Recent Developments & Information
June 22, 2020
Reliable information is the best tool available to protect your family from the pandemic and its shockwaves
“Only a small percentage of people have been infected, the infection fatality rate is higher than seasonal flu, and this terrible disease is unlikely to go away on its own. In short, the pandemic is far from over.”
Dr. Samir Bhatt, Faculty of Medicine at Imperial College of London
“The Spanish Flu mostly disappeared from the United States in 1918, gone overseas. And then in the fall and winter, it came roaring back and a third of the deaths took place in a little tiny period between September and December. So I’m very worried that something like that could happen this fall and winter and that we’re not mentally prepared for it.”
Donald G. McNeil Jr., science and health report for the NY Times
“We have learned a great deal about COVID-19 and, across the nation cases we are plateauing. There are still outbreaks, but we have a better capacity to handle them with early case identification, contact tracing, and isolation.”
Dr. Redfield, CDC Director
Index
A. The Pandemic As Seen Through Headlines
B. Numbers & Trends
C. Conflicting Data & Different Opinions
New Cases Have Been Rapidly Increasing in the US, So Why Are New Deaths Decreasing?
Coronavirus is weakening, could disappear on its own (!)
D. Potential Treatments
Antibody Treatment from Cow Plasma to Begin Human Trials
E. New Scientific Findings & Research
Antibodies in C19 patients fade quickly
Studies in humanized mice and convalescent humans yield a coronavirus antibody cocktail
Antibody cocktail more effective at preventing mutations
Gut microbiome may influence the severity of C19
Italy’s sewage water shows coronavirus present prior to reported outbreak in Wuhan
F. Concerns & Unknowns
Diabetics have increased risk of severe illness, and twice the risk of death
Ignoring cancer care now may trade one public health crisis for another
G. Technology vs. Coronavirus
Red Alert: Wearable Early Warning Systems for C19 [Recommended]
H. Testing
A Negative C19 Test Can Be Misleading
I. Back to School!?
Expecting Students to Play It Safe Is a Fantasy
As fall tuition comes due, so do more questions
J. Projections & Our (Possible) Future
Herd Immunity Is Not The Answer
How many needless C19 deaths were caused by delays in responding? Most of them
K. Pandemic Economy
5 charts that track how the U.S. economy is recovering from coronavirus
L. Johns Hopkins COVID-19 Update
M. Links to Other Interesting Stories
Notes:
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- We do not endorse, and may not agree with, any opinion or view included in this update. We include a wide spectrum of opinions and views as we believe that it gives perspective on what people are thinking and may give insights into our future.
A. The Pandemic As Seen Through Headlines
(In no particular order)
- WHO warns of “a new and dangerous phase” of the pandemic as cases grow in 81 countries
- WHO reports largest single-day increase in coronavirus cases on June 19
- We Will Be Living With the Coronavirus Pandemic Well Into 2021
- Wall Street Expects a Covid-19 Vaccine Before the U.S. Election
- Coronavirus vaccine by year’s end no longer ‘aspirational’ but ‘likely,’ says top general
- Young people drive new coronavirus spikes
- Masks Are Mandated Even in Red States, With Cases Soaring
- In countries keeping the coronavirus at bay, experts watch U.S. case numbers with alarm
- CDC predicts that US death toll could reach 145,000 by July 11
- Brazil passes one million cases after reporting a one-day total of more than 54,000
- Officials call for greater vigilance, as Florida and South Carolina set repeated highs for new daily cases
- New Study Shows COVID-19 Wreaked Havoc on America’s Minority-Owned Businesses
- Food Inequality Crisis Deepens in U.S. Under Pandemic’s Pressure
- Young Americans Struggle to Find Jobs, Internships This Summer
- Students Face $10 Trillion in Lost Earnings Due to Pandemic
- Face mask requirements grow contentious, with States and businesses taking divergent paths
- Swimming Holes Fill the Void as Virus Closes Pools
- Apple to Close Some U.S. Stores Again as Covid-19 Spikes
- Lockdowns May Be Driving Another Virus Wave in Asia: Dengue Fever
- Italy’s Sewage Held Virus in December
- Virus Drives Online Sales to Record, and Some of That Will Stick
- A French official affirms that a kiss will still be a kiss — in the movies
- As New York City prepares for a broader reopening, the mayor says: Take it slow
- Cruise lines won’t sail from U.S. ports until September 15
- Prime Minister Shinzo Abe of Japan lifted a virus-related ban on domestic travel
- Britain reduced its Covid-19 alert level to three from four, which paves the way for a gradual easing of social-distancing measures
- South Korea reported 67 more cases, as a second wave of infections continued to spread in the Seoul metropolitan area
- NBA restart worries grow as Florida coronavirus cases surge
- Brazil passes 50,000 coronavirus deaths as outbreak worsens
- Dutch police detain 400 after protest over coronavirus restrictions
- Coronavirus indicators on ‘right path’ as NYC enters Phase 2 reopening
- NY Gov. Cuomo warns of second coronavirus wave when states reopen ‘politically’
- NYC’s Army Of 3,000 COVID-19 ‘Contact Tracers’ Have Accomplished Surprisingly Little
- California reports record jump in cases
- German “R” rate nears 3 as meat processing plant outbreak intensifies
- Tulsa reports record jump in infections day after Trump rally
- At least 12 states report 7-day averages at record highs
- Spain lifts restrictions on tourism as economy reopens
- South Korea bars travelers from Pakistan, Bangladesh
- More Studies Find Coronavirus Spread In China Much Earlier Than Beijing Admits
- As new cases surge in the U.S., the White House acknowledges preparing for a fall wave
- India’s hospitals, crammed with Covid patients, turn others away
- Wildlife trade spreads coronaviruses as animals go to market
- Can gay bars, an anchor of N.Y.C. nightlife, survive the pandemic?
