neighborhoods, he adds, can commit to starting earlier so that everyone isn’t all out at once, or even stagger the hours by age groups.
- It’s important to remember that Halloween means a lot to children, especially during a year in which they may not be attending school in person or have had their daily routines upended to the virus.
- “I think completely taking away Halloween could be detrimental to some of the mental health issues that kids are facing right now,” said Dr. Tista Ghosh, an epidemiologist at Grand Rounds, a digital health care company in San Francisco. She added that it’s best to “balance the risk of whatever activity they’re doing with mental health risks as well, and look for ways to minimize risk rather than reduce risk to zero because that’s just not possible.”
- If trick-or-treating is not your thing, here are a few other ways to celebrate the spooky season.
Source: New York Times Coronavirus Briefing
2. Health experts’ Thanksgiving advice in the time of C19: plan, plan, plan
- Anthony Fauci refuses to be cast in the role of the Grinch who stole Thanksgiving.
- But the 79-year-old director of the National Institute of Allergy and Infectious Diseases has let it be known, with a sigh, that his three daughters, who are spread around the country, aren’t coming home for the holiday this year.
- Fauci has emerged as the leading voice urging Americans to take precautions to curb the spread of Covid-19 over Thanksgiving, giving countless interviews and appearing on too many TV shows and podcasts to mention espousing the need to wear masks and practice social distancing. But even he won’t go so far as to tell people not to gather with family for America’s favorite holiday.
- “I think people are going to have to evaluate the level of risk that they want to take, particularly in families in which you have grandpa and grandma and elderly individuals who are going to be vulnerable,” he told STAT during an interview earlier this week. “I’m not making any recommendation about what people should or should not do. The only thing I’m saying, it’s not going to be an easy decision.”
- While Thanksgiving is still six weeks away, people hoping to connect with distant family members are already making anxious plans — and if they aren’t, they should be, public health experts say.
- The most stress-filled travel holiday of the year has taken on whole new dimensions with the emergence of the Covid-19 pandemic. How do you safely get from point A to point B? Does the state you’re traveling to require you to quarantine for two weeks on arrival? Does your home state expect you to quarantine for two weeks on your return? How many generations of family can one safely invite?
- And what to do about Uncle Frank, who dismisses the disease as a “scamdemic” and won’t wear a mask?
- The last question drew no hesitation from the multiple public health experts STAT interviewed for this article. If you are going to get together with family or friends for Thanksgiving in the time of Covid-19, they said, the gathering should be small and made up only of people who share your philosophy about taking precautions to avoid contracting the virus that causes it, SARS-CoV-2.
- “Probably not the best person to bubble with,” Saskia Popescu, an infectious disease specialist and assistant professor in George Mason University’s biodefense program, said of Uncle Frank.
- Another expert, Michael Osterholm of the University of Minnesota’s Center for Infectious Diseases Research and Policy, went where Fauci refused to go.
- People should not be gathering for Thanksgiving with people outside of their immediate households, Osterholm said.
- “We have far too many examples where adult children with grandchildren came home for events over the course of the recent months when seven or eight days later, it’s clear there’s been SARS-CoV-2 transmission,” he said. “And unfortunately, these events far too often end up with one of the people more at risk for severe disease dying. Grandma, mom or dad, aunts or uncles.”
- “It’s happened with weddings. It’s happened with funerals. It’s happened with family reunions. And the holiday season is probably going to be the height of it, because it’s a tradition that is almost sacred,” Osterholm said.
- People who are infected but haven’t yet developed symptoms won’t know, he said. But people who have contracted the virus can infect others in the day or two before their symptoms kick in. By the time you know you’re sick, you may have already infected those around you.
- That’s what happened to Tony Green, a Texas pandemic denier who told the Washington Post recently about a small family gathering that spread Covid throughout his family and the family of his partner, killing his partner’s father and grandmother.
- Most of the experts STAT spoke with view Thanksgiving gatherings as inevitable, and want to ensure people have the information they need to make the get-togethers as safe as possible. Some even see them as important boosts for battered psyches in a year that has tested humanity.
- “I can only speak for myself in saying that I am so tired and feeling very deprived of human connection in many ways,” said Crystal Watson, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health. “And so I understand and I’m feeling the need to see friends and family.”
