Coronavirus Update

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Coronavirus Update 8-25

Recent Developments & Headlines

August 25, 2020

“Lockdown was a panic measure and I believe history will say trying to control C19 through lockdown was a monumental mistake on a global scale, the cure was worse than the disease.  I believe the harm lockdown is doing to our education, health care access, and broader aspects of our economy and society will turn out to be at least as great as the harm done by C19.  I never want to see national lockdown again.”  

Mark Woolhouse, top British epidemiologist on the UK’s official panel of C19 advisors and professor at the University of Edinburgh

Index

A. The Pandemic As Seen Through Headlines

B. Numbers & Trends

1. Cases & Tests

2. Deaths

3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity 

C. New Scientific Findings & Research

1. Not just antibodies: B cells and T cells mediate immunity to C19  (*)

2. New guidelines say coronavirus antibody tests are pointless   (!)

3. First C19 reinfection documented  (*) 

4. To Test Spread of C19, Scientists Put on a Concert  

5. Researchers discover immune predictors of C19 cases that fare the worst  

6. Severe viral infection overwhelms immune cells  

7. Why C19 infection curves behave so unexpectedly  

D. Vaccines & Testing

1. 9 reasons to be optimistic that a C19 vaccine will be widely available in 2021

   2. A Vaccine That Stops C19 Won’t Be Enough  

3. New Low-Cost, Accurate C19 Antibody Detection Platform Developed 

4. Do-it-yourself coronavirus testing sparks kudos, and caution  

E. Improved & Potential Treatments

1. Roche to partner with Regeneron on C19 treatment 

2. Hepatitis Drugs May Be Effective C19 Treatment  

F. Concerns & Unknowns

1. C19 Medical Mystery: Patients Come Off Ventilator But Linger In Coma  

G. The Road Back?

1. New Thinking on Covid Lockdowns: They’re Overly Blunt and Costly 

H. Back To School!?

1. Updated CDC School Guidance 

I. Advances in Technology & Equipment

1. Reusable mask is designed to fix the 28 major problems with the N95  

J. Practical Tips & Other Useful Information

1. It’s Not Enough to Wear a Mask, You Have to Wear It Right 

K. Johns Hopkins COVID-19 Update (8/24)

L. Links to Other Stories

  • Dangers of oleandrin  Toxicology Organizations issued joint statement regarding dangers of proposals for the use of a potential treatment for C19
  • How the Hamptons crowd partied this summer Determined to proceed with parties and events this summer, hosts are adding screenings at the door. Guests would test before events, sometimes to the cost of $500 per test
  • What Happened in Room 10?  Inside the first Covid hotspot in America. Forty-six people associated with the nursing home died, exposing how ill-prepared we were for the pandemic — and how we take care of our elderly

A. The Pandemic As Seen Through Headlines

(In no particular order)

  • Feds to impose new coronavirus testing rules after New York nursing home fiasco
  • Quarantine rules are expanding around the world, but not in America
  • Texas cases top 600,000
  • Florida tops 600,000 cases; new cases, hospitalizations fall
  • US deaths below 1,000
  • Florida, Arizona see new cases fall to lowest levels in months
  • California cases, hospitalizations decline
  • Worst death tolls are in Democrat-run states
  • Why are the numbers of U.S. cases decreasing? Because restrictions are working, experts say.
  • The city of Danbury in Connecticut is facing a “serious outbreak” of the coronavirus, officials urged residents to stay home
  • India reports more than 61,000 new cases
  • South Korea reports 266 new cases, highest since March
  • South Korea on verge of ‘massive’ nationwide COVID-19 outbreak
  • The virus is found to be circulating in Gaza
  • China reports 16 new ‘imported’ cases
  • A 40-day lockdown in western China prompts anger and anxiety
  • Victoria reports 116 new cases
  • India passes 3 million cases
  • COVID has “fundamentally changed” Sweden, PM says
  • Germany issues travel warning for Paris area
  • At Least 13 Killed In Peru Nightclub Stampede Triggered By Police ‘Social Distancing’ Raid
  • Advisor To British Government Warns Coronavirus “Might Be With Us Forever”
  • Bali postpones its plan to begin allowing foreign tourists.
  • Connecticut school district to begin year online amid ‘serious’ COVID-19 outbreak
  • A judge struck down a state order requiring most Florida schools to open for in-person instruction
  • University of Alabama records more than 500 coronavirus cases in less than a week
  • US faces back-to-school laptop shortage amid COVID-19
  • Zoom fixes partial outages that disrupted the first day of virtual classes for many U.S. students
  • NY to allow some high school sports to start late next month
  • There is no dancing allowed in New York’s bars and restaurants, even at a wedding reception, according to NY State Liquor Authority.
  • To control the spread of the coronavirus, NY Gov. Andrew Cuomo’s liquor authority has banned darts, pool, cornhole, karaoke and exotic dancing

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.  Green highlights indicate a decrease or no change and yellow highlights indicate an increase. 

Sources: https://www.worldometers.info/coronavirus/ and https://covidtracking.com/

1. Cases & Tests

Worldwide Cases:  
  • Total Cases = 23,802,872 (+0.9%)
  • New Cases = 213,609 (-4,744) (-2.2%)
  • New Cases (7 day average) = 249,388 (+2,158) (+0.9%)
Observations:
  • 7 day average of new cases has generally been trending lower since 8/14, but have ticked up slightly the last 2 days
  • Almost 1,000,000 cases every 4 days (based on 7 day average)
US Cases & Testing: 
  • Total Cases = 5,915,630 (+0.7%)
  • New Cases = 41,484 (+8,766) (+26.8%)
  • Percentage of New Global Cases = 19.4%      
  • New Cases (7 day average) = 43,226 (+91) (+0.2%)
  • Total Number of Tests = 76,883,479 
  • Percentage of positive tests (7 day average) = 6.4% 
Observations:
  • 7 day average of new cases has been generally declining since 7/25 (2nd peak)
  • 7 day average of new cases has declined by 37.6% since 7/25
  • 7 day average percentage of positive tests continues to trend lower

2. Deaths

Worldwide Deaths: 
  • Total Deaths = 816,574 (+0.5%) 
  • New Deaths = 4,350 (+69) (+1.6%)
  • New Deaths (7 day average) = 5,608 (+7) (+0.1%)
Observations:
  • 7 day average of new deaths has been trending lower since 8/13
US Deaths: 
  • Total Deaths = 181,114 (+0.3%)
  • New Deaths = 510 (+80) (+18.6%)
  • Percentage of Global New Deaths = 11.7% 
  • New Deaths (7 day average) = 980 (-9) (-0.9%)
Observations:
  • 7 day average of new deaths has been generally declining since 8/4 (2nd peak)
  • 7 day average of new deaths falls below 1,000 for the first time since 7/28

3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (8/24)

ChartChart
ChartChart
Observations:
  • Continued decline in cases throughout the US
    • New cases less than 40,000 for the 2nd straight day and the lowest level since June 23
    • Florida and Texas new cases reach their lowest level since June 15
  • Daily deaths appear to have peaked in most of the sunbelt states during the 2nd week of August.
    • The 7-day average number of deaths in Florida have declined 32% off their previous high on Aug 16
    • Georgia average daily deaths over the last week have declined 16% from the previous high on Aug 13
    • California and Texas daily deaths are falling, but remain persistently high, averaging 130 and 194 deaths per day, respectively, over the past week

Source: Worldometer and The Covid Tracking Project

C. New Scientific Findings & Research

1. First C19 reinfection documented 

  • Researchers in Hong Kong on Monday reported what appears to be the first confirmed case of C19 reinfection, a 33-year-old man who was first infected by coronavirus in late March and then, four and a half months later, seemingly contracted the virus again while traveling in Europe.
  • The case raises questions about the durability of immune protection from the coronavirus. But it was also met with caution by other scientists, who questioned the extent to which the case pointed to broader concerns about reinfection.
  • There have been scattered reports of cases of C19 reinfection. Those reports, though, have been based on anecdotal evidence and largely attributed to flaws in testing.
  • But in this case, researchers at the University of Hong Kong sequenced the virus from the patient’s two infections and found that they did not match, indicating the second infection was not tied to the first. There was a difference of 24 nucleotides — the “letters” that make up the virus’ RNA — between the two infections.
  • “This is the world’s first documentation of a patient who recovered from C19 but got another episode of C19 afterwards,” the researchers said in a statement.
  • Experts cautioned that this patient’s case could be an outlier among the tens of millions of cases around the world and that immune protection may generally last longer than just a few months. They said that ongoing studies tracking patients who had recovered from C19 would help reach more definitive conclusions. They also noted that the man’s second case was milder than his first, indicating that his immune system was providing some level of protection, even if it could not prevent the infection entirely.
  • “There’s been more than 24 million cases reported to date,” Maria Van Kerkhove, a coronavirus expert at the World Health Organization, said at a briefing Monday, when asked about the Hong Kong report. “And we need to look at something like this at a population level.”
  • The question of how long someone is protected from C19 after being infected and recovering looms large.
  • Studies are increasingly finding that most people who recover from the illness mount a robust immune response involving both antibodies (molecules that can block the virus from infecting cells again) and T cells (which can help clear the virus). This has suggested that people would be protected from another case for some amount of time.
  • But based on what happens with other coronaviruses, experts knew that immunity to the coronavirus would not last forever. People generally become susceptible again to the coronaviruses that cause the common cold after a year or even less, while protection against SARS-1 and MERS appears to last for a few years.
  • “What we are learning about infection is that people do develop an immune response, and what is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” Van Kerkhove said. She added she was still reviewing the Hong Kong case.
  • The strength and durability of the immune response is also a crucial factor in how long vaccines will be effective for, and for how often people might need a booster dose.
  • In the Hong Kong case, the man had traveled to Spain and returned to Hong Kong via the United Kingdom. A saliva sample was taken upon arrival in Hong Kong as part of a screening protocol and tested positive for coronavirus on Aug. 15.
  • During his second infection, the man did not have any symptoms. Some patients go through their course of C19 without showing symptoms, but researchers have also hypothesized that secondary cases of the coronavirus will generally be milder than the first. Even if immune systems can’t stop the virus from infecting cells, they might still rally some level of response that keeps us from getting sicker. During his first case, the patient had classic C19 symptoms of cough, fever, sore throat, and headache.
  • Experts said it was also important to consider the immune response the patient generated after his first infection. While most people seem to mount a solid response, there has been indication that some people do not produce neutralizing antibodies — those that can block the virus from infecting cells — at very high levels, for unclear reasons.
  • “The fact that somebody may get reinfected is not surprising,” said Malik Peiris, a virologist at the University of Hong Kong, who is not an author of the paper describing the reinfection but is familiar with the case. “But the reinfection didn’t cause disease, so that’s the first point. And the second thing is that it is important to know whether the patient mounted a neutralizing antibody response to the first infection or not. Because the vast majority of patients in our experience do mount a good neutralizing antibody response. So is this person an outlier or is he likely to be the average person infected?”
  • Even if the Hong Kong case is an outlier, it points to a few implications: For one, people who have recovered from C19 should also be vaccinated, the researchers said. And they should continue following precautions like wearing a mask and physical distancing.