- Alarm is building over an explosion of cases in Houston
- Nursing homes are forcing vulnerable residents into homeless shelters and rundown motels
- China hopes testing will curb new coronavirus outbreak in Beijing
- New York’s positive coronavirus test results hold steady at 1 percent
- NHL sets date for playoffs, players forbidden from nightclubs
- UK preps for reopening pubs in next phase of easing coronavirus lockdown
- Strippers make bank online during the pandemic
- Alarming amount of animals in Vietnam have a coronavirus: study
- Brazil tops 1 million coronavirus cases, second only to US
- California surpasses New Jersey for state with second-most coronavirus cases
- MLB closes all 30 spring training camps
- Some star athletes are stranded overseas as events resume in the U.S.
- For small towns in the West, canceled rodeos are more than just forgone sports events
- Three pro sports teams shut down facilities in Florida, amid worries over player safety
- Older adults may be left out of some clinical trials for a vaccine or treatment
- Chinese scientists see a European link to the Beijing outbreak, but the WHO sees less
- D.C. May Begin Phase 2 Reopening Monday
- EEOC: Employers Can’t Make Employees Take Coronavirus Antibody Test
- After Calling It ‘Very Grim,’ China Declares Beijing Coronavirus Outbreak ‘Under Control’
- Japan lifts a domestic travel ban despite new infections
- Britain didn’t want Silicon Valley’s help on a tracing app, but now it does
- College and professional sports in the U.S. stumble toward a renewal that may not come in 2020
- 77-Year-Old Barber Wins Again: Michigan Gov. Whitmer Caves on Attempt to Strip License
- 47% of US homeowners seriously mulling selling home over coronavirus money woes
- Carnival loses $4.4 billion as coronavirus sinks cruise industry
- NYC playgrounds to reopen June 22 as city enters Phase 2 of reopening
- NASA Astrobiologists Progressing on Antiviral Solutions for COVID-19
- Massachusetts orders utilities cut off at gym defying lockdown—so the owner gets generators and porta potties
- Cheap booze, hard seltzer sales spike during COVID-19
- ‘Bold and The Beautiful’ Using Blowup Doll for Sex Scenes Amid Coronavirus
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 = 9,038,809 (+1.5%)
- New Cases = 130,254 (-26,668)
- Growth Rate of New Cases (7 day average) = 0.6%
- New Cases (7 day average) = 146,323 (+828)
Observations:
- The highest number of new cases since the beginning of the pandemic occurred on June 19 (181,648 new cases)
- Although the number of new cases has decreased by more than 50,000 over the weekend (weekend reporting is typically lower), it seems likely that the number of new cases will continue to trend higher
US Cases & Testing:
- Total Cases = 2,356,657 (+1.1%)
- New Cases = 26,079 (-7,309)
- Percentage of New Global Cases = 20% (+0.1%)
- Growth Rate of New Cases (7 day average) = 3.2%
- New Cases (7 day average) = 27,663 (+845)
- Total Number of Tests = 28,491,990 (+519,127)
- Percentage of positive tests (7 day average) = 5.2% (+0.2%)
Observations:
- New cases declined by approx. 7,500 over the weekend, but are still high (and lower numbers are often reported over the weekend)
- It is too early to tell if the decrease in new cases over the weekend is a temporary decline or the start of trend (in light of the recent surge in new cases in some States, a temporary decline seems more likely to us)
- Daily testing has exceeded 500,000
2. Deaths
Worldwide Deaths:
- Total Deaths = 469,604 (+0.7%)
- New Deaths = 3,338 (-1,090)
- Growth Rate of New Deaths (7 day average) = 0.2%
- New Deaths (7 day average) = 4,753 (+10)
Observations:
- New deaths have decreased sharply over the last 5 days, declining from 6,599 new deaths on June 16 to 3,338 on June 21
- Even with the recent declines in new deaths, the 7 day average has generally been trending higher since May 26.