- Her own parents are in Colorado; they haven’t seen her or her 21-month-old son since the pandemic started. But her in-laws live two states away. Both families have been ultra-cautious and plan to merge their bubbles over Thanksgiving.
- “I think it’s a reasonable thing to do if you take precautions, but it is not going to be worth it if those precautions are not taken, and we ultimately expose especially our older relatives,” Watson said.
- Popescu is sympathetic to the urge.
- “I think it’s tough because, you know, we’re 10 months into this, really,” she said. “There’s a mental health aspect that I think is important not to ignore, you know? And there’s also a safety aspect. So how do we kind of teeter along both of those lines without sacrificing one for the other?” she asked.
- U.S. PIRG, the federation of public interest research groups, has been working on a program called Home Safe for the Holidays. The idea, said Matthew Wellington, director of public health programs, is to give people tools with which to plan and execute family visits over the holidays.
- “This is a big discussion for a lot of families right now,” said Wellington. “So we wanted to tap into that and help people understand what it would take to make that happen.”
- A key to allowing people to safely travel for the holiday to be with family is to get testing in the country to levels where it ought to be, he said. The organization advocates targets set out by Brown University’s School of Public Health.
- Wellington suggested people who want to travel should be haranguing officials in their states to meet the testing targets, starting now. But testing alone isn’t the answer, he acknowledged.
- Those include quarantining, mask-wearing, figuring out the least risky way to get to your destination and limiting the number of people involved.
- “And if there’s someone who is at more risk of severe disease from Covid, then they should consider just gathering virtually rather than getting together physically,” Wellington said.
- Syra Madad, senior director of the system-wide special pathogens program for NYC Health + Hospitals, is working on the Home Safe program with U.S. PIRG. Ideally, she said, people would avoid contact with people outside their direct households this holiday season. But she and others know the reality — “many people are going to do it anyway.”
- Madad suggested people do some homework now. Find out the travel rules for your destination. Plan outdoor events, if the weather allows. Wear masks as much as possible.
- Shorter trips will likely be easier than longer ones. Driving may be safer than flying, though more because of behavior in airports than on airplanes.
- Popescu noted she’s flown a few times recently and was dismayed to see people eschewing eating in airport restaurants, only to crowd into departure lounges to eat take-out food.
- “We know obviously with Covid-19, you have that incubation period. You have a lag of a certain duration until you actually start seeing an uptick in cases and then resulting in hospitalizations and even deaths,” she said. “So I think Thanksgiving is going to certainly set us up for what we’re going to face during Christmas.”
K. Johns Hopkins COVID-19 Update
October 16, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 38.79 million cases and 1.10 million deaths as of 10:00am EDT on October 16.
- In Central America, most countries appear to be holding relatively steady or decreasing in terms of daily incidence. Notably, Mexico and Panama, both hotspots several months ago, have passed their respective first peaks. Mexico’s daily incidence is down 38% from its peak, and Panama’s is down 40%. Mexico remains #1 in the region in terms of total daily incidence, although this is not surprising, considering that Mexico represents more than 70% of the region’s total population.
- On October 9, Mexico reported a large number of cases identified on previous dates, but the average has since returned to its previous trend. On a per capita basis, Costa Rica is reporting 233 daily cases per million population, which leads the region. Costa Rica’s daily incidence increased sharply from mid-to-late June through mid-September, and it has held relatively steady since then. Belize reported a dramatic increase in daily incidence in early August, jumping from 1.3 new cases per day to 49, and its incidence has largely fluctuated between 30 and 50 new cases per day since then. C19 mortality largely follows the incidence trends, with most Central American countries exhibiting decreasing or steady trends, except for Costa Rica and Belize.
- A number of the South American countries that previously exhibited concerning C19 trends have passed their peaks, including Brazil, Colombia, Peru, and Suriname. Brazil remains #1 in South America in terms of total daily incidence, but its average has decreased by 56% since its peak in late July. Colombia recently reported a surge in incidence, but it has declined steadily over the past several days.
- The major exception in South America is Argentina, which is reporting an increase in daily incidence—up to a record high of more than 13,000 new cases per day—and it is #1 in South America in terms of per capita daily incidence (293 daily cases per million population). Guyana is also exhibiting a steady increase in daily incidence, but it remains in the bottom half of South American countries in terms of per capita incidence. Like Central America, the mortality trends in South America are aligned closely with daily incidence.