Source: First Covid-19 reinfection documented in Hong Kong, researchers say

2. New guidelines say coronavirus antibody tests are pointless  

  • You’ve heard about them everywhere since the beginning of the health crisis; antibody tests that can tell you whether you’ve had an undiagnosed C19 case in the past and whether you might be immune to the illness. Apply that concept to an entire community and you can determine the real rate of C19 penetration. 
  • Studies from Spain and comments from the CDC said in the past few months that the actual infection figure might be close to 10 times higher than what has been reported. Antibody tests are also needed in vaccine trials, to prove whether the immune system has started raising armies of antibodies that might block the virus once the real thing comes along.
  • But recent studies have shown that antibodies wane in time and they might disappear from the bloodstream entirely within three months. C19 immunity isn’t lost when that happens, as hordes of T cells retain a memory of the infection and can help kill the pathogen upon reinfection. Studies also showed that current antibody tests could give false-negative results in patients who had C19 in the past.
  • This all brings us to new guidelines that say antibody tests are pretty much pointless for individuals, although there are instances where they may be useful.
  • The Infectious Disease Society of America (IDSA) published an extensive paper on C19 serologic testing.
  • The organization found that antibody testing isn’t good enough to “determine immunity or risk of reinfection.” The tests “cannot inform decisions to discontinue physical distancing or lessen the use of personal protective equipment.” That’s a more complex way of saying that you’re out of luck if you’re trying to determine whether that cold or flu-like illness back in February of March was really C19. 
  • Another implication is that the so-called immunity passports that people keep talking about are completely out of the question. If current antibody testing isn’t good enough to prove someone had C19, they can’t be used for issuing any sort of documentation that would say as much. And antibody testing is the only way hospitals can quickly check C19 immunity right now. T cell and B cell testing is far more complicated and not as widely available.
  • The IDSA panel does think that antibody tests have a few limited uses, including one that somewhat contradicts the previous point. The society says that antibody tests can be used in epidemiological studies looking at herd immunity in communities. But if antibody tests can’t detect older infections, as we’ve just established, those herd immunity studies might not paint an accurate picture of a city or country’s C19 immunity. Tests could pick up patients who were recently infected but might miss others, which is precisely what a recent study showed. Therefore, such research would always deliver a lower percentage of immunity in a community.
  • IDSA says there are two clinical scenarios where antibody testing has potential utility. One involves the “evaluation of individual patients with a high clinical suspicion for C19” who keep testing negative, or who do not have access to PCR tests. But even this sort of use might not always yield accurate results. The paper notes there may be issues with antibody tests that could hinder that work:
    • In general, IgM tests tend to have lower sensitivity to detect past infection than IgG or total antibody tests. Assays designed to detect and differentiate IgM and IgG in combination, where the detection of either IgM or IgG is used to define a positive test result and IgA tests tend to have lower specificity to detect past infection compared to IgG only or total antibody tests.
  • IgM, IgG and IgA are types of Y-shaped immunoglobulins, or antibodies. IgM antibodies appear later in C19 than with other viruses, IgG antibodies are detectable two weeks after infection and IgA antibodies aren’t as good as telling SARS-CoV-2 apart from other human coronaviruses.
  • The paper also notes that the sensitivity and specificity of IgG and total antibody counts are optimal three to four weeks after the onset of symptoms. By the time antibody tests are optimal, people who are suspected of having been infected might have already cleared the virus.
  • There is a third instance where serological testing might be useful and that’s the “for assessments of suspected multisystem inflammatory syndrome in children.” That’s the MIS-C syndrome that some kids experience, which could be fatal.
  • Not all hope is lost for using antibody tests for mapping out C19 immunity. But tests should have a high clinical sensitivity and specificity (over 99.5 percent) “to be of value.” Antibody test makers should come up with improved test kits that would have very low false-negative and false-positive results. Right now, it’s believed that many antibody tests are not accurate. 
  • Even for herd immunity studies, the ISDA panel advises that tests should be correctly positive 96% of the time and correctly negative at least 99.5% of the time. The majority of test kits that the panel studied do not meet these standards, Dr. Angela Caliendo told The New York Times. Also, none of them are available for at-home testing. The best types of antibody tests are Elisa or CIA (chemiluminescence immunoassay), so that’s the kind of serological testing you should be looking for.
  • One of the problems with antibody tests in America is the FDA’s decision to approve them without reviewing safety and efficacy data. That decision was reversed in May, with the FDA giving test-makers 10 days to prove their assays were accurate. 
  • But on Wednesday, the Department of Health and Human Services said that labs that made their tests did not have to go through an FDA review anymore, per an executive order from Trump. The order does not apply to commercial tests, but the tests you can buy right now are still not good enough.

Source: New guidelines say coronavirus antibody tests are pointless 

3. Not just antibodies: B cells and T cells mediate immunity to C19 

  • C19 is caused by infection with SARS-CoV-2, which is a member of the coronavirus family. There are currently four human coronaviruses (HCoVs) that cause respiratory infections or the ‘common cold’ (namely, 229E, NL63, OC43 and HKU1), as well as three coronaviruses that have arisen through zoonosis and cause severe diseases in humans, namely, SARS-CoV, MERS-CoV and SARS-CoV-2, which emerged in 2003, 2012 and 2019, respectively. 
  • Immunity after infection with the coronaviruses may last from months to several years. Interestingly, cross-reactive immune responses to HCoVs may be boosted after severe infection; 12 of 20 patients infected with SARS-CoV had at least fourfold increases in IgG that cross-reacted with OC43 and/or 229E HCoVs2. It is still unclear how long immunity to SARS-CoV-2 lasts after recovery from infection. A recent report suggesting that antibodies to the virus may only be maintained for 2 months has caused speculation that ‘immunity’ to the virus may not be long lived. Similarly, a rapid decline in antibodies was reported in mild cases, although with a half-life of approximately 21 days for IgG we would expect this decrease. 
  • It is important to remember that memory B cells and T cells may be maintained even if there are not measurable levels of serum antibodies. Below, we outline our current understanding of B cell and T cell immunity to SARS-CoV-2 and potential immune correlates of protection that could inform vaccine efficacy studies (Fig. 1).

Fig. 1: T cells and B cells in immunity to SARS-CoV-2.

figure1

a | Infection with SARS-CoV-2 leads to activation of innate immunity and dendritic cells (DCs), which will drive the induction of virus-specific T cell and B cell responses. Little is currently known concerning the memory response to SARS-CoV-2, but this will be important for developing an effective vaccine. 

b | A predicted time-course of adaptive immunity to SARS-CoV-2. CTL, cytotoxic T lymphocyte; TFH, T follicular helper cell; TH, T helper cell; Treg, regulatory T cell.

  • Infection with SARS-CoV-2 induces diverse outcomes, ranging from a large proportion of asymptomatic infections to fulminant pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure and death. 
  • Although SARS-CoV-2 infection induces antibody responses, antibody levels may be dependent upon the severity of disease and the virus inoculum. Upon viral clearance, there will no longer be stimulation and proliferation of new B cells. IgG and IgM antibodies have been found in asymptomatic individuals who tested positive for SARS-CoV-2, but these antibodies were present at markedly lower levels than in patients with COVID-19 (ref.5); these findings need to be confirmed in larger studies. Antibodies to the spike protein and its receptor-binding domain (RBD) are the main target for neutralizing antibodies as they prevent the virus binding to epithelial cells in the airway through its entry receptor ACE2. 
  • Potent neutralizing antibody responses have been found in hospitalized patients with C19, and human monoclonal antibodies (mAbs) generated from these patients target multiple epitopes of the spike protein and could be a promising therapy. These neutralizing antibodies did not show extensive somatic hypermutation, which is encouraging for development of spike-protein-based vaccines. Furthermore, treatment with convalescent plasma therapy in severely ill patents is reported to reduce mortality. However, we do not yet know the durability of the antibodies induced by SARS-CoV-2 or the antibody titres that will protect against reinfection; variations in laboratory methodology may make this even more complex to determine.
  • The induction of SARS-CoV-2-specific memory T cells and B cells (as opposed to circulating antibodies) is important for long-term protection. In particular, T follicular helper (TFH) cells indicate maturation of the humoral immune response and the establishment of a pool of specific memory B cells ready to rapidly respond to possible reinfection. 
  • SARS-CoV-2-specific T cells are recruited from a randomly formed and pre-constituted T cell pool capable of recognizing specific viral epitopes. Specific CD4+ T cells are important for eliciting potent B cell responses that result in antibody affinity maturation, and the levels of spike-specific T cells correlate with serum IgG and IgA titres. Robust immune responses with spike-specific neutralizing antibodies, memory B cells and circulating TFH cells have been found in patients who have recovered from C19 infection. 
  • Although spike-specific CD4+ T cells are found in patients with C19, 30–50% of healthy people with no detectable C19 infection also had SARS-CoV-2-specific CD4+ T cells and 20% had CD8+ cytotoxic T cells. These T cells are probably cross-reactive with other HCoVs, but whether they can provide protection from C19 disease remains to be determined. 
  • Furthermore, CD4+ T cells and CD8+ T cells specific for SARS-CoV-2 were found in the convalescent phase after mild C19 and these T cells were shown to recognise peptides derived from the viral spike, nucleoprotein and matrix as well as other viral proteins. As we learn more about the multifaceted immune response to SARS-CoV-2 virus, we will begin to understand the correlates of protection and how pre-existing immunity to HCoVs may impact upon the outcome of infection.
  • Lymphopenia with reduced numbers of CD4+ and CD8+ T cells is a hallmark of severe C19 disease, often associated with exhausted T cells with less proliferative ability and increased levels of pro-inflammatory cytokines. Studies of patients who became infected with SARS-CoV in 2003 suggested that the infection induced durable T cell responses lasting for 6 years but no long-term memory B cells. Importantly, these T cells were shown to cross-react with the SARS-CoV-2 virus 17 years later, but the extent to which they can provide protection is not known. Most importantly, the early global sharing of scientific data is vitally important to understand the complexities of the B cell and T cell responses in C19 and to elucidate which immune responses provide protection from both the initial infection and reinfection.
  • Many vaccines are currently being developed and the lessons learnt from development of SARS-CoV and especially MERS vaccines have provided an advantage for rapid development of candidate vaccines for SARS-CoV-2. Encouraging results, often measuring antibody responses, have been reported from several versatile vaccine platforms (for example, nucleic acid and virus vector vaccines), and these vaccines have now entered later stage human clinical trials. 
  • During the swine influenza pandemic of 2009, the first vaccines were available within 6 months in the Western world based on seasonal influenza vaccine production. As there are no licensed CoV vaccines and with the urgency of the ongoing pandemic, controlled human challenge experiments of young healthy volunteers to identify correlates of protection may be necessary to speed up the evaluation of vaccines and to provide definitive data on which immune responses provide durable protection. Ultimately, we will need to harness immune memory responses to develop effective vaccines, which must be made available to people in all regions of the word in order to bring the pandemic under control.

Source: Not just antibodies: B cells and T cells mediate immunity to COVID-19

4. 56 people got the coronavirus at a Starbucks in South Korea. The only people who didn’t were employees wearing masks.

  • At least 56 cases of the novel coronavirus in South Korea have been traced back to a Starbucks location in the city of Paju. Many customers were not wearing masks, and the poorly ventilated space likely contributed to the spread of the virus, according to local news. 
  • But employees at the business were not infected, and experts believe it’s because they were wearing masks.
  • Health officials said the outbreak originated from a single person infected with the virus who sat in the cafe next to the air conditioning system, which dispersed contagious aerosol particles throughout the space, according to Arirang News. The virus could also have spread as people touched contaminated surfaces such as tables and door handles, they said. 
  • “Many of the visitors didn’t wear masks, and there seems to be no proper air ventilation at the store even though air conditioners were in operation due to humid weather,” Korea Centers for Disease Control and Prevention (KCDC) chief Jeong Eun-kyeong said of the outbreak, according to local media. “Even if infections did not occur via aerosol transmission, droplet transmission is also possible in a confined space, and the virus could have spread via hand contact.”
  • The four employees working during the shift were not infected. Health officials said it’s because staff consistently wore masks for the duration of their work hours. 

Source: 56 people got COVID-19 in South Korea Starbucks, mask-wearers did not

5. Researchers discover immune predictors of C19 cases that fare the worst  

  • Mount Sinai scientists have identified two markers of inflammation that reliably predict the severity of C19 cases and likelihood of survival, providing a foundation for a diagnostic platform and therapeutic targets, according to a study published in Nature Medicine in August.
  • The researchers studied 4 proteins known as cytokines that circulate in blood and are commonly associated with infections, and found that two of them, called IL-6 and TNF-α, were able to predict which patients were likely to develop more severe forms of C19 and die. 
  • The scientists established that the levels of IL-6 and TNF-α in serum, when measured at admission to the hospital, were elevated in patients who fared the worst, a finding that was independent of the patients’ other underlying medical conditions, of demographics such as age and sex, and of other standard clinical biomarkers of disease severity such as low blood oxygen saturation and common markers related to inflammation, iron levels, and blood clotting issues.
  • This study suggests that these cytokines should be monitored in the treatment of C19 patients to help select those who should enter clinical trials and receive specific drugs that can target them, the researchers say.
  • “We propose that serum IL-6 and TNF-? levels should be considered in the management and treatment of C19 patients to stratify prospective clinical trials, guide resource allocation, and inform therapeutic options,” said lead researcher Sacha Gnjatic, PhD, Associate Director of the Human Immune Monitoring Center at Mount Sinai; Associate Professor of Medicine, Oncological Sciences and Pathology, at the Icahn School of Medicine at Mount Sinai; and a member of the Precision Immunology Institute and The Tisch Cancer Institute at Mount Sinai. “We also propose that patients with high IL-6 and TNF-? levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease. Drugs blocking these cytokines are either FDA-approved or in clinical trials.”
  • When the pandemic began, Mount Sinai scientists promptly implemented a rapid test to measure the levels of four cytokines associated with pathogenic inflammation, which were suspected to cause severity in C19 patients. In just one month, cytokine blood levels were tested in 1,484 patients upon admission to Mount Sinai Health System’s hospitals, and patients were followed for up to 41 days.
  • Thanks to an emergency authorization from the New York State Department of Health, the test was allowed to be placed in the hospital’s electronic medical record system where doctors order standard blood tests and medicines for patients, allowing for the rapid collection of a large amount of samples. Results were available in three hours, leading researchers to believe it could be implemented in a clinical setting to stratify patients and determine treatments in almost real time.
  • The results from the tests showed that the risk of death in patients with elevated IL-6 or TNF-α was twofold or higher, even when considering other known risk factors. Scientists then validated their predictive model using samples from an additional cohort of 231 hospitalized C19 patients.
  • The researchers looked at how various treatments attempted in a subset of these patients affected the cytokines they measured. They found that treatments recently found to benefit C19 patients, such as the antiviral remdesivir or the corticosteroid dexamethasone, could lower the levels of the cytokines.
  • Based on these results, scientists propose that monitoring C19 patients for these cytokines can help determine their prognosis, and that any treatment should be potentially administered in the context of cytokine measurements, since it affects outcome.
  • The researchers propose that these findings also call for the use of drugs targeting IL-6 and TNF-α by themselves or combined at the same time, to be tested for their potential benefit based on elevated starting levels.
  • Monitoring the levels of IL-6 and TNF-a before and during experimental treatments such as anti-cytokine antibodies or corticosteroids will be useful to establish a predictive and prognostic value for these potential biomarkers.