- It is too early to tell if the recent declines in new deaths are a trend or a temporary decline.
US Deaths:
- Total Deaths = 122,247 (+0.2%)
- New Deaths = 267 (-306)
- Percentage of Global New Deaths = 8% (-6.8% since 6/18)
- Growth Rate of New Deaths (7 day average) = -1.3%
- New Deaths (7 day average) = 628 (-8)
Observations:
- Lowest number of new deaths since March 27
- New deaths have been generally trending down since 4/21 (7 day average of new deaths has decreased from 2,214 on 4/21 to 628 on 6/21, a decrease of 71.6%)
C. Conflicting Data & Different Opinions
1. New Cases Have Been Rapidly Increasing in US, So Why Are New Deaths Decreasing?
Background
- New cases generally declined from April 24 to June 9, after which new cases generally began rising after June 9
- New cases on June 21 reached 26,079 (which was a significant decrease from the preceding 2 days)
- The 7 day average of new cases has increased from 21,265 on June 9 to 27,227 on June 21, an increase of 28%
- The 7 day average of new cases on 6/21 was 27,227, which is 16% less than the highest 7 day average of new cases of 32,425 on April 10
- New deaths have generally been declining since April 21 even as new cases have started to recently increase
- Since the increase in new cases started on June 10, the 7 day average of new deaths has decreased from 982 new deaths on 6/10 to 626 new deaths on 6/21, a decrease of 36.3%
- Deaths are a lag indicator, which means that new deaths are expected to increase after an increase in cases
- In a study reported in Lancet on March 12, WHO reported that the time between symptom onset and death ranged from about 2 weeks to 8 weeks (see: the Lancet here.)
- In another study published in Lancet on March 30, the mean period of time between the start of symptoms and death has been estimated as 17.8 days (see the Lancet here.)
- However, new deaths began declining on April 21, which was 3 days before the peak number of new cases occurred on April 24, which is inconsistent with expectations
Analysis
- While there has been a rough correlation between new cases and new deaths, new deaths have been declining faster than new cases
- New cases decreased by 48.8% between its peak on April 24 and June 9 whereas new deaths decreased by 63.6% between its peak on April 21 and June 9
- From June 9 to June 20, the 7 day average of new cases increased by 28% while the 7 day average of new deaths decreased by more than 36% — that is a non-correlated divergence of 54%
- Although daily numbers of cases and deaths can be volatile, and new cases have unquestionably been trending higher over the last 11 days (notwithstanding the decrease in new cases over the weekend) and new deaths have been trending lower for almost 2 months, including during the recent period during which new cases have been surging.
- A number of explanations have been suggested, including:
- First, perhaps new deaths will increase as a result of the recent spike in new cases. Although we have not seen a corresponding increase in the number of new deaths, perhaps deaths will increase in the near future. We’ll know a lot more in 4 to 6 weeks (if the average number of days between symptom onset and death is around 18 days, then we should start to see some significant spikes in new deaths within the next week or so, but with 18 day being an average, we probably should have already started to see some increases in new deaths).
- Second, we know more about C19 now than we did a few months ago, and perhaps improved treatments are reducing the number of new deaths. This explanation will make more sense if new hospitalizations increase with increases in new cases. There does appear to be increased hospitalizations in some States that are experiencing increases in new cases, but the data is not always available on a timely basis. So, we will monitor a few States to evaluate to what extent hospitalizations increase as new cases increase.
- Third, there may be far more asymptomatic people than we think. The CDC has estimated that up to 35% of infections are asymptomatic. Other has found that 40 to 45% of infections are asymptomatic (see 40–45% who contract new coronavirus are asymptomatic). Another paper estimated that up to 80% of infections are asymptomatic (although high percentages of asymptomatic cases can substantially increase the spread of C19, it also means that a high percentage of people may not be at risk, which could explain the divergence between new cases and new deaths).
- Fourth, some have argued that an increase in new cases AND a decrease in deaths indicates that healthier people are becoming infected as they engage in more activities while vulnerable people are being more cautious. As heathier people are much less likely to die, that is a potential explanation, which also provides a potential path for reopening our economy (e.g., economies are reopened for healthy people with few restrictions and more vulnerable people take additional precautions).
- Fifth, some have suggested that the virus has become less lethal (see next story). While there research and expert opinions to support that theory, most experts appear to believe that is not the case. Although this seems implausible, it would explain some of the inconsistencies in the numbers and trends and it is possible, so we will continue to track.