- The US CDC reported 7.89 million total cases and 216,025 deaths. The daily C19 incidence continues to climb, now up to 52,350 new cases per day, the highest since August 13. Yesterday, the CDC reported 59,761 new cases, the highest daily total since August 7. At this pace, the US could surpass 8 million cumulative cases by tomorrow. The US C19 mortality continues to hold steady at approximately 700 deaths per day.
- More than half of all US states have reported more than 100,000 cases, including California and Texas with more than 800,000 cases; Florida with more than 700,000; New York with more than 400,000; Georgia and Illinois with more than 300,000; and Arizona, New Jersey, North Carolina, and Tennessee with more than 200,000.
- The Johns Hopkins CSSE dashboard reported 8.01 million US cases and 218,097 deaths as of 1:30pm EDT on October 16.
2. WUHAN SEROPREVALENCE STUDY
- Following the world’s first major C19 outbreak, local health officials in Wuhan, China, conducted a city-wide seroprevalence study to determine the extent of community transmission. A study recently published in Clinical Microbiology and Infection described the seropositivity data for more than 60,000 tests conducted in the Wuchang District of Wuhan.
- Among those tested, 1,470 (2.39%) individuals were seropositive for IgM and/or IgG immunoglobulin, indicating prior SARS-CoV-2 infection. Despite the major outbreak in Wuhan— which resulted in a prolonged, highly restrictive “lockdown”— the overall seroprevalence among this population is very low, indicating that the vast majority of residents remain susceptible to the virus. The authors note that many “nonlocal workers” who left Wuhan prior to the lockdown had returned by the time the study was conducted, but many local college and university students had not yet returned, which could have contributed to a slightly lower seroprevalence found in this study. The seroprevalence could vary between communities in Wuhan as well; however, the results from this study are relatively consistent with those from previous studies in other districts.
- Italy is one of many European countries currently facing a resurgence of C19, following a period of relative control. Last week, Italian Minister of Health Roberto Speranza announced that the country was evaluating new social distancing measures in an attempt to curb the spread of disease. The newest restrictions, unveiled on Monday, target social gatherings by restricting gathering in private homes to no more than 6 people; restrict operating hours for restaurants and bars/pubs, including in-person service; limiting receptions following “civil or religious ceremonies” to 30 people; limiting spectators at sporting events, concerts, or other events to 1,000 people for outdoor events and 200 for indoor events; and suspending operations at dance halls and discos.
- Italy is also mandating mask use in public spaces, including indoors and outdoors and requiring travelers arriving from several European countries—Belgium, the Czech Republic, France, the Netherlands, the UK, and Spain—to provide documentation of a recent negative molecular or antigen test or undergo testing at the point of entry or local health authority within 48 hours of arrival (and self-isolate until the results are available).
4. UNITED KINGDOM
- As cases and deaths continue to increase in the UK, government officials are implementing increasingly restrictive measures to contain transmission. Following the announcement by UK Prime Minister Boris Johnson that England will implement a 3-tiered system of social distancing measures, some parts of the country are moving into highly restrictive “lockdowns.” The 3-tiered system—which categorizes localities into Medium, High, and Very High Alert Levels—outlines specific restrictions based on the current SARS-CoV-2 transmission risk.
- The most restrictive level, Very High, largely prohibits or severely restricts social interaction between households or “bubbles.” Restaurants and pubs are limited to delivery or pick-up/takeaway service only (i.e., no in-person dining), and households and bubbles are only permitted to interact with one another outdoors—and even in that case, they are limited to 6 total people. Violations can lead to fines, including up to £10,000 (US$13,000) for gatherings of 30 people or more. According to media reports, the UK government is under pressure to implement “circuit breaker” measures—a short-term, highly restrictive lockdown that aims to drive large-scale interruption of community transmission—in an effort to rapidly contain the current resurgence before the country enters influenza season. Other countries have implemented similar short-term “circuit breaker” plans, including Singapore in April and May.