Source: Researchers discover immune predictors of COVID-19 cases that fare the worst 

6. Severe viral infection overwhelms immune cells  

  • Melbourne researchers have identified mechanisms leading to the functional deterioration of the immune system in response to severe viral infections, such as HIV or C19.
  • It is widely known that severe viral infections and cancer cause impairments to the immune system, including to T cells, a process called immune ‘exhaustion‘.
  • Overcoming immune exhaustion is a major goal for the development of new therapies for cancer or severe viral infections.
  • A team from the Peter Doherty Institute of Infection and Immunity (Doherty Institute) led by University of Melbourne’s Dr Daniel Utzschneider, Dr Sarah Gabriel and Professor Axel Kallies has focused on the question of when and how T cells lose their function and become ‘exhausted’.
  • It was previously thought that during severe infections, T cells lost their function slowly and over long periods of time.
  • This research published today in Nature Immunology, however, shows that T cells can be impaired within just a few days.
  • It also identifies several new mediators of immune exhaustion that maybe targeted in new therapies.
  • “This is an exciting finding, particularly in the context of C19 as one of the big questions is why some people get severely sick, while others experience mild disease,” Dr Utzschneider said.
  • “We looked at both mild and overwhelming Lymphocytic Choriomeningitis Virus infections in mice, which serves as a model for severe viral infections in humans, early after onset of disease, and identified striking differences at the molecular and functional level.”
  • Dr Gabriel explained: “In response to overwhelming infections that are difficult to eliminate and may become chronic, we were able to show that T cells down-regulate their function within days, while T cells responding to a weaker infection remained highly functional.”
  • T cells are at the heart of immunotherapy for cancer. Therefore, understanding how T cell function is impaired is central to improving these therapeutic approaches and applying them to other diseases, such as viral infections.
  • “These findings are extremely exciting. Our data show that T cells could be manipulated during early stages of severe viral infection to improve their activity,” Professor Kallies said.

Source: Severe viral infection overwhelms immune cells

7. Why C19 infection curves behave so unexpectedly  

  • With the first C19 epidemic peak behind them, many countries explained the decrease of infection numbers through non-pharmaceutical interventions. Phrases like “social distancing” and “flatten the curve” have become part of common vocabulary. 
  • Yet some explanations fell short: How could one explain the linear rise of infection curves, which many countries display after the first peak, in contrast to the S-shaped curves, expected from epidemiological models?
  • In a new paper published in PNAS (Proceedings of the National Academy of Sciences of the United States of America), scientists at the Complexity Science Hub Vienna (CSH) are the first ones to offer an explanation for the linear growth of the infection curve.
  • “At the beginning of the pandemic, C19 infection curves showed the expected exponential growth,” says Stefan Thurner, CSH president and professor for Science of Complex Systems at the Medical University of Vienna. This can be well explained by a so-called snowball effect: An infected person would infect a few others, and in a chain reaction, those would pass the virus on to a few others as well. 
  • “With measures like social distancing, governments tried to push the growth rate below the recovery rate and therefore massively reduce the number of new infections. In this logic, however, individuals would have infected less than one other person, and the curve would have flattened, eventually reaching zero – something that did not happen,” explains Thurner.
  • “What we saw instead was a constant level of infections with a similar number of new infections every day,” adds co-author Peter Klimek (CSH & Medical Univ of Vienna). “To explain this with standard epidemiological models would basically be impossible.”
  • The use of traditional epidemiological models would have required a lot of fine-tuning of parameters, making the model increasingly implausible. “If you want to balance measurements so that the effective reproduction number R stays exactly at 1 – something that would explain the linear growth -, you would have to reduce contacts by the same exact and constant percentage. In reality that is extremely unlikely,” says Klimek.
  • In fact, the probability to observe linear growth in these standard compartmental models is practically zero, the CSH scientists point out. They were therefore inspired to extend the model and look for further explanations.
  • The complexity scientists explained the linear shape of the curves through a different form of spreading than initially expected: They assumed that the spreading dynamic continued in small and limited clusters. “Most people went to work, got infected and spread it to two or three people at home, and then those people went to work or school again. The infection was basically spreading from cluster to cluster,” says Stefan Thurner. “The change of the infection curves from being S-shaped to a linear behavior is clearly a network effect – a dynamic very different from big superspreading events.”
  • The scientists showed that there is a critical number of contacts, which they call degree of contact networks or Dc, below which linear growth and low infection prevalence must occur. They found Dc to equal 7.2, assuming that people circulate in a coronavirus-relevant network of about five people, which is even lower during an effective lockdown (household-size 2.5 people on average).
  • Instead of having to fine-tune parameters, their model allows for a wide range of possibilities that keep the infection curves linear. It explains why linear infection curves appear in so many countries, irrespective of the magnitude of the imposed non-pharmaceutical interventions.
  • In a further step the scientists compared Austria, a country which responded with a severe lockdown early on, and the United States, which initially did not impose severe measures. According to Peter Klimek, their model works for both scenarios: “Both types of countries showed linear curves, but in the case of the US and other countries like Sweden, these just happened on a much higher level.”
  • The model not only explains the emergence of a linear growth regime, but also explains why the epidemic could halt below the levels of herd immunity by consequent social distancing. For the standard modelling procedure, the complexity scientists use a so-called compartmental model with SIR-models, extending it with the described cluster transmission.
  • But what will happen in the next months, with the potential of numbers rising again? With additional risk factors like people returning from vacation in other countries and more time spent inside, the spread of disease could change. “If infections rise again, there is the potential that linear curves turn to exponential growth again – something people described as a second wave,” Klimek concludes.

Source: Why COVID-19 infection curves behave so unexpectedly

D. Vaccines & Testing

1. 9 reasons to be optimistic that a C19 vaccine will be widely available in 2021  

  • As fall approaches rapidly, many are wondering if the race for a vaccine will bear fruit as early as January 2021.
  • I am a physician-scientist and infectious diseases specialist at the University of Virginia, where I care for patients and conduct research into C19. I am occasionally asked how I can be sure that researchers will develop a successful vaccine to prevent C19. After all, we still don’t have one for HIV, the virus that causes AIDS.
  • Here is where the current research stands, where I think we will be in five months, and why you can be optimistic about the delivery of a C19 vaccine.
1. HUMAN IMMUNE SYSTEM CURES C19
  • In as many as 99% of all C19 cases, the patient recovers from the infection, and the virus is cleared from the body.
  • Some of those who have had C19 may have low levels of virus in the body for up to three months after infection. But in most cases these individuals can no longer transmit the virus to other people 10 days after first becoming sick.
  • It should therefore be much easier to make a vaccine for the new coronavirus than for infections such as HIV where the immune system fails to cure it naturally. SARS-CoV-2 doesn’t mutate the way that HIV does, making it a much easier target for the immune system to subdue or for a vaccine to control.
2. ANTIBODIES TARGETING SPIKE PROTEIN PREVENT INFECTION
  • A vaccine will protect, in part, by inducing the production of antibodies against the spike protein on the surface of SARS-CoV-2, the virus that causes C19.
  • The virus needs the spike protein to attach to and enter human cells to reproduce. Researchers have shown that antibodies, like those made by the human immune system, bind to the spike protein, neutralize it, and prevent the coronavirus from infecting cells in laboratory culture.
  • Vaccines in clinical trials have been shown to raise anti-spike antibodies that block virus infection in cells in the lab.
  • At least seven companies have developed monoclonal antibodies, laboratory-manufactured antibodies that recognize the spike protein. These antibodies are entering clinical trials to test their ability to prevent infection in those who are exposed, for example, through a household contact.
  • Monoclonal antibodies may also be effective for treatment. During an infection, a dose of these monoclonal antibodies could neutralize virus, giving the immune system a chance to catch up and manufacture its own antibodies to combat the pathogen.
3. SPIKE GLYCOPROTEIN CONTAINS MULTIPLE TARGETS
  • The spike protein has many locations where antibodies can bind to and neutralize the virus. That’s good news because with so many vulnerable spots, it will be difficult for the virus to mutate to avoid a vaccine.
  • Multiple parts of the spike would need to mutate to evade neutralizing anti-spike antibodies. Too many mutations to the spike protein would change its structure and render it incapable of binding to ACE2, which is key to infecting human cells.
4. WE KNOW HOW TO MAKE A SAFE VACCINE
  • Safety of a new C19 vaccine is improved by researchers’ understanding of potential vaccine side effects and how to avoid them.
  • One side effect seen in the past was antibody-dependent enhancement of infection. This occurs when antibodies don’t neutralize the virus but instead allow it to enter into cells via a receptor intended for antibodies. Researchers have found that by immunizing with the spike protein, high levels of neutralizing antibodies can be produced. This lessens the risk of enhancement.
  • A second potential problem posed by some vaccines is an allergic reaction that causes inflammation in the lung, as was seen in individuals who received a respiratory syncytial virus vaccine in the 1960s. This is dangerous because inflammation in the lung air spaces can make it difficult to breathe. However, researchers have now learned how to design vaccines to avoid this allergic response.
5. SEVERAL DIFFERENT VACCINES IN DEVELOPMENT
  • The U.S. government is supporting the development of several different vaccines via Operation Warp Speed.
  • The goal of Operation Warp Speed is to deliver 300 million doses of a safe and effective vaccine by January 2021.
  • The U.S. government is making a major investment, committing US$8 billion to seven different C19 vaccines.
  • By supporting multiple C19 vaccines, the government is hedging its bets. Only one of these vaccines needs to prove safe and effective in clinical trials for a C19 vaccine to be made available to Americans in 2021.
6. VACCINES PASSING THROUGH PHASE I AND II TRIALS
  • Phase I and phase II trials test if a vaccine is safe and induces an immune response. Already the results to date from three different vaccine trials are promising, triggering the production of anti-spike neutralizing antibodies levels that are two- to four-fold higher than those seen in people who have recovered from C19.
  • Moderna, Oxford, and Chinese company CanSino have all demonstrated the safety of their vaccines in phase I and phase II trials.
7. PHASE III CLINICAL TRIALS ARE UNDERWAY
  • During a phase III trial, the final step in vaccine development process, the vaccine is tested on tens of thousands of individuals to determine if it works to prevent infection with SARS-CoV-2, and that it is safe.
  • The vaccine produced by Moderna and NIH and the vaccine from Oxford-AstraZeneca began phase III trials in July. Other C19 vaccines will be starting phase III within weeks.
8. ACCELERATING VACCINE PRODUCTION AND DEPLOYMENT
  • Operation Warp Speed is paying for the production of millions of doses of vaccines and supporting vaccine manufacturing at an industrial scale even before researchers have demonstrated vaccine efficacy and safety.
  • The advantage of this strategy is that once a vaccine is proven safe in phase III trials, a stockpile of it will already exist and it can be distributed immediately without compromising full assessment of safety and efficacy.
  • This is a more prudent approach than that of Russia, which is vaccinating the public with a vaccine before it has been shown to be safe and effective in phase III.
9. VACCINE DISTRIBUTORS ARE BEING CONTRACTED NOW
  • McKesson Corp., the largest vaccine distributor in the U.S., has already been contracted by the CDC to distribute a C19 vaccine to sites—including clinics and hospitals—where the vaccine will be administered.
  • I believe that it is realistic that we will know sometime in late 2020 whether some C19 vaccines are safe, exactly how effective they are, and which ones should be used to vaccinate the U.S. population in 2021.