- At this time, while we concede that the first explanation is plausible, we believe that a combination of the second, third and fourth explanations is a more plausible explanation, but time will tell.
2. Coronavirus is weakening, could disappear on its own
- An Italian infectious disease doctor believes the coronavirus has become less dangerous — and could disappear on its own without a vaccine.
- Dr. Matteo Bassetti, the head of the infectious diseases clinic at the San Martino hospital, said the virus appears to have become less potent, possibly due to genetic mutations.
- “The clinical impression I have is that the virus is changing in severity,” Bassetti told the outlet.
- “In March and early April the patterns were completely different. People were coming to the emergency department with a very difficult to manage illness and they needed oxygen and ventilation, some developed pneumonia.”
- But he said in the past month, “the picture has completely changed in terms of patterns.”
- “It was like an aggressive tiger in March and April but now it’s like a wild cat,” Bassetti said. “Even elderly patients, aged 80 or 90, are now sitting up n bed and they are breathing without help. The same patients would have died in two or three days before.”
- He said one of the reasons for the virus becoming weaker could be that it has mutated in response to social distancing measures.
- “I think the virus has mutated because our immune system reacts to the virus and we have a lower viral load now due to the lockdown, mask-wearing, social distancing,” he said. “We still have to demonstrate why it’s different now.”
- It’s possible that the virus will be eradicated before researchers find a vaccine, he said.
- “We have fewer and fewer people infected and it could end up with the virus dying out,” Bassetti said.
- But another expert was less optimistic about the prospect of the virus disappearing soon, saying it could take years, the outlet reported.
- “I don’t expect it to die out that quickly,” said Dr. Bharat Pankhania, a professor at the UK’s University of Exeter Medical School, according to the report.
- “It will if it has no one to infect. If we have a successful vaccine then we’ll be able to do what we did with smallpox. But because it’s so infectious and widespread, it won’t go away for a very long time.”
Source: Coronavirus is weakening, could disappear on its own: Italian doctor
D. Potential Treatments
1. MMR Vaccine Could Protect Against the Worst C19 Symptoms – “A Low-Risk-High-Reward Preventive Measure”
- Administering the MMR (measles, mumps, rubella) vaccine could serve as a preventive measure to dampen septic inflammation associated with C19 infection, say a team of experts in this week’s mBio, a journal of the American Society for Microbiology. Long-time collaborators and spouses Dr. Paul Fidel, Jr., Department Chair, Oral and Craniofacial Biology, and Associate Dean for Research, Louisiana State University Health School of Dentistry and Dr. Mairi Noverr Professor of Microbiology & Immunology at Tulane University School of Medicine in New Orleans co-authored the perspective article based on ideas stemming from research in their labs.
- Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to C19, say the researchers.
- “Live attenuated vaccines seemingly have some nonspecific benefits as well as immunity to the target pathogen. A clinical trial with MMR in high-risk populations may provide a low-risk-high-reward preventive measure in saving lives during the C19 pandemic,” said Dr. Fidel. “While we are conducting the clinical trials, I don’t think it’s going to hurt anybody to have an MMR vaccine that would protect against the measles, mumps, and rubella with this potential added benefit of helping against C19.”
- Mounting evidence demonstrates that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing trained nonspecific innate immune cells for improved host responses against subsequent infections. Live attenuated vaccines induce nonspecific effects representing “trained innate immunity” by training leukocyte (immune system cells) precursors in the bone marrow to function more effectively against broader infectious insults.
- In Dr. Noverr’s laboratory, in collaboration with Dr. Fidel, vaccination with a live attenuated fungal strain-induced trained innate protection against lethal polymicrobial sepsis. The protection was mediated by long-lived myeloid-derived suppressor cells (MDSCs) previously reported inhibiting septic inflammation and mortality in several experimental models. The researchers say that an MMR vaccine should be able to induce MDSCs that can inhibit or reduce the severe lung inflammation/sepsis associated with C19. Mortality in C19 cases is strongly associated with progressive lung inflammation and eventual sepsis.
- Recent events provide support for the researchers’ hypothesis. The milder symptoms seen in the 955 sailors on the U.S.S Roosevelt who tested positive for C19 (only one hospitalization) may have been a consequence of the fact that the MMR vaccinations are given to all U.S. Navy recruits. In addition, epidemiological data suggest a correlation between people in geographical locations who routinely receive the MMR vaccine and reduced C19 death rates. C19 has not had a big impact on children, and the researchers hypothesize that one reason children are protected against viral infections that induce sepsis is their more recent and more frequent exposures to live attenuated vaccines that can also induce the trained suppressive MDSCs that limit inflammation and sepsis.