- The government in Northern Ireland is strengthening restrictions to curb transmission. In addition to existing restrictions, “bubbles” will be limited to 10 total people, in-person service at restaurants will be prohibited after 11pm, most gatherings will be limited to 15 people, and alcohol sales at supermarkets and some other businesses will be restricted after 8pm. Funerals and wedding ceremonies will be permitted to include 25 attendees, but wedding receptions will be prohibited. These restrictions are scheduled to remain in place for 4 weeks.
- The Welsh government is also implementing enhanced restrictions in response to its C19 surge. Much like England, Wales is implementing a series of ”local lockdown” restrictions. In addition to the local social distancing measures, Wales is also restricting travelers from other parts of the UK. Individuals “living in areas with a high-prevalence of coronavirus in England, Scotland and Northern Ireland” will be prohibited from traveling “to parts of Wales where there is a low prevalence.” Reportedly, the Welsh government is also considering a “circuit breaker” or “fire-break” approach, which could last several weeks, in order to bring the epidemic under control. The plan is still under evaluation, but it could potentially be announced as early as Monday.
5. YOUTUBE BANS C19 VACCINE MISINFORMATION
- The social media platform YouTube is banning misinformation related to C19 vaccines. YouTube has long been criticized for a culture that allows for the spread of misinformation, including on the C19 pandemic, but the recent announcement indicates that the platform will take a tougher stance against content that contradicts evidence-based statements by the WHO or other legitimate health agencies. The announcement cited several examples of prominent C19 vaccination rumors to illustrate the type of material that would be targeted under the platform’s C19 Medical Misinformation Policy. A spokesperson for YouTube said that the platform would allow videos that shared “broad concerns” regarding potential future C19 vaccines, but not information that contradicts evidence-based information from reliable health sources.
6. BLOOD TYPES
- Two recent studies—both published in Blood Advances, an open-access journal from the American Society of Hematology—provide evidence that an individual’s blood type (or blood group) could be a factor in their risk of SARS-CoV-2 infection or severe C19 disease. The first study was conducted by researchers in Denmark, who found that SARS-CoV-2 infection prevalence was significantly lower among individuals with type O blood, compared to other blood groups. The study included data from all patients tested for SARS-CoV-2 in Denmark between February 27 and July 30—more than 450,000 individuals, including nearly 7,500 cases—as well as 2.2 million non-tested individuals (approximately 38% of the entire Danish population) to serve as a reference population.
- The researchers found that individuals with type O blood represented 41.69% of the reference population but only 38.41% of positive SARS-CoV-2 tests. Individuals with types A and AB represented a significantly higher proportion of positive cases than the reference population—44.41% vs 42.73% and 5.09% vs 4.46%, respectively. Previous research has demonstrated that anti-A antibodies present in type O blood are capable of glycosylating the SARS-CoV-1 virus, and the researchers theorize that this could be possible for the SARS-CoV-2 virus as well, which could potentially physiological basis for the disparities between the various blood types. The study did not find a significant association between blood type and severe C19 disease or death.
- The second study—conducted by researchers in Vancouver, Canada—found a significant association between blood groups and C19 disease severity. In contrast to the study above, this study was much smaller. The researchers included data from 95 hospitalized C19 patients, but the distribution of blood groups among the patients was relatively representative of the national and provincial populations. The researchers found that patients with type A and AB blood were more likely to require mechanical ventilation and continuous renal replacement therapy and had longer admission times in an intensive care unit, compared to patients with types B and O blood.
- Previous studies on associations between C19 and blood type have been published with mixed results. For example, one study conducted in Boston, Massachusetts (US), found no link between blood type and disease severity. The researchers did find a potential association with SARS-CoV-2 infection, but only among Rh positive individuals. Another study, conducted in New York City, found a decreased risk of infection among individuals with type O blood, compared to all other types. The researchers also found a decreased risk of intubation among individuals with type A blood and decreased risk among those with types AB/B blood, compared to type O.
7. LONG-TERM HEALTH EFFECTS
- The UK National Institute for Health Research published a review of scientific literature on long-term, “ongoing” C19 disease, also referred to by some as “long Covid.” A unique feature of this report is that the researchers included both an expert steering group, composed of clinicians and other experts, and direct input from patients experiencing long-term effects following SARS-CoV-2 infection. The report notes that while much of the attention about C19 has focused on acute illness and mortality, there is growing evidence of the long-term health effects of C19.