Source: 9 reasons to be optimistic that a COVID-19 vaccine will be widely available in 2021

2. A Vaccine That Stops C19 Won’t Be Enough  

Opinion by Adam Finn and Richard Malley

  • Not long after the new coronavirus first surfaced last December, an ambitious prediction was made: A vaccine would be available within 12 to 18 months, and it would stop the pandemic.
  • Despite serious challenges — how to mass manufacture, supply and deliver a vaccine worldwide — the first prong of that wish could well be fulfilled. Eight vaccine candidates are undergoing large-scale efficacy tests, so-called Phase 3 trials, and results are expected by the end of this year or early 2021.
  • But even if one, or more, of those efforts succeeds, a vaccine might not end the pandemic. This is partly because we seem to be focused at the moment on developing the kind of vaccine that may well prevent C19, the disease, but that wouldn’t do enough to stop the transmission of SARS-CoV-2, the virus that causes C19.
  • Doctors usually explain vaccines to patients and the parents of young children by describing how those protect us from a particular disease: An attenuated form of a pathogen, or just a bit of it, is inoculated into the human body in order to trigger its immune response; having learned to fight off that pathogen once, the body will remember how to fend off the disease should it be exposed to the same pathogen later.
  • A vaccine’s ability to forestall a disease is also how vaccine developers typically design — and how regulators typically evaluate — Phase 3 clinical trials for vaccine candidates.
  • Yet the best vaccines also serve another, critical, function: They block a pathogen’s transmission from one person to another. And this result, often called an “indirect” effect of vaccination, is no less important than the direct effect of preventing the disease caused by that pathogen. In fact, during a pandemic, it probably is even more important.
  • That’s what we should be focusing on right now. And yet we are not.
  • Stopping a virus’s transmission reduces the entire population’s overall exposure to the virus. It protects people who may be too frail to respond to a vaccine, who do not have access to the vaccine, who refuse to be immunized and whose immune response might wane over time.
  • The benefits of this approach have been demonstrated with other pathogens and other diseases.
  • The Haemophilus influenzae type B (Hib) conjugate vaccines were designed, and licensed in the early 1990s, to prevent young children from developing serious infections such as meningitis. Soon enough an unexpected and welcome side benefit became clear: The vaccine interrupted the bacterium’s transmission; after its introduction, occurrences of the disease dropped also in groups that had not been vaccinated.
  • The human papillomavirus (HPV) vaccines were developed to prevent cervical cancer and genital warts in women. They have proved immensely effective among the women to whom they are administered — and up to 50 percent effective at preventing genital warts among unvaccinated men, according to a 2017 study of the health insurance records for 2005-10 of some nine million people in Germany.
  • To understand why this is the case, remember what it takes for you to become ill from a pathogen, be it a virus or a bacterium.
  • First, you are exposed to it. Then it infects you. While you are infected, you may infect others. In some cases, the infection develops into a disease. In other cases, it doesn’t: Though infected, you remain asymptomatic.
  • One way that vaccines can interrupt a pathogen’s transmission cycle is by preventing the pathogen from causing an infection in the first place. This is how many common vaccines — against measles, mumps, rubella and chickenpox — operate.
  • Other vaccines — like the ones against meningococcal meningitis or pneumonia brought on by the pneumococcus bacterium — can block the transmission of the pathogen by interfering with the infection or by decreasing either the quantity of pathogen that the infected patient sheds or the duration of the shedding period.
  • Some recipients of the pneumococcal pneumonia vaccine simply don’t get infected with the bacterium; others do get infected and carry the bacterium in their nose, but in smaller amounts and for shorter periods of time than if they had not been vaccinated.
  • Much still needs to be learned about precisely how such mechanisms work — what part do antibodies play? T cells? — but the upshot from these examples is this: Vaccines can block the transmission of viruses or bacteria, and they can do so in several ways.
  • Given the communitywide benefits of accomplishing that, especially in a pandemic, current vaccine-development efforts should prioritize finding vaccines that limit the transmission of SARS-CoV-2.
  • The U.S. Food and Drug Administration has stated that preventing a SARS-CoV-2 infection is in itself a sufficient endpoint for the Phase 3 trials of vaccine candidates — that it is an acceptable alternative goal to preventing the development of C19. The World Health Organization has said that “shedding/transmission” is as well.
  • These guidelines are an important signal, especially considering that the F.D.A. has never approved a vaccine based on its effects on infection alone; instead, the agency has focused exclusively on the vaccine’s effectiveness at disease prevention.
  • And yet vaccine developers do not seem to be heeding this new call.
  • Based on our review of the Phase 3 tests listed at ClinicalTrials.gov, a database of trials conducted around the world, the primary goal in each of these studies is to reduce the occurrence of C19.
  • Four of the six C19 vaccine trials for which information is available say they will also evaluate the incidence of SARS-CoV-2 infections among subjects — but only as an ancillary outcome.
  • This approach is shortsighted: One cannot assume that a vaccine that prevents the development of C19 in a patient will necessarily also limit the risk that the patient will transmit SARS-CoV-2 to other people.
  • For example, a study of young Australian teenagers published in the New England Journal of Medicine early this year found that the vaccine used to prevent the diseases caused by the B strain of meningococcus in children and teenagers “had no discernible effect” on the presence of the relevant bacterium in the throats of vaccinated subjects displaying no symptoms.
  • The inactivated polio vaccine prevalent in many developed countries today, known as IPV, is highly effective at protecting individuals against polio. But it is far less effective at reducing viral shedding, at least in fecal excretions, than the oral vaccine, known as OPV, used more widely in other parts of the world.
  • In the late 1990s, the United States, like other wealthy countries, replaced with an acellular vaccine the killed-whole-cell pertussis vaccine it had previously used against whooping cough. A resurgence of whooping cough already was underway, but it accelerated then: Although the new vaccine was better than the previous one at protecting the inoculated from the disease, it was less good at blocking transmission of the bacterium that causes the cough.
  • Conversely, a vaccine that, let’s say, offers older adults only modest protection against developing a disease might nonetheless be very effective, when administered to healthy adults or children, at curbing a pathogen’s transmission in a population overall.
  • This is the case with the pneumococcal conjugate vaccine. A 2015 study published in the New England Journal of Medicine found that the vaccine reduced the occurrence of pneumonia in inoculated adults age 65 or older by only about 45 percent. Yet, according to a study last year by researchers at the Centers for Disease Control and Prevention and Stanford University, the immunization of infants and toddlers reduced ninefold the incidence of pneumococcal disease in the elderly.
  • With some vaccines, for some diseases, the indirect benefits of vaccination can be greater than the direct effects.
  • Based on these precedents, it could be a grave mistake for vaccine developers now to hew only, or too closely, to the single-minded goal of preventing C19, the disease.
  • Doing so could mean privileging vaccines that don’t block the transmission of SARS-CoV-2 at all, or abandoning vaccines that block transmission well enough but that, by prevailing standards, are deemed to not forestall enough the development of C19.
  • That, in turn, would essentially mean that the only way to ever get rid of SARS-CoV-2 would be near-universal immunization — a herculean task.
  • Focusing on how to block the coronavirus’s transmission is a much more efficient approach.
  • This is why randomized controlled trials of the vaccines currently under consideration should include regular monitoring for the presence of SARS-CoV-2 in study subjects. The goal should be to evaluate whether the subjects acquire the infection at all, and for how long, as well as how abundantly they shed and spread the virus, when and how.
  • Studying these issues could also help cast a light on the role of so-called superspreading events in this pandemic.
  • More and more research suggests that a very small number of instances — gatherings at restaurants or bars, choir rehearsal, funerals, church services — might account for a vast majority of the cases of infection overall.
  • But the discussion about those instances has tended to focus on their settings and circumstances, such as the presence of crowds in confined spaces for extended periods of time.
  • Yet the question of whether some infected individuals, perhaps especially at certain stages of infection, are particularly infectious — whether they, themselves, are superspreaders — also needs to be studied head-on: When does contagiousness peak in whom and why? And can vaccines modify any of that?
  • The best vaccines don’t just protect the inoculated from getting sick from a disease. They also protect everyone else from even contracting the pathogen that causes that disease.
  • Preventing the very transmission of SARS-CoV-2, no less than stopping it from turning into C19, should be a main priority of current efforts to develop the vaccines to end this pandemic.

Source: Opinion | Are We Looking for the Wrong Coronavirus Vaccines?

3. New Low-Cost, Accurate C19 Antibody Detection Platform Developed 

Portable imager could massively increase testing across nation by end of 2020
  • A robust, low-cost imaging platform utilizing lab-on-a-chip technology created by University of California, Irvine scientists may be available for rapid coronavirus diagnostic and antibody testing throughout the nation by the end of the year.
  • The UCI system can go a long way toward the deployment of a vaccine for C19 and toward reopening the economy, as both require widespread testing for the virus and its antibodies. So far, antibody testing in the U.S. has been too inaccurate or expensive to reach the necessary numbers.
  • But UCI investigators Weian Zhao, Per Niklas Hedde, Enrico Gratton and Philip Felgner believe that their new technology can help accelerate the testing process quickly and affordably. Their discovery appears in the journal Lab on a Chip, which is published by the Royal Society of Chemistry.
  • “We need to test millions of people a day, and we’re very far from that,” said Hedde, a project scientist in pharmaceutical sciences and the study’s lead author. “This accurate testing platform enables public health officers to implement individualized mitigation strategies that are needed to safely reopen the country and economy.”
How it works
  • Using blood from a finger prick, the UCI test probes hundreds of antibody responses to 14 respiratory viruses, including coronavirus, in a mere two to four hours. Identifying responses to viral infections with symptoms similar to those of C19 will keep hospitals clear of patients with standard colds and flus.
  • The results are printed on a low-cost imaging platform. The TinyArray imager combines a 3D-printed prototype with an off-the-shelf LED and a small 5-megapixel camera to find markers for many antibodies simultaneously. This ensures accuracy equal to that of expensive imaging systems but makes the platform portable enough to deploy anywhere – at a cost of only $200.
  • The same device can also process the results of commonly used nose swab tests for coronavirus so that patients can be tested for C19 and its antibodies on a single platform.
  • Currently, most antibody tests only check for one or two antigens, the foreign substances that cause the body to produce antibodies.
  • “A month or two ago, testing was kind of regarded as the Wild West,” said Zhao, a professor of pharmaceutical sciences, adding that most coronavirus antibody tests are “just not accurate.”
  • Systems that test for the full range of antibodies necessary for reliable results require imaging machines that cost $10,000 to $100,000 and are too bulky for widespread use. Areas without the resources to acquire one of these machines have to send their samples to external labs for testing, meaning that results take days instead of hours.
Big impact
  • Large-scale testing will determine what percentage of the population had C19 but never showed symptoms, which will have a big impact on public health and reopening decisions.
  • “What if it turns out that a larger percentage of the people in a community have already contracted the virus?” Zhao said. “This means you are closer to accomplishing herd immunity.”
  • And understanding what antibodies are produced and how long they last will be key in developing an effective vaccine and administering the right dosage. This may be critical for years to come if the virus mutates, requiring updates much like yearly flu vaccinations.
  • The UCI team has already completed 5,000 tests in Orange County, and the final goal is to test 20,000 samples per unit a day. The researchers are partnering with UCI startups Velox Biosystems Inc. and Nanommune Inc. to scale up production. They expect that the TinyArray imager will be ready to deploy across the U.S. by the end of 2020 and are working with scientists in Uruguay, Russia and Thailand to develop similar systems for their nations.
  • “This would be great for a low-income country,” Hedde said. “Because the device’s materials are cheap and easy to obtain, the platform is easy to manufacture and use in low-resource areas, making testing accessible on a world scale.”