- The researchers propose a clinical trial to test whether the MMR vaccine can protect against C19, but in the meantime, they suggest that all adults, especially health care workers and individuals in nursing homes get the MMR vaccine. “If adults got the MMR as a child they likely still have some level of antibodies against measles, mumps, and rubella, but probably not the myeloid-derived suppressor cells,” said Dr. Fidel. “While the MDSCs are long-lived, they are not life-long cells. So, a booster MMR would enhance the antibodies to measles, mumps, and rubella and reinitiate the MDSCs
- We would hope that the MDSCs induced by the MMR would have a fairly good life-span to get through the critical time of the pandemic.”
2. Plans to Begin Human Trials that Use Antibody Treatment from Cows
- What may be an effective weapon against the novel coronavirus is coming from an unlikely source: a barn in South Dakota.
- SAb Biotherapeutics, a South Dakota-based clinical-stage biopharmaceutical company, plans to begin human trials of a C19 antibody treatment using plasma from cows.
- To do so, scientists genetically engineered the cattle’s immune system to produce human antibodies that have the ability to fight against the coronavirus.
- The cows are essentially injected with a coronavirus vaccine, prompting their immune system to try and ward off the infection, NPR explained. The cows then “produce a specifically targeted high-neutralizing antibody that can be used in patients,” Dr. Eddie Sullivan, CEO and co-founder of SAb Biotherapeutics, told NPR.
- Antibodies are produced by immune systems after the body detects the presence of a foreign substance otherwise known as an antigen. Antibodies then latch onto antigens in an effort to remove them from the body.
- The hope is that these targeted high-neutralizing antibodies will either slow an infection in someone who is already sick or prevent someone from becoming infected after being exposed to the virus, NPR explained.
- An antibody “therapy for C19 could prove critical in combatting this pandemic as it could potentially treat severely ill patients and provide protective antibodies for front-line responders, mission-critical staff, and high-risk populations, such as the elderly and immune-compromised,” Sullivan explained in a company statement.
- Companies typically turn to cultured cells or tobacco plants when manufacturing antibodies for treating or preventing diseases, according to Science Magazine. However, unlike other companies, SAB has been leveraging dairy cows to develop treatments for infectious diseases, with the coronavirus being its latest hurdle, the outlet explained.
- SAb has previously developed more than a dozen effective antibodies in response to outbreaks including Ebola, Zika, Dengue and Hantavirus.
- The company’s production plans have been supported by the U.S. Department of Health and Human Services and the U.S. Department of Defense, NPR reported.
- Researchers from the company claim cows have a more robust immune response than humans. Additionally, using mammals eliminates the need for the firm to identify, screen, and draw blood from recovering volunteers.
- The approach may open the door to “medicines that are potentially more potent, safer, and longer-lasting than current antibody therapies,” SAb said.
- Aside from that, cows offer a lot of plasma: “Between 30 and 45 liters of plasma every month from each animal,” Sullivan told NPR.
- The “therapeutic candidate for C19 deploys the same natural immune response to fight the disease as recovered patients, but with a much higher concentration of targeted antibodies,” the company said.
- SAb says it’s “on track” to initiate clinical trials for its potential C19 treatment this summer but did not specify how many people would participate or how long the trial would last.
Source: https://www.foxbusiness.com/lifestyle/cow-plasma-used-for-potential-covid-19-antibody-treatment
E. New Scientific Findings & Research
1. Antibodies in C19 patients fade quickly
- A new study from China showed that antibodies faded quickly in both asymptomatic and symptomatic C19 patients during convalescence, raising questions about whether the illness leads to any lasting immunity to the virus afterward.
- The study, which focused on 37 asymptomatic and 37 symptomatic patients, showed that more than 90% of both groups showed steep declines in levels of coronavirus–specific immunoglobulin G (IgG) antibodies within 2 to 3 months after onset of infection, according to a report published yesterday in Nature Medicine. Further, 40% of the asymptomatic group tested negative for IgG antibodies 8 weeks after they were released from isolation.
- The authors said the findings suggest that it could be risky to assume that recovered patients are immune to reinfection, which may have implications for how long to maintain physical distancing restrictions.
Antibody levels dropped 70%
- Among the main findings was that IgG levels in 93% of the asymptomatic group and 97% of the symptomatic group declined greatly during the early convalescent phase (by 8 weeks after release from the hospital). Antibody levels dropped by 71.1% in asymptomatic patients and 76.2% in the symptomatic group.
- “Moreover, 40.0% of asymptomatic individuals, but only 12.9% of symptomatic individuals, became seronegative for IgG” during that time, the report says.