- There is currently a lack of consensus on how to define and diagnose these long-term effects, which can vary widely in presentation and severity between patients, including fatigue, difficulty breathing, and chest pain. Additionally, the types of symptoms and severity can fluctuate over time and affect multiple organs, including the lungs, heart, kidneys, and brain.
- The researchers believe that ongoing C19 may actually be a combination of 4 syndromes, rather than one underlying condition, and that symptoms in one organ system can subside and then emerge in other organ systems. The 4 syndromes identified include: (1) permanent damage to the lungs and heart, (2) post-intensive care syndrome, (3) post-viral fatigue syndrome, (4) and continuing C19 symptoms. Patients experiencing these syndromes spanned the spectrum of acute disease severity, from mild to severe, as well as individuals who were not ill enough to be tested during their acute infection.
8. CRISPR DIAGNOSTIC TEST
- Research and development continues on a variety of rapid, point-of-care tests for SARS-CoV-2. Researchers at the Institute of Genomics and Integrative Biology in New Delhi, India, developed a CRISPR-based testing assay that exhibits comparable sensitivity and specificity to the gold standard PCR-based diagnostic tests—96% and 98%, respectively—while providing faster results and eliminating the need for associated specialized equipment. Key advantages of the test include that it can be conducted more rapidly than the gold standard qPCR diagnostic assays, in as little as 1 hour.
- The test, named FELUDA (after a fictional Indian detective), does require a nasopharyngeal swab and a RT-PCR process, but it does not require the expensive equipment or advanced training necessary to conduct traditional quantitative PCR-based diagnostic tests. Gold nanoparticles in the test strip cause it to change color for positive tests, providing easy-to-read visual indication for the user. The test could be usable in a variety of settings, including in low-resource settings or the point of care, and the company also indicated that it is working on developing a test kit for at-home use. This test is conceptually similar to the SHERLOCK test developed at MIT (Massachusetts, US)—also named after a fictional detective—which received an Emergency Use Authorization from the US FDA in May.
9. HERD IMMUNITY
- The Great Barrington Declaration, a document that argues for a deliberate effort to develop herd immunity to SARS-CoV-2 through natural infection by encouraging lower-risk individuals to resume normal activity, has faced substantial opposition from health experts. Several groups of experts have published opposition statements. Perhaps most notably, The John Snow Memorandum, originally published in The Lancet, outlines the current evidence-based understanding of SARS-CoV-2 transmission and effective protective measures. The memo emphasizes that “uncontrolled transmission in younger people risks significant morbidity and mortality across the whole population” and threatens to “overwhelm the ability of healthcare systems.”
- A separate but related effort by 14 highly respected public health and health security organizations, including the Johns Hopkins Center for Health Security, condemns the Barrington Declaration and the associated herd immunity strategy as dangerous. The organizations argue that the Barrington Declaration “ignores sound public health expertise” and that the “suggestions put forth…are NOT based in science” (emphasis in original). They also emphasize that “lockdowns” and “full reopening” are not binary choices. Protective measures exist along a spectrum, and multiple complementary policies can provide meaningful protection while enabling individuals to resume some semblance of normal activity. They also note that protecting health and economic security are not mutually exclusive. Rather, they are interdependent, and responsible and effective C19 strategies support both.
10. C19 & CRIMINAL JUSTICE
- The Johns Hopkins Center for Health Security, in collaboration with a number of other experts from the Johns Hopkins University Bloomberg School of Public Health, published a report on C19 and the US criminal justice system. As we have covered previously, incarcerated populations have been identified as being at elevated risk of C19 outbreaks as well as severe disease and death. These vulnerable populations live in prolonged close contact with others, have high rates of underlying health conditions, and often face systemic discrimination, including for race, physical disability, mental health issues, and financial insecurity. This report, supported by the National Commission on C19 and the Criminal Justice System, provides an overview of the impacts of C19 on incarcerated populations and provides recommendations for mitigating these risks. The findings focus heavily on reducing population and population density in carceral facilities and improving infection control practices.
- The recommendations range from improving testing capacity, quarantine and isolation strategies, and clinical care for incarcerated populations to rethinking how the criminal justice system addresses physical and mental health issues, including substance abuse, in order to reduce the overall number of incarcerations. The authors also call for including incarcerated populations and staff working at carceral facilities among priority populations for vaccination due to the increased C19 risk.