Source: New Low-Cost, Accurate COVID-19 Antibody Detection Platform Developed

4. Do-it-yourself coronavirus testing sparks kudos, and caution  

  • Leading public health experts, frustrated with chronic delays in coronavirus testing, are on a mission to persuade federal regulators to authorize cheap, at-home tests that would deliver results in minutes and could help the country turn the corner on the pandemic.
  • The campaign comes as the FDA recently adopted guidelines aimed at ensuring accurate results for do-it-yourself C19 tests. While several companies have developed home test kits and are pushing to get them on the market, these scientists say the new thresholds are so strict that few home test kits will be able to meet them.
  • In pressing the FDA, these scientists argue that fast, frequent coronavirus tests, taken daily or several times a week, can be crucial to reopening schools and businesses — and keeping them open. The tests, they say, would catch silent carriers who do not show symptoms but can potentially spread the virus widely.
  • The concept behind a home kit is simple and is similar to how doctors quickly detect strep throat and the flu: A paper strip could test a saliva or a nasal sample taken by swab and return a positive or negative result inside of 15 minutes. Parents could swab their children and find out if they are infectious before deciding whether to send them off to school. College students, workers, and anyone heading to a restaurant or gathering could benefit from such tests, as well.
  • “These have so much promise because they can help squelch the infections altogether,” said Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T. H. Chan School of Public Health. “If we can all get the number of our cases very low, everyone is safer.”
  • But without these new options, Mina and other scientists said, the country will remain hamstrung by the current system that relies on tests sent to a lab for processing. Critics say that system was never designed to handle the massive load of coronavirus tests that has led to delays of more than a week in getting results.
  • Mina has joined several public health experts in promoting at-home screening, known as antigen tests, on social media, and chiding regulators for their new rules.
  • On Friday, a frustrated Mina disclosed that he’s been talking with companies about the possibility of not waiting any longer for FDA approval and “just producing hundreds of thousands or millions” of these tests, with the caveat that they only be used for large-scale studies.
  • “I am talking to governors and senators and congressmen, and they’re writing letters to the FDA, so this is moving,” Mina said. “There is a lot of pressure from all walks of life right now, trying to get these things approved and to get the FDA to budge on this.”
  • But the FDA has so far steered clear of the debate.
  • The system in wide use now, known as molecular tests, requires a multistep laboratory process to extract genetic material from a nasal or saliva sample, amplify it, and search for signs of the coronavirus. By contrast, rapid antigen tests simply detect specific proteins on the surface of the virus, a process that doesn’t require time-consuming laboratory equipment. But they can miss infections and produce more false negative findings, especially among people who do not have heavy loads of the virus.
  • Moreover, scientists are finding that people with C19 are generally most infectious the first week or so after being exposed to coronavirus and often before they show symptoms. But patients often face waiting times to get tested, and while molecular tests can still detect traces of virus and return a positive finding, the result may come well past the time many people are infectious.
  • To guard against false negative results with rapid antigen tests, and to catch people when they are most infectious, consumers would be expected to test themselves frequently, perhaps several times a week, Mina and other scientists say. The cost of each test is expected to be a few dollars, versus the $100-plus out-of-pocket fee often charged for molecular tests not covered by insurance.
  • “I am pushing the instant coffee model vs. the espresso machine model,” Mina said.
  • An FDA spokeswoman declined to comment on the debate over at-home C19 rapid antigen tests, instead noting the agency’s statement when it released new guidelines on July 29. The guidelines require over-the-counter antigen tests for C19 to have the ability, known as test sensitivity, to detect at least 90 percent of cases. That’s 20 to 30 percentage points more sensitive than most C19 rapid home tests now in development. By contrast, the FDA requires C19 tests processed in labs to detect at least 95 percent of cases.
  • “While the recommended sensitivity for these non-lab tests is lower than lab-based tests, the tremendous benefits of broader access to simple and fast testing options generally outweighs this risk,” the FDA said in its July statement.
  • The Rockefeller Foundation, a nonprofit focused on health, energy, and social justice issues, recently joined the call for the federal government to work more closely with companies and scientists to develop affordable rapid coronavirus antigen tests. It has committed $100 million to a C19 testing and contact tracing initiative.
  • “We need a paradigm shift from exquisitely accurate but slow tests, to fast and good enough to quarantine,” said Mara G. Aspinall, an Arizona State University professor, and coauthor of the foundation’s coronavirus plan, in a statement. “Slow and accurate works for clinical management, but this virus is a sprinter not a marathoner. We need fast and frequent tests just to keep up.”
  • But other health specialists say too many details have yet to be worked out to open the gates on do-it-yourself C19 testing. Dr. Kimberle Chapin, a pathology and laboratory medicine professor at Brown University’s Warren Alpert School of Medicine, said she is concerned the home tests will not be affordable for everyone. And, she said, it’s not clear how test results from home screening would be reported to physicians and local and state health officials.
  • She said physicians need to be in the loop to explain to consumers about quarantining, while health officials need to know when and where people are testing positive to catch clusters and outbreaks before they spread.
  • “Increasing the availability of COVID tests and options for testing needs to be done within a larger public health strategy that includes follow-up care, contact tracing, and data reporting,” said Chapin, who also is microbiology director at Lifespan Academic Medical Center in Rhode Island.
  • Karla Satchell, professor of microbiology-immunology at Northwestern University Feinberg School of Medicine, said antigen tests will play a pivotal role but must be more accurate than most currently in development.
  • “Even at 90 percent [sensitivity] that means 10 percent of the positives are walking through your front door to work and that could be a high number of people,” Satchell said. “We need to keep high standards for what we bring to market.”
  • One company that says it has a rapid antigen test ready to go is E25Bio, a Cambridge startup spun from a lab at the Massachusetts Institute of Technology. Company cofounder Irene Bosch said E25Bio developed the test in March but couldn’t persuade any local hospitals to validate it by testing several hundred patients and comparing the results to those from molecular tests. The company finally got the go-ahead from a hospital in Florida this summer, she said.
  • The test, Bosch said, can detect about 70 percent of cases among patients with high amounts of coronavirus, and becomes less sensitive with decreasing viral levels. E25Bio has submitted an application to the FDA, but isn’t optimistic, given the agency’s guidelines for a 90 percent threshold.
  • “What would make the FDA change its mind?” Bosch asked in frustration.
  • Other countries, including Belgium, have approved rapid antigen tests for C19, with sensitivity rates lower than 60 percent, Bosch said.
  • “It is better to see with one eye,” she said, “than to be blind.”

Source: Do-it-yourself coronavirus testing sparks kudos, and caution

5. To Test Spread of C19, Scientists Put on a Concert  

  • The German pop singer Tim Bendzko was trying his best to energize the crowd at Quarterback Immobilien Arena here on Saturday morning. Flanked by band members and backup singers, he bounced across a stage at the indoor concert and sports venue, thrusting his microphone toward about 1,400 tightly packed audience members, prompting them to sing along.
  • The response was a muffled hum — unsurprising, given that the audience members were wearing masks and sitting in sweltering heat. Still, an undaunted Mr. Bendzko thanked them and said, “On this day, you are saviors of the world.”
The experiment included about 1,400 volunteers in the audience.
  • The experiment included about 1,400 volunteers in the audience.
  • They were not typical concertgoers, but volunteers in an elaborate study by a team at Martin Luther University Halle-Wittenberg called Restart 19. Each attendee, outfitted with a digital location tracker and hand disinfectant laced with fluorescent dye, were carefully positioned on seats as part of one of the first experiments by scientists to track the risks of coronavirus infection posed by large, indoor events.
  • Researchers hope to use their results to determine which elements of events like this pose the greatest risk for transmission and help create guidelines for limiting such dangers and safely restarting live performances around the world.
  • The live-music and events sector has been among the hardest hit by the coronavirus pandemic. In Germany alone, it brings in 130 billion euros in revenue each year, according to a recent study commissioned by the I.G.V.W., an industry group there. Concert venues were among the first to shut down to slow the virus’s spread, and their futures remain uncertain.
The audience was tested in various configurations of social distancing and other safety measures.
  • The audience was tested in various configurations of social distancing and other safety measures.
  • Indoor performances have returned in Germany, but slowly, under rules that vary from state to state. Many venue operators and event organizers, however, argue that the limitations on crowd size and hygiene requirements imposed by authorities make it economically unviable for venues that aren’t subsidized by the state to restart operations. In the United States, health experts have said that arena concerts would likely not happen on a wide scale until a vaccine becomes available.
  • Leipzig is in the state of Saxony, where indoor events are allowed with up to 1,000 attendees — amid strict hygiene and distancing rules. But Philipp Franke, a manager of the arena hosting the study, said in a phone interview that this number was still too low for him to reopen. The attendance limit is scheduled to be raised in September, but Germany’s rising infection numbers have drawn increased scrutiny to the plan.
  • Mr. Franke hoped that the study’s results from would allow politicians to make informed decisions about resuming concerts and indoor sports. “Cultural events are socially important,” he added. “A society needs such events in order to find some fulfillment and an outlet.”
  • The study is being led by Dr. Stefan Moritz, the head of the clinical infectious diseases department at the university. In a phone interview, he said the experiment was a response to the fact there was not enough scientific literature available for policymakers about the dangers of events like the one on Saturday.
  • “We know the personal contacts at the concert are risky, but we don’t know where they happen,” he said. “Is it at the entrance? Is it at the bleachers?”
  • Dr. Moritz concluded that the best way to bring in reliable data would be to stage an actual concert. The arena in Leipzig agreed to help manage the logistics and recruited Mr. Bendzko. In an interview backstage on Saturday, he said he took part in the study because “it is better to do something active to move things along than to sit at home and wallow in insecurity.”
  • He had played some small concerts in recent months at drive-in theaters, he said, but they were not economically viable. “Applause doesn’t pay our rent,” he added.
Attendees were asked to visit concessions and restrooms during breaks.
  • Attendees were asked to visit concessions and restrooms during breaks.
  • To minimize the risk of infection, all volunteers were tested for the coronavirus in advance, and had their temperatures checked upon arrival. Outfitted with their tracking devices, masks and fluorescent disinfectant, they were then asked to simulate different concert scenarios over the course of 10 hours: one with no social distancing, another with moderate safety measures and a third with strict ones.
  • Each iteration included performances by Mr. Bendzko and a break, during which participants simulated trips to vendors for food and drinks and made bathroom visits. Using trackers, the staff monitored the number of times attendees came close to one another, and later used ultraviolet lamps to determine which surfaces were covered with the most fluorescent disinfectant by the end of the day.
  • Dr. Moritz said that the most intriguing finding likely would be related to aerosol spread. Scientists have recently confirmed that the virus can remain suspended in the air, possibly for hours in closed environments.
  • “It’s so weird what happens with these movements of air,” he said. “Things you wouldn’t expect.”
The scientists used a smoke machine to study the spread of aerosols.
  • The scientists used a smoke machine to study the spread of aerosols.
  • To simulate the spread of aerosols in the arena on Saturday, staff used a smoke machine to emit a cloud of fog into the rafters. It drifted upward before moving into a spiral shape and spreading toward the audience. The spread of particles in the space was modeled by Mr. Moritz’s team, who will compared it with data collected by carbon dioxide sensors during the study.
  • Dr. Moritz said that results from the study, which was sponsored by the states of Saxony and Saxony-Anhalt, were expected be ready in early October, and argued that the findings likely could be applied to similar events and venues around the world. He added that he had already been contacted by researchers in Australia, Belgium and Denmark who planned to carry out similar studies.
  • For many people in the audience, volunteering was worth it for the experience of finally going to a concert after months of deprivation.
  • For volunteers, the experiment was an opportunity to hear live music for the first time in several months.
  • Bianca Tenten, a 21-year-old student from Cologne, Germany, said that listening to music at home couldn’t replicate the sense of togetherness and the spontaneous encounters that she often experienced at live music events. She added that for concert organizers and artists, “there is a passion and a love there.”
  • And Stefanie Oehme, a 34-year-old teacher who traveled to Leipzig from Dresden, said that she had grown dispirited with people who have claimed that limitations on public life were here to stay.
  • “I think this is a sign of things moving back toward the old normal,” she said. “It makes it a bit more tangible.”

Source: To Test the Dangers of Live Music, These Scientists Put on a Concert 

E. Improved & Potential Treatments

1. Roche to partner with Regeneron on C19 treatment 

  • Roche Pharmaceuticals is teaming up with Regeneron to develop and distribute Regeneron’s C19 investigational antiviral antibody combination.
  • The treatment, known as REGN-COV2, is being developed as a treatment option for people already experiencing symptoms of C19. It also has the potential to prevent infection in people exposed to the virus, thus slowing the spread of the global pandemic.
  • Through this collaboration, the companies are expected to increase the supply of REGN-COV2 to at least three and a half times the current capacity — with the potential for even further expansion.
  • REGN-COV2 is currently involved in two Phase 2/3 clinical trials for the treatment of C19 and in a Phase 3 trial for the prevention of C19. If approvals are granted, Regeneron will distribute and record sales for REGN-COV2 in the U.S. while Roche will be responsible for distribution outside the U.S.
  • “We are excited about the potential for one medicine to serve both as a treatment for those infected as well as protection for people exposed to the virus. REGN-COV2 could be a critical line of defense against the C19 pandemic,” Bill Anderson, CEO of Roche Pharmaceuticals, said. “We’re committing our manufacturing expertise and capacity, and our global distribution network to bring Regeneron’s potential antibody combination to as many people around the world as we possibly can.”
  • Under the terms of the agreement, each company has committed to dedicating a certain manufacturing capacity to REGN-COV2 each year. Further, each company will bear its own distribution expenses in their designated territories. The collaborators will jointly fund and execute the ongoing Phase 3 prevention and Phase 1 healthy volunteer safety studies as well as additional global studies. Roche will be primarily responsible for securing regulatory approvals outside the United States.
  • “Regeneron has progressed the REGN-COV2 research and development program at record speed and worked tirelessly to maximize our in-house manufacturing capacity,” Leonard S. Schleifer, president and CEO of Regeneron, said. “This major collaboration with Roche provides important scale and global expertise to bring REGN-COV2 to many more patients in the United States and around the globe.”
  • REGN-COV2 was designed to block infectivity of the coronavirus. Its development, manufacturing, and clinical trials have been funded in part by the Biomedical Advanced Research and Development Authority (BARDA).