- The researchers also found declines in specific neutralizing antibodies (antibodies that can neutralize a pathogen on their own, without help from other elements of the immune system), but the declines were not nearly as large as with IgG.
- Decreases in the neutralizing antibodies were seen in 81% of the asymptomatic group and 62% of the symptomatic group. The median decreases in antibody level were 8.3% in the asymptomatic group and 11.7% in the symptomatic patients.
- The report also notes that IgG levels were significantly higher in the symptomatic patients than the asymptomatic ones in both the acute and convalescent phases of infection.
Longer shedding in asymptomatic group
- In other findings, the researchers said the asymptomatic patients shed the virus significantly longer than the symptomatic patients—a median of 19 days versus 14 days. But they cautioned that detectable viral shedding does not necessarily mean that the viral particles shed were infectious.
- The investigators also measured the levels of a number of cytokines and chemokines in the patients and concluded that “the asymptomatic individuals had a reduced inflammatory response characterized by low circulating concentrations of cytokines and chemokines.”
- The authors observe that their findings contrast with what’s known about the duration of antibodies to two other key coronaviruses, SARS-CoV, which causes severe acute respiratory syndrome (SARS) and MERS-CoV (Middle East respiratory syndrome coronavirus). Previous findings indicate that antibodies to those viruses last at least a year and often longer, they said.
- In combination with certain previous findings on C19 antibodies, the researchers concluded that their results “might indicate the risks of using C19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups and widespread testing.”
- The study did not address cellular immunity to C19—that is, immune responses involving T-cells rather than antibodies. Some previous studies have found SARS-CoV–specific T-cells in high percentages of convalescent C19 patients.
Source: Chinese study: Antibodies in COVID-19 patients fade quickly
2. Studies in humanized mice and convalescent humans yield a coronavirus antibody cocktail
Abstract
- Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola – one from genetically-humanized mice, and the other from a human survivor.
- In our research, we used both humanized mice and convalescent patients to generate antibodies against the coronavirus spike protein, yielding a large collection of fully-human antibodies that were characterized for binding, neutralization and three dimensional structure.
- Based on these criteria, we selected pairs of highly-potent individual antibodies that simultaneously bid the receptor-binding domain of the spike protein, providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for escape mutants that might arise in response to selective pressure from a single antibody treatment.
For full article, see: Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail
3. Antibody cocktail more effective at preventing mutations
Abstract
- Antibodies targeting the spike protein of the coronavirus present a promising approach to combat the C19 pandemic; however, concerns remain that mutations can yield antibody resistance.
- We investigate the development of resistance against four antibodies to the spike protein that potently neutralize the coronavirus, individually as well as when combined into cocktails.
- Although these antibodies remain effective against spike variants that have arisen in the human population, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such mutations also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein.
- The escape of mutations will lead to resistance to the antibodies.
- Cocktail therapy may provide a powerful way to minimize mutational escape by the coronavirus; in particular, our studies point to the potential value of antibody cocktails in which two antibodies were chosen so as to bind to distinct and non-overlapping regions of the viral target (in this case, the RBD of the spike protein), and thus require the unlikely occurrence of simultaneous mutations at two distinct genetic sites for viral escape.
- A clinical candidate selection criterion for broad potency that includes functional assessment against naturally circulating sequence variants, as well as inclusion of multiple antibodies with non-overlapping epitopes, may provide enhanced protection against loss of efficacy.
- Future in vivo animal and human clinical studies need to pay close attention to possible emergence of escape mutants and potential subsequent loss of drug efficacy.
For full study, see : Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
4. Gut microbiome may influence the severity of C19
- The risk of severe C19 infection is more common in those with high blood pressure, diabetes and obesity, conditions that are all associated with changes to the composition of the gut microbiome — the community of bacteria, viruses and fungi that live in the intestines. This raises the question of whether the gut microbiome has a role in dictating C19 severity.
- One of the reasons for an abnormal, overreactive immune response lies in the gastrointestinal tract. Millions of interactions are constantly occurring between the immune system and trillions of non-dangerous microbes that live within the body. These interactions educate the immune system in how to function and, importantly, in how not to overreact to infectious microbes. Could this help explain why some people are more likely to develop uncontrolled inflammation upon C19 infection?
- The gut microbiome is the community of micro-organisms living inside the gastrointestinal tract, mostly in the large bowel. The microbiome contains bacteria, fungi (yeast), viruses and protozoa, all of which contribute to maintaining a balanced ecosystem and human health. These microbes collectively perform many beneficial functions, including educating the immune system.
- When studying the microbiome, scientists examine the composition (what is there) and function (what are they doing) of this ecosystem. We have learned that both composition and function of the gut microbiome are important features linked to human health. In certain conditions, the balance of the gut microbiome composition and function is disrupted in a way that leads to disease, a phenomenon called microbiome dysbiosis.
- There is accumulating evidence from animal and human studies that gut microbiome dysbiosis has a causal role in metabolism dysregulation manifested as diabetes and obesity — the risk factors of severe C19 disease.
Is gut microbiome predisposing patients to severe C19?
- The gut microbiome regulates host defences against viral infections including respiratory viruses, such as influenza virus. This occurs through the activation of immune antiviral mechanisms and the prevention of excessive inflammation.
- Different species of the gut microbiome have pro- or anti-inflammatory properties and play different roles in regulating the immune system. In the context of C19, a recent preprint study (not yet peer reviewed) showed that specific members of the gut microbiome were associated with severe disease and with immune markers known to be elevated in severe disease. The association of these gut bacteria with the immune markers was even higher than that of the known risk factors of C19 severity: age and obesity.
- Further work is needed to confirm that pro-inflammatory microbial species can contribute to the immune responses that make severe C19 more likely, but based on what we know about the microbiome, this is certainly a possibility. This also could mean that beneficial gut microbiome species, the type that promote low inflammation, have the potential to prevent or remediate the immune alterations that lead to severe C19.
Potential for treatments and prevention
- The research community is working very hard to develop and test safe and effective vaccines and treatments against C19. Tapping into the potential of the gut microbiome is another avenue that we can pursue to identify potential safe and affordable probiotics for prevention and treatment. This is not unprecedented in the context of viral respiratory diseases: probiotics and prebiotics can affect the immune response to the flu vaccine, and may improve outcomes in flu-like illnesses.
- Until effective treatments are available, “mind your microbes” and maintain a healthy lifestyle.
Source: Gut reaction: How the gut microbiome may influence the severity of COVID-19
5. Italy’s sewage water shows coronavirus present prior to reported outbreak in Wuhan
- Italian researchers have found traces of the coronavirus in sewage wastewater that indicates that the virus may have been in circulation since December 2019. This controversial discovery shows that even before the first case was reported in Wuhan, China, in late December 2019, the virus had already arrived in northern Italy.
The C19 pandemic and Italy
- The first local case reported in Italy (an infected case with no travel history to a country where there is an outbreak) was recorded in the town of Codogno in the Lombardy region. Lombardy was marked as a “red zone” or containment zone on the 21st of February. Nine other towns in Lombardy and neighboring Veneto reported cases, after which the country had to be locked down early in March.
- Italian researchers from the Italian National Institute of Health or the Istituto Superiore di Sanità (ISS) collected forty samples of sewage water from wastewater treatment plants located in northern Italy between October 2019 and February 2020.
- A report was released this week on the findings of this analysis of sewage water from various water treatment plants. From the samples obtained in Milan and Turin on the 18th of December 2019, the team found the presence of the coronavirus.
- The team said that samples of the virus were found in sewage water samples from Bologna, Milan, and Turin in January and February 2020. The sewage samples were taken in October and November 2019, however, had tested negative for the virus.
- This study is the first that shows the presence of the virus even before it appeared in the news, and even before the first case was identified in China. This could mean that the spread of the virus had started earlier than thought until now. Researchers called these results of “strategic importance.”
- Scientists from the Netherlands, France, Australia have also conducted similar studies and detected traces of the virus. This could help trace the original spread of the virus, feel researchers. Researchers on this team also feel that detecting the virus before it was declared a pandemic in March 2020 could help trace the spread of the virus.
- For example, a study published in May 2020 by French researchers showed that there was a case of C19 in France on the 27th of December 2019, nearly a month before the nation had reported the first case. The first confirmed case of C19 was reported from Spain in late February, early March. A recent study revealed traces of the virus in sewage water in the country in mid-January in Barcelona.
- Noel McCarthy, from Warwick Medical School, Britain, said that this study and its results are “reliable evidence of cases of C19 being present there at that time”. He added that this shows the presence of the virus even before it began to spread rapidly. Professor of epidemiology and data processing Rowland Kao, Edinburgh University, Scotland, said that this shows that the disease may be in circulation earlier than thought. He added, “(This finding) does not on its own, however, tell us if that early detection was the source of the vast epidemic in Italy, or if that was due to a later introduction into the country.”
- Study author La Rosa added that these results do not “automatically imply that the main transmission chains that led to the development of the epidemic in our country originated from these very first cases.” The team of researchers now plan on a pilot study starting July to see the presence of the virus in wastewater in the tourist resorts. Lucia Bonadonna, director of the department of environment and health, said that the ISS has proposed to the Italian health ministry a countrywide study to monitor the presence of the virus in wastewater.