Source: Roche to partner with Regeneron on COVID-19 treatment 

2. Hepatitis Drugs May Be Effective C19 Treatment  

  • Three articles all researched the use of sofosbuvir and daclatasvir for the treatment of C19. These three papers come from Iran, which has developed its own pill containing sofosbuvir and daclatasvir, and is in a position to test this in a large clinical trial as Iran is a massively impacted country, reporting some 2500 cases and 200 deaths a day.
  • Currently no effective antiviral therapy has been found to treat C19. The aim of the trials was to assess if the addition of sofosbuvir and daclatasvir, a drug combination commonly used for the treatment of hepatitis C, improved clinical outcomes in patients with moderate or severe C19.
  • In one trial, researchers recruited 66 patients and allocated them to either the treatment group or the control group. Clinical recovery within 14 days was achieved by 88% in the treatment group and 67% in the control group. The treatment group had a significantly shorter median duration of hospitalization (6 days) than the control group (8 days). Cumulative incidence of hospital discharge was significantly higher in the treatment group versus control. Three patients died in the treatment group and five in the control group. No serious adverse events were reported.
  • In another study, subjects suffering from C19 were divided into two groups with one group receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine.
  • The results indicated that median duration of stay was five days for the sofosbuvir/daclatasvir group and nine days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 6% and 33% for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17%.
  • The results of these studies suggest that the addition of sofosbuvir and daclatasvir to standard care may reduce the duration of hospital stays for C19 patients compared to standard care alone.
  • “Despite the encouraging initial results, it is too early to reach a verdict. Larger, well-designed studies are required to confirm our results,” said Shahin Merat, the lead author of one of the Journal of Antimicrobial Chemotherapy articles. “A network of five randomized clinical trials has been set up, to test sofosbuvir plus daclatasvir in over 2000 patients with C19, in Iran, Brazil, Egypt, and South Africa. By October, we should know if this treatment could be approved for worldwide use.”

Source: Hepatitis Drugs May Be Effective COVID-19 Coronavirus Treatment

F. Concerns & Unknowns

1. C19 Medical Mystery: Patients Come Off Ventilator But Linger In Coma  

  • Leslie Cutitta said yes, twice, when clinicians from Massachusetts General Hospital in Boston called asking whether she wanted them to take — and then continue — extreme measures to keep her husband, Frank Cutitta, alive.
  • The first conversation, in late March, was about whether to let Frank go or to try some experimental drugs and treatments. The second call was just a few days later. Hospital visits were banned, so Leslie Cutitta couldn’t be with her husband or discuss his wishes with the medical team in person. So she used stories to try to describe Frank’s zest for life.
  • “Frank used to joke that he wanted to be frozen, like Ted Williams, until they could figure out what was wrong with him if he died,” says Leslie Cutitta. It wasn’t a serious end-of-life discussion, but Cutitta knew her husband would want every possible life-saving measure.
  • So the Cutittas hung on and a small army of ICU caregivers kept working. On April 21, after 27 days on a ventilator, Frank’s lungs had recovered enough to remove the breathing tube.
  • After the removal, it typically takes hours, maybe a day, for the patient to return to consciousness. The body needs that time to clear the drugs that keep the patient sedated and comfortable — able to tolerate intubation and mechanical ventilation. But doctors across the U.S. and in other countries have noted a troubling phenomenon associated with some C19 cases: Even after extubation, some patients remain unconscious for days, weeks or longer. There’s no official term for the problem, but it’s being called a “prolonged” or “persistent” coma or unresponsiveness.
  • Frank Cutitta, 68, was one of those patients. He just didn’t wake up.
  • “It was a long, difficult period of not — just not knowing whether he was going to come back to the Frank we knew and loved,” says Leslie Cutitta. “It was very, very tough.”
  • Doctors who are studying the phenomenon of prolonged unresponsiveness are concerned that medical teams are not waiting long enough for these C19 patients to wake up, especially when ICU beds are in high demand during the pandemic.
  • As Frank’s unresponsive condition continued, it prompted a new conversation between the medical team and his wife about whether to continue life support. Although he no longer needed the ventilator, he still required a feeding tube, intravenous fluids, catheters for bodily waste and some oxygen support.
  • Leslie Cutitta recalls a doctor asking her: “If it looks like Frank’s not going to return mentally, and he’s going to be hooked up to a dialysis machine for the rest of his life in a long-term care facility, is that something that you and he could live with?”
  • Leslie Cutitta struggled to imagine the restricted life Frank might face. Every day, sometimes several times a day, she would ask Frank’s doctors for more information: What’s going on inside his brain? Why is this happening? When might something change?
  • Their candid and consistent answer was: We don’t know.
  • “Because this disease is so new and because there are so many unanswered questions about C19, we currently do not have reliable tools to predict how long it will take any individual patient to recover consciousness,” says Dr. Brian Edlow, a critical care neurologist at Mass General.
  • Given all the unknowns, doctors at the hospital have had a hard time advising families when a patient has remained unresponsive for weeks, post-ventilator. Some families in that situation have decided to remove other life supports so the patient can die. Edlow can’t say how many.
  • “It is very difficult for us to determine whether any given patient’s future will bring a quality of life that would be acceptable to them,” Edlow says, “based on what they’ve told their families or written in a prior directive.”
  • There are lots of theories about why C19 patients may take longer to regain consciousness than other ventilated patients, if they wake up at all. C19 patients appear to need larger doses of sedatives while on a ventilator, and they’re often intubated for longer periods of time than is typical for other diseases that cause pneumonia. Low oxygen levels, due to the virus’s effect on lungs, may damage the brain. Some of these patients have inflammation related to C19 that may disrupt signals in the brain, and some experience blood clots that have caused strokes.
  • “So there are many potential contributing factors,” Edlow says. “The degree to which each of those factors is playing a role in any given patient is still something we’re trying to understand.”
  • One of the first questions researchers hope to answer is how many C19 patients end up in this prolonged, sleeplike condition after coming off the ventilator.
  • “In our experience, approximately every fifth patient that was hospitalized was admitted to the ICU and had some degree of disorders of consciousness,” says Dr. Jan Claassen, the director of neurocritical care at New York’s Columbia University Medical Center. “But how many of those actually took a long time to wake up, we don’t have numbers on that yet.”
  • An international research group based at the University of Pittsburgh Medical Center expects to have in September some initial numbers on C19 brain impacts, including the problem of persistent comas. Some C19 patients who do eventually regain consciousness still have cognitive difficulties.
  • To try to get a handle on this problem at Columbia, Claassen and colleagues created a “coma board,” a group of specialists that meets weekly. Claassen published a study in 2019 that found that 15% of unresponsive patients showed brain activity in response to verbal commands. A case reported by Edlow in July described a patient who moved between a coma and minimal consciousness for several weeks and was eventually able to follow verbal commands.
  • This spring, as Edlow observed dozens of Mass General C19 patients linger in this unresponsive state, he joined Claassen and other colleagues from Cornell’s Weill Medical College to form a research consortium. The researchers are sharing their data to determine the cause of prolonged coma in C19 patients, find treatments and better predict which patients might eventually recover, given enough time and treatment.
  • The global research effort has grown to include more than 222 sites in 45 countries. Prolonged or persistent comas are just one area of research, but one that is getting a lot of attention.
  • Dr. Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, is leading the international effort.
  • Chou says families want to know “whether a patient can wake up and be themselves.” Answering that question “depends on how accurate we are at predicting the future, and we know we’re not very accurate right now.”
  • A CT scan of Frank Cutitta’s brain showed some residue from blood clots but was otherwise “clean.”
  • “From what they could tell, there was no brain damage,” Leslie Cutitta says.
  • And then on May 4, after two weeks with no signs that Frank would wake up, he blinked. Leslie and her two daughters watched on FaceTime, making requests such as “Smile, Daddy” and “Hold your thumb up!”
  • “At least we knew he was in there somewhere,” she says.
  • It was another week before Frank could speak and the Cutittas got to hear his voice.
  • “We’d all be pressing the phone to our ears, trying to catch every word,” Leslie Cutitta recalls. “He didn’t have a lot of them at that point, but it was just amazing, absolutely amazing.”
  • Frank Cutitta spent a month at Spaulding Rehabilitation Hospital. He’s back home now, in a Boston suburb, doing physical therapy to strengthen his arms and legs. He says he slurs words occasionally but has no other cognitive problems.
  • Many hospitals use 72 hours, or three days, as the period for patients with a traumatic brain injury to regain consciousness before advising an end to life support. As C19 patients fill ICUs across the country, it’s not clear how long hospital staff will wait beyond that point for those patients who do not wake up after a ventilator tube is removed.
  • Joseph Giacino directs neuropsychology at Spaulding and says he’s worried hospitals are using that 72-hour model with C19 patients who may need more time. Even before the coronavirus pandemic, some neurologists were questioning that model. In 2018 the American Academy of Neurology updated its guidelines for treating prolonged “disorders of consciousness,” noting that some situations may require more time and assessment.
  • Some patients, like Frank Cutitta, do not appear to have any brain damage. Whatever caused his extended period of unconsciousness cleared.
  • Unless a patient has previously specified that she does not want aggressive treatment, “we need to really go slow,” says Giacino, “because we are not at a point where we have prognostic indicators that approach the level of certainty that is necessary before making a decision that we should stop treatment because there is no chance of meaningful recovery.”
  • Doctors interviewed for this story urged everyone to tell their loved ones what you expect a “meaningful recovery” to include. If confronted with this situation, family members should ask doctors about their levels of certainty for each possible outcome.
  • Some medical ethicists are also urging clinicians not to rush when it comes to decisions about how quickly C19 patients may return to consciousness.
  • “A significant number of patients are going to have a prolonged recovery from the comatose state that they’re in,” says Dr. Joseph Fins, chief of medical ethics at Weill Cornell Medical College. “This is a time for prudence because what we don’t know can hurt us and can hurt patients.”
  • Leslie and Frank Cutitta have a final request: Wear a mask.
  • “This disease is nothing to be trifled with,” Leslie Cutitta says. “It’s a devastating experience.”
  • Frank Cutitta worries about all of the patients still suffering with C19 and those who have survived but have lasting damage.
  • “I’m not considering myself one of those,” he says, “but there are many, many people who would rather be dead than left with what they have after this.”

Source: They Survived The Ventilator. But Why Does Their COVID-19 Coma Persist? : Shots – Health News 

G. The Road Back?

1. New Thinking on Covid Lockdowns: They’re Overly Blunt and Costly 

  • In response to the novel and deadly coronavirus, many governments deployed draconian tactics never used in modern times: severe and broad restrictions on daily activity that helped send the world into its deepest peacetime slump since the Great Depression.
  • The equivalent of 400 million jobs have been lost world-wide, 13 million in the U.S. alone. Global output is on track to fall 5% this year, far worse than during the financial crisis, according to the International Monetary Fund.
  • Despite this steep price, few policy makers felt they had a choice, seeing the economic crisis as a side effect of the health crisis. They ordered nonessential businesses closed and told people to stay home, all without the extensive analysis of benefits and risks that usually precedes a new medical treatment.
  • There wasn’t time to gather that sort of evidence: Faced with a poorly understood and rapidly spreading pathogen, they prioritized saving lives.
  • Five months later, the evidence suggests lockdowns were an overly blunt and economically costly tool. They are politically difficult to keep in place for long enough to stamp out the virus. The evidence also points to alternative strategies that could slow the spread of the epidemic at much less cost. As cases flare up throughout the U.S., some experts are urging policy makers to pursue these more targeted restrictions and interventions rather than another crippling round of lockdowns.
  • “We’re on the cusp of an economic catastrophe,” said James Stock, a Harvard University economist who, with Harvard epidemiologist Michael Mina and others, is modeling how to avoid a surge in deaths without a deeply damaging lockdown. “We can avoid the worst of that catastrophe by being disciplined,” Mr. Stock said.
  • The economic pain from pandemics mostly comes not from sick people but from healthy people trying not to get sick: consumers and workers who stay home, and businesses that rearrange or suspend production. A lot of this is voluntary, so some economic hit is inevitable whether or not governments impose restrictions.
  • Disentangling voluntary and government-ordered effects is hard. One study, by economists Austan Goolsbee and Chad Syverson at the University of Chicago, says government restrictions account for just 12% of the decline in consumer mobility in the U.S.; another, by a team led by economists Kosali Simon at Indiana University and Bruce Weinberg at Ohio State, says they account for 60% of the loss of employment.
  • Still, because of the close connection between the pandemic and economic activity, many epidemiologists and economists say the economy can’t recover while the virus is out of control. “The virus is going to determine when we can safely reopen,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in April. The Federal Reserve said in late July that “the path of the economy will depend significantly on the course of the virus.”
  • Such statements leave wide open what represents an acceptable level of infection, which in turn determines what restrictions to impose. If the only acceptable level of infection were zero, lockdowns would have to be severe and potentially repeated, or at least until an effective vaccine or treatment comes along. Most countries have rejected that course.
  • Prior to C19, lockdowns weren’t part of the standard epidemic tool kit, which was primarily designed with flu in mind.
  • During the 1918-1919 flu pandemic, some American cities closed schools, churches and theaters, banned large gatherings and funerals and restricted store hours. But none imposed stay-at-home orders or closed all nonessential businesses. No such measures were imposed during the 1957 flu pandemic, the next-deadliest one; even schools stayed open.
  • Lockdowns weren’t part of the contemporary playbook, either. Canada’s pandemic guidelines concluded that restrictions on movement were “impractical, if not impossible.” The U.S. Centers for Disease Control and Prevention, in its 2017 community mitigation guidelines for pandemic flu, didn’t recommend stay-at-home orders or closing nonessential businesses even for a flu as severe as the one a century ago.
  • So when China locked down Wuhan and surrounding Hubei province in January, and Italy imposed blanket stay-at-home orders in March, many epidemiologists elsewhere thought the steps were unnecessarily harmful and potentially ineffective.
  • By late March, they had changed their minds. The sight of hospitals in Italy overwhelmed with dying patients shocked people in other countries. C19 was much deadlier than flu, it was able to spread asymptomatically, and it had no vaccine or effective therapy.
  • Taiwan, South Korea and Hong Kong set early examples of how to stop C19 without lockdowns. Their reflexes trained by SARS in 2003, MERS and avian flu, they quickly cut travel to China, introduced widespread testing to isolate the infected and traced contacts. Their populations quickly donned face masks.
  • Sweden took a different approach. Instead of lockdowns, it imposed only modest restrictions to keep cases at levels its hospitals could handle.
  • Sweden has suffered more deaths per capita than neighboring Denmark but fewer than Britain, and it has paid less of an economic price than either, according to JPMorgan Chase & Co.
  • Sweden’s current infection and death rates are as low as the rest of Europe’s. That has prompted speculation that it is pursuing herd immunity—the point when enough of the population is immune, due to prior exposure or vaccination, so that person-to-person transmission declines and the epidemic dies out. Currently there is no consensus on where that point is, in Sweden or elsewhere.
  • By March, it was too late for the U.S. to emulate the test-and-trace strategy of east Asia. The CDC had botched the initial development and distribution of tests, and limited testing capacity meant countless infections went undetected for months. President Trump continued to downplay testing, and even today the U.S. conducts fewer than 20 tests for every confirmed case, compared with more than 500 in Taiwan and South Korea at their peaks.
  • The Swedish strategy was also taken off the table. Britain ditched it in mid-March after a team of experts from London’s Imperial College predicted that in the absence of social distancing, 81% of the population would eventually be infected, while 510,000 people would die in Britain and 2.2 million in the U.S.
  • Those estimates may have been high. Some experts think it takes less than 81% of a population to reach herd immunity. Nonetheless, such predictions helped persuade leaders in Britain and the U.S. to lock down.
  • Yet at the outset, their goals were unclear, a confusion aggravated by the multitude of terms used. Officials sometimes said their goal was “bending” or “flattening the curve,” which originally meant spreading infections over time so the daily peak never overwhelmed hospitals. At other times they described their aims as “mitigation” or “containment” or “suppression,” often interchangeably.
  • “There have been few attempts to truly define the goal, and partly it’s because policy makers and epidemiologists haven’t thought well enough about the vocabulary to define what they mean or want,” said Dr. Mina, the Harvard epidemiologist.
  • A key determinant in an epidemic’s spread is the reproduction number, or “R value”: how many people each infected person goes on to infect. When R is above one, new infections continue until enough of the population has been infected or vaccinated to achieve herd immunity. When R is below one, new infections eventually fall to zero, although imported infections can trigger outbreaks. Dr. Mina said mitigation generally aims for an R of just above one, while suppression aims for an R of below one.
  • The U.S. never resolved “whether we were going for mitigation or suppression,” said Paul Romer, a Nobel laureate economist. Mitigation, he said, meant accepting hundreds of thousands of additional deaths to achieve herd immunity, which no leaders were willing to embrace. But total suppression of the disease “doesn’t make sense unless you’re going to stick with it as long as it takes.”
  • Some countries did achieve suppression through lockdowns. China wiped out the epidemic in Hubei province and has suppressed subsequent outbreaks elsewhere, with sweeping quarantine and surveillance methods that are difficult to replicate in Western democracies.
  • New Zealand imposed one of the most stringent lockdowns for two months. The country—relatively small and geographically isolated—went on to enjoy 102 days without a new case. Nonetheless, an outbreak this month prompted a reimposition of widespread restrictions.
  • The U.S. for the most part lacked China’s authoritarian bent and New Zealand’s patience. Asked in March if lockdowns would last months, President Trump replied: “I hope it disappears faster than that.” Indeed, at the end of March his health advisers suggested one more month of restrictions would be enough.
  • In mid-April, his health advisers issued guidelines for when states with lockdowns should reopen, including 14 days of declining cases and the ability to test and trace anyone with flu like symptoms. “The predominant and completely driving element that we put into this was the safety and the health of the American public,” Dr. Fauci told reporters.
  • But that same day Mr. Trump made it clear his priority was the economy: “A prolonged lockdown combined with a forced economic depression would inflict an immense and wide-ranging toll on public health,” he said. Within weeks he was praising states that had reopened despite not meeting the guidelines and was tweeting “LIBERATE” to supporters protesting lockdowns.
  • Many Republican governors prioritized their economies, but some Democrats more committed to lockdowns also struggled to stay the course. When California became the first state to issue a stay-at-home order on March 19, its Democratic governor, Gavin Newsom, said the goal was to “bend the curve.”
  • On May 7, he signaled an unusually ambitious goal: Only counties with zero deaths in the past two weeks and no more than one case per 10,000 residents could reopen ahead of schedule—criteria that 95% of the state couldn’t meet, according to the Los Angeles Times.
  • Mr. Newsom said science and data would dictate when the stay-at-home order was lifted. Economic and social pressures soon intruded, as county leaders pushed him to relax the criteria. On May 18 he did, dropping the no-death requirement and raising the case cutoff to 25 per 100,000.
  • Counties quickly began opening. A month later, California’s cases began surging again, far surpassing previous highs.
  • “I wouldn’t say our strategy ever really changed,” said Mark Ghaly, the state’s secretary of health and human services. “We needed to get [infections] low enough to where our systems can handle sick people.”
  • Dr. Ghaly said “there were conversations” about pursuing total suppression, as New Zealand had done, but that would have required an early, nationwide commitment, which wasn’t possible with very different views across the country.
  • The impact of lockdowns on families, the economy and mental health also mattered, he said: “When you see unemployment numbers going through the roof, businesses not just threatened week to week but potentially [never] being open again, you have to take that into account,” said Dr. Ghaly.
  • Dr. Mina of Harvard said the U.S. at the outset could have chosen to prioritize the economy, as Sweden did, and accept the deaths, or it could have chosen to fully prioritize health by staying locked down until new infections were so low that testing and tracing could control new outbreaks, as some northeastern states such as Rhode Island did.
  • Most of the U.S. did neither. The result was “a complete disaster. We’re harming the economy, waffling back and forth between what is right, what is wrong with a slow drift of companies closing their doors for good,” Dr. Mina said.
  • The experience of the past five months suggests the need for an alternative: Rather than lockdowns, using only those measures proven to maximize lives saved while minimizing economic and social disruption. “Emphasize the reopening of the highest economic benefit, lowest risk endeavors,” said Dr. Mina.
  • Social distancing policies, for instance, can take into account widely varying risks by age. The virus is especially deadly for the elderly. Nursing homes account for 0.6% of the population but 45% of Covid fatalities, says the Foundation for Research on Equal Opportunity, a free market think tank. Better isolating those residents would have saved many lives at little economic cost, it says.
  • By contrast, fewer children have died this year from Covid-19 than from flu. And studies in Sweden, where most schools stayed open, and the Netherlands, where they reopened in May, found teachers at no greater risk than the overall population. This suggests reopening schools outside of hot spots, with protective measures, shouldn’t worsen the epidemic, while alleviating the toll on working parents and on children.
  • If schools don’t reopen until next January, McKinsey & Co. estimates, low-income children will have lost a year of education, which it says translates into 4% lower lifetime earnings.

Research by Dr. Mina and others has shown that “super-spreader” events contribute disproportionately to infections, in particular dense indoor gatherings with talking, singing and shouting, such as at weddings, sporting events, religious services, nightclubs and bars.

Bars and restaurants accounted for 16% of Covid-19 clusters (five or more cases) in Japan; workplaces, just 11%. Bars, restaurants and casinos accounted for 32% of infections traced to multiple-case outbreaks in Louisiana.

Masks may be the most cost-effective intervention of all. Both the World Health Organization and the U.S. Surgeon General discouraged their use for months despite prior CDC guidance that they could limit the spread of flu by preventing the wearer from transmitting the disease.

The German city of Jena in early April ordered residents to wear masks in public places, public transit and at work. Soon afterward, infections came to a halt. Comparing it to similar cities, a study for the IZA Institute of Labor Economics estimated masks reduced the growth of infections by 40% to 60%.

  • Klaus Wälde, one of the authors, said nationwide mask wearing is helping the German economy return to normal while keeping infections low. Goldman Sachs Group Inc. estimates a universal mask mandate in the U.S. could now save 5% of gross domestic product by substituting for more onerous lockdowns.
  • Some epidemiologists and economists argue ramped-up testing could enable the economy to reopen safely without a vaccine. Mr. Romer estimates the U.S. could restore $1,000 in economic activity for every $10 spent on tests.
  • Dr. Mina pointed to a paper-strip test anyone can use to detect the virus in a sample of saliva in minutes. It is less accurate but far faster and cheaper than sending samples to labs, he said. If 50% to 60% of the population in hot spots took such a test every other day, the disease could be suppressed, he said.
  • Dr. Mina’s and Mr. Stock’s team has designed a “smart” reopening plan based on contact frequency and vulnerability of five demographic groups and 66 economic sectors. It assumes most businesses reopen using industry guidelines on physical distancing, hygiene and working from home; schools reopen; masks are required; and churches, indoor sports venues and bars stay closed.
  • They estimated in June that this would result in 335,000 fewer U.S. deaths by the end of this year than if all restrictions were immediately lifted. But they say the plan also would leave economic output 10% higher than if a second round of lockdowns were imposed.
  • “If you use all these measures, it leaves lots of room for the economy to reopen with a very small number of deaths,” Mr. Stock said. “Economic shutdowns are a blunt and very costly tool.”
  • The U.S. South and Southwest have provided some real-time experiments in targeted lockdowns. Arizona imposed a stay-at-home order in March and rescinded it in early May.
  • When cases soared, Republican Gov. Douglas Ducey resisted reimposing restrictions or requiring masks. He then eventually allowed cities to require masks, ordered bars, gyms, movie theaters and water parks to close and told restaurants to operate at no more than 50% capacity. Gatherings of more than 50 people were prohibited and masks strongly encouraged. But he didn’t lock down the entire state. Cases and hospitalizations have since fallen sharply to early May levels, or lower.
  • California, similarly, ordered indoor activities at restaurants, bars, museums, zoos and movie theaters to close in mid-July, but didn’t issue a stay-at-home order, prohibit outdoor activities or suspend elective surgery, as it had in March and April. Cases have begun to drop, while hospitalizations have declined 35% since their July peak.
  • “In March, people didn’t realize the benefits of mask use,” said Dr. Ghaly, the state’s secretary of health and human services. “The evidence on being outdoors rather than indoors is quite compelling.” Compared to April, “We know so much more.”

Source: New Thinking on Covid Lockdowns: They’re Overly Blunt and Costly 

H. Back to School!?

1. Updated CDC School Guidance 

  • The US CDC published updated guidance regarding school openings. The updated guidance provides additional recommendations for a myriad of topics, including ventilation, food service, and mask use as schools continue to prepare and implement their plans to start the 2020-21 school year. 
  • The guidance also expands on previous iterations regarding students with “special healthcare needs and disabilities” with a new section dedicated to these challenges. Schools may need to develop individualized plans for some students and staff, including those with limited mobility, those with visual or hearing impairments, those with underlying health conditions, or those who may have difficulties understanding or adapting to new routines. 
  • The information notes that some individuals may struggle with social distancing or isolation or mask use, or they may need additional visual or verbal reminders or assistance implementing the school’s social distancing protocols. The information also links to guidance regarding protections related to service animals.
  • Another notable addition is guidance regarding how schools should address infected students or staff. The document advises schools to coordinate with local health officials to address the issue of suspending in-person classes and events. The CDC notes that short-term building closures may be necessary to allow health officials time to assess the situation, and local health officials can help determine whether longer-term interruptions to in-person classes and activities may be necessary. 
  • If schools are cohorting students, particularly if they are cohorted in specific areas, it may be possible to limit interruptions to just those groups or spaces, rather than the entire school.

Source: Johns Hopkins COVID-19 Update (8/24/20)

I. Advances in Technology & Equipment

1. Reusable mask is designed to fix the 28 major problems with the N95  

  • During the SARS outbreak in Toronto in 2003, healthcare workers raised concerns about N95 masks, saying that the respirators were uncomfortable to wear for long shifts and could lead to headaches and shortness of breath. In the aftermath of SARS, the U.S. government issued a report arguing that the masks needed to be redesigned for future epidemics, citing 28 ways the masks needed to improve. Then the fear of pandemics faded from most people’s minds. But Tobias Franoszek and Natasha Duwin were working on making a new mask that fulfilled those benchmarks.
  • “N95 masks and mask technology hadn’t really changed in a very long time,” says Franoszek, cofounder of Octo Safety Devices, the company making the new mask, called the Octo Respirator Mask, or ORM. Three years ago, long before the emergence of C19, Franoszek and Duwin started exploring alternatives, acquiring the rights to a new mask design that eventually became the ORM.
  • Unlike an N95, the mask is designed for reuse and can be sterilized by boiling. “The idea of having something be discarded after one use is anathema to us,” says Duwin. The antimicrobial filter inside is also reusable. The mask can be sterilized dozens of times, so if someone uses it infrequently—say, for weekly trips to the grocery store—it could last a year or more. In times between epidemics, it can be safely stored on a shelf for as long as 10 years without degrading. It filters out 99% of harmful particles, going beyond the 95% threshold required for N95 masks. Critically, it’s also designed to be comfortable to wear, even if someone has to keep it on for a 12-hour shift at a hospital.
  • In the SARS epidemic, “the statistics came back that 43% of casualties were healthcare workers,” says Franoszek. “That was surprising—healthcare workers are the ones that are very aware of the dangers of a virus because they’re physically treating it. They had a lot of anecdotal evidence of people just pulling off their masks, saying, ‘I can’t take this anymore.’”
  • N95 respirators weren’t originally used in healthcare—they were most commonly used in construction and manufacturing—but began to be used in hospitals in the early 1990s during a resurgence of tuberculosis. They were never designed to be particularly comfortable for hours of use, either for someone working in construction or in a hospital. The new mask, on the other hand, is made of soft silicone, making it much more comfortable. The silicone also seals tightly to the face without the complicated adjustments that are necessary to make an N95 mask fit; an N95 mask typically takes training and practice to learn to wear correctly.
  • A pleated filter increases airflow, making it more breathable while still protecting both the wearer and the people around them. In total, the mask addresses 26 out of the 28 recommendations in the government report on improving respirators. (The company plans to address the other two—making it possible to put the mask on without self-contaminating and making the mask transparent—but wanted to bring the mask to market as quickly as possible.) [Note: The mask costs $107.00 and can be purchased at https://octosafety.com/products/octo-respirator]
  • At the start of 2020, the company had planned to finish the design and begin selling it through distributors for a variety of uses, from industry to healthcare, late in the year. As the new coronavirus spread, they rushed to bring it to market earlier, selling both to healthcare workers and the general public, even though they hadn’t intended to be a direct-to-consumer brand (though the company is still waiting on FDA or NIOSH approvals). “We started hearing about this strange thing happening in China and how they had closed down a city,” says Duwin. “We looked at each other and we were like, Oh my God, we have this thing in our hands that can really help people.”

Source: The reusable Octo Safety Device is designed to outperform the N95

J. Practical Tips & Other Useful Information

1. It’s Not Enough to Wear a Mask, You Have to Wear It Right 

Tips Wearing COVID-19 Mask


Use these helpful tips to properly wear and store your mask

  • How to wear your mask
  • Wear your mask secure over your mouth and nose.
  • Wear your mask secure over your mouth and nose.
  • How to store your mask when going to the bathroom, taking a drink or eating
  • Place your mask on a clean paper towel. (Exterior of the mask facing down with the ties placed away from the inside.)
  • Store your mask in a clean paper bag.
How Not to Wear a Mask
  • How NOT to wear your mask
  • Do not wear your mask under your mouth.
  • Do not pull your mask under chin, even to drink.
  • Do not wear your mask on your elbow.
  • Do not hang your mask from one ear.

Source: Simple COVID-19 Tips for Wearing a Face Mask: It’s Not Enough to Wear a Mask, You Have to Wear It Right

K. Johns Hopkins COVID-19 Update

August 24, 2020

1. Cases & Trends

Overview
  • The WHO C19 Dashboard reports 23.31 million cases (253,963 new) and 806,410 deaths (5,501 new) as of 8:30am EDT on August 24.
  • Total Daily Incidence (change in 7 day average incidence; change in rank, if applicable)
  • 1.  India: 65,526 new cases per day (+3,728)
  • 2.  USA: 42,763 (-8,438)
  • 3.  Brazil: 37,941 (-5,598)
  • 4.  Colombia: 10,402 (-1,148)
  • 5.  Peru: 8,340 (+65)
  • 6.  Argentina: 6,815 (+59)
  • 7.  Spain: 6,177 (+2,113; ↑ 3)
  • 8.  Mexico: 5,429 (-554; ↓ 1)
  • 9.  Russia: 4,842 (-203; ↓ 1)
  • 10.  Philippines: 4,050 (-427; ↓ 1)
  • Per Capita Daily Incidence (change in 7 day average incidence; change in rank, if applicable)
  • 1.  Maldives: 263 new daily cases per million population (+66; ↑ 5)
  • 2. Peru: 253 (+2; ↓ 1)
  • 3.  Bahrain: 219 (+16; ↑ 2)
  • 4. Colombia: 204 (-23; ↓ 1)
  • 5. Brazil: 179 (-26; ↓ 1)
  • 6.  Israel: 173 (+13; ↑ 1)
  • 7.  Panama: 164 (-83; ↓ 5)
  • 8.  Bahamas: 163 (+12; ↑ 2)
  • 9.  Argentina: 151 (+2; new)
  • 10.  Costa Rica: 150 (+5; new)
  • India reported its highest average daily incidence to date—65,526 new cases—and it remains on track to surpass the global record for global average incidence, which is currently held by the US (67,374 on July 23). The US and Suriname fell out of the top 10 in terms of per capita daily incidence and were replaced by Argentina and Costa Rica. The Maldives and Peru are the only 2 countries currently averaging more than 250 daily cases per million population.
United States
  • The US CDC reported 5.64 million total cases (45,265 new) and 175,651 deaths (1,006 new). In total, 19 states (no change) are reporting more than 100,000 cases, including California with more than 600,000 cases; Florida and Texas with more than 500,000; New York with more than 400,000; and Georgia and Illinois with more than 200,000. The US is averaging fewer than 1,000 deaths per day for the first time since July 27.
  • Several US territories are exhibiting extremely high per capita daily incidence. The US Virgin Islands is reporting 332 new daily cases per million population, which would be #1 globally. Puerto Rico is reporting 194 new daily cases per million population, which would put it at #5 globally, falling between Colombia and Brazil. Guam is also reporting 222 new daily cases per million population, which would be #3 globally; however, this appears to be driven largely by a spike of 105 new cases reported on August 21 that resulted in Guam’s daily incidence increasing by a factor of 4 in just one week. Guam’s daily incidence does appear to be increasing, but potentially not quite at this rate over the longer term.
  • The Johns Hopkins CSSE dashboard reported 5.72 million US cases and 176,978 deaths as of 1:30pm EDT on August 24.

2. Convalescent Plasma 

  • The US FDA issued an Emergency Use Authorization (EUA) for convalescent plasma as a C19 treatment. Plasma is a component of blood that contains antibodies, and the plasma from individuals who recover from SARS-CoV-2 could be administered to C19 patients in order to boost immune response. Prior to the EUA, some patients were able access convalescent plasma through compassionate use programs and randomized clinical trials, but the EUA will make the treatment more broadly available to C19 patients. 
  • The FDA previously postponed issuing the EUA to allow for further analysis of recently published clinical trial data, and several senior health experts at the NIH, including Dr. Anthony Fauci and Dr. Francis Collins, indicated that more robust clinical data was needed in order to better understand the potential benefits. As we covered previously, the study in question was conducted by the Mayo Clinic. While the study included 35,000 participants and provided promising results, it did not involve a placebo control group, which complicates efforts to interpret the findings and draw conclusions about the treatment’s efficacy. Previous studies have demonstrated the treatment’s safety in C19 patients.
  • Numerous health experts have expressed concern about the data underlying the EUA as well as statements made in the EUA announcement and by senior US government officials, including Secretary of Health and Human Services Dr. Alex Azar. Both the EUA press release and Secretary Azar indicate that convalescent plasma reduces mortality by 35%; however, it is unclear exactly what these statements are based on. Several experts have asserted that these statements overestimate or misrepresent the drug’s effect. Rather than a groundbreaking treatment, it may be more likely that convalescent plasma provides incremental benefit to C19 patients. 
  • Additionally, some experts have expressed concern that the decision could have been politically motivated, particularly in light of recent comments by President Donald Trump, who suggested that the FDA was delaying trials and approval for candidate treatments and vaccines until after the upcoming presidential election. To some, the circumstances surrounding the convalescent plasma EUA are reminiscent of the EUA that the FDA issued for hydroxychloroquine, which was widely promoted by President Trump. Ultimately, the FDA rescinded the EUA after additional data indicated that it was not effective as a C19 treatment.

3. Vaccine Use 

  • China reportedly announced that it has been administering its coronavirus vaccine to certain high-risk populations since late July, raising concerns about the use of a vaccine in the general public prior to the completion of robust clinical trials. 
  • If true, this would make China the first country to use a coronavirus vaccine in the public, beating Russia’s effort to deploy its Sputnik V vaccine by at least several weeks. 
  • China previously announced that it would administer the vaccine to its military, and it is unclear why China waited several weeks before publicly announcing the vaccination program. Both Russia and China are moving ahead with public vaccination programs for vaccines that do not appear to have progressed through the full, traditional evaluation and authorization process. This highlights concerns that the various health, economic, and political pressures associated with the C19 pandemic could lead to accelerated review processes being insufficient to effectively characterize the safety and efficacy for candidate vaccines and other drugs in order to make them available more rapidly.
  • The controversial announcement by China follows a recent report that Papua New Guinea forced a flight containing Chinese mine workers to turn around due to concern that the workers had received a coronavirus vaccine as part of a previously unannounced trial. 
  • Earlier in August, a group of Chinese workers received a coronavirus vaccine shortly before departing China as part of a clinical trial, and government officials in Papua New Guinea detained the travelers when they landed because no trial was registered or approved in Papua New Guinea. The company that owns the mine sent a letter to officials in Papua New Guinea stating that the workers had been vaccinated and that the vaccine could potentially result in false positive results for coronavirus tests. It is unclear what vaccine the workers who arrived previously received or if the workers onboard the diverted flight were vaccinated.

4. Remdesivir Trial 

  • Results from another clinical trial of remdesivir provide additional evidence that the drug can provide treatment benefit, but it not necessarily provide additional clarity on the drug’s benefit for C19 patients. The study, published in JAMA, included 584 patients across more than 100 hospitals in the US, Europe, and Asia. 
  • The patients were randomly assigned to receive a 5-day or 10-day treatment course of remdesivir or the current standard of care, and the researchers evaluated the patients’ health using a 7-point ordinal scale—1 corresponding to death and 7 corresponding to patient recovery and discharge. The study had a control group, but it was not a placebo-controlled trial, which poses challenges to interpreting the results. The study identified an improvement in clinical condition for patients who received the 5-day course of treatment but not for the 10-day course, compared to the control group. The researchers explicitly note that, while the difference was statistically significant, “the difference was of uncertain clinical importance.”
  • An accompanying commentary highlights this study’s findings in the context of previous studies, several of which have also yielded statistically significant but clinically ambiguous results. The authors describe the implications of certain study design choices—such as clinical metrics or endpoints, patient population, and placebo-controlled versus open label—can have on the results. While this most recent study does provide valuable information on the treatment benefit of remdesivir, it remains clear that further study is needed in order to better characterize its effects and determine how best to use it in the C19 pandemic.

5. Auckland Extends Lockdown 

  • Earlier today, New Zealand Prime Minister Jacinda Ardern announced that the current level of social distancing restrictions in Auckland will be extended beyond the previously scheduled termination date. The decision aims to “provide a greater degree of certainty” that community transmission in Auckland remained at a low level before moving forward with efforts to relax existing restrictions in order to better ensure that it can remain at the lower Alert Level following the transition. The Auckland area is now scheduled to move from Alert Level 3 to Alert Level 2 on August 31, which will permit schools to reopen and restaurants and bars to begin reopening, among other changes. As Auckland transitions to Alert Level 2, there will be additional restrictions beyond the normal Alert Level 2 standards, including on the size of some gatherings and continued mandatory mask use.
  • Auckland’s outbreak began 2 weeks ago, after more than 100 days without documented domestic transmission in New Zealand. Since then, health officials have identified at least 101 associated cases, including 8 in the past 24 hours. Notably, Māori and Pacific Peoples comprise 87% of identified cases in the current outbreak, compared to only 19% for New Zealand’s entire national epidemic. 
  • The majority of cases early in New Zealand’s epidemic, before successfully interrupting domestic transmission, were of European descent, but the current outbreak is disproportionately impacting lower-income racial and ethnic minority communities. These disparities mirror those observed in many other countries, including systemic racism, high prevalence of underlying health conditions, high-density or crowded living conditions, and barriers to accessing health care. Health officials and other experts have placed increased importance in communicating and educating the affected populations and promoting recommendations, including testing and social distancing.
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