- This finding comes off the back of other shocking research out of Ecuador that found the coronavirus in river water, creating a significant transmission risk in developing countries with inadequate sanitation facilities.
Source: Italy’s sewage water shows SARS-CoV-2 present prior to reported outbreak in Wuhan
F. Concerns & Unknowns
1. Diabetics have increased risk of severe illness, and twice the risk of death
- People with Type 1 diabetes may be at a high risk of developing severe symptoms and illness from C19, according to a new study published in Diabetes Care.
- Diabetes is generally known to weaken the immune system, making it harder to protect against viral infections like C19. Viruses, like the novel coronavirus, may also aggravate pre-existing diabetic systems leading to added challenges managing blood sugar levels and worse outcomes.
- Researchers found that about half of the people in the study with Type 1 diabetes and suspected or confirmed C19 infections had abnormally high blood sugar — highlighting how C19 can complicate blood sugar control in Type 1 diabetic patients.
- Having consistently high blood sugar can be a sign of diabetic ketoacidosis, a potentially fatal diabetic complication that is characterized by high blood sugar and low insulin levels. It is commonly triggered by infections.
- In the study, almost half of all confirmed C19 cases also developed diabetic ketoacidosis,
- “This points to the need for people with diabetes to check their blood glucose often, and to keep blood glucose in good control.” said Dr. K.M Venkat Narayan, professor of global health and epidemiology at Emory University, who was not involved in the study.
- He added, “People with diabetes, in general, are at increased risk of adverse COVID complications, and at more than twice the risk of death from COVID than people without diabetes.”
- There are two main types of diabetes: Type 1 and Type 2. Type 1 diabetes is an autoimmune condition, which means that the immune system attacks the body’s own cells and impairs its ability to produce insulin, a hormone that helps to control blood sugar levels. Blood sugar regulation is a complicated process, affected by multiple factors such as food, sleep, stress and illness. Type 2 diabetes, the much more common form of the disease, usually presents itself in adults and can often be controlled by healthy eating and exercise.
- This study only included patients with Type 1 diabetes and a suspected or confirmed case of C19.
- “So far, most of the studies published have lumped together all types of diabetes. We know these conditions can be very different and we need to study them separately,” said Dr. Fernando Ovalle, director of the division of endocrinology, diabetes and metabolism at the Birmingham School of Medicine, University of Alabama, who was not involved in the study.
- Dr. Mary Pat Gallagher, director of pediatric diabetes at NYU Langone Health and co-author of the study said that from the data they have the risks of complications, such as high blood sugar and diabetic ketoacidosis with C19, are probably similar to those seen in other viral illnesses.
- However, “COVID is a more serious infection than influenza,” Narayan said.
- More research is needed, according to Ovalle. The study was fairly small; most people studied were in their early 20s and did not examine how the severity of C19 symptoms compared to people without Type 1 diabetes.
- “Much more research is needed before we can know for sure what the true risks are, particularly for Type 1 diabetes,” he said.
- Dr. Osagie Ebekozien, author of the paper and vice president at T1D Exchange, added, “As we collect additional data, we will be able to provide more insights on factors that contribute to increased risks of hospitalization and adverse outcomes as a result of C19 for people with Type 1 diabetes.”
- Regardless, the CDC said that diabetes, “including type 1, type 2, or gestational, may put people at higher risk of severe illness from C19,” and patients should take extra precautions. The agency recommends taking diabetes pills or insulin as usual, testing and keeping track of blood sugar every four hours, and having at least a two-week supply of diabetes pills or insulin.
- “High glucose levels may be one factor contributing to excess risk from COVID, and therefore, attention to glucose control is key,” said Narayan.
- Experts advise that diabetics should talk to their physicians if their medications need adjustment. “It is usually possible to prevent diabetic ketoacidosis if the higher insulin requirements that are often seen with viral illnesses are addressed early in the process,” said Gallagher.
- A healthy lifestyle with regular exercise, balanced diet, regular sleep and stress management all help with diabetes control and “may also help boost defenses against COVID,” said Narayan.
- Amid the pandemic, disruptions to work, care and daily routines make it harder to maintain good blood sugar control. Experts advise vigilance and care: Take safety measures to avoid C19, check blood sugar levels more frequently if feeling sick and do not hesitate to seek a physician’s assistance. Serious complications are preventable with early intervention and responsible diabetes management.
Source: Type 1 diabetics may be at high risk for severe illness related to coronavirus: Study
2. Ignoring cancer care now may trade one public health crisis for another
- The director of the National Cancer Institute believes the C19 pandemic is posing a danger to cancer patients across a wide spectrum of care and research. People — and their health care providers — are postponing screening measures like mammograms and colonoscopies. Fewer cancers are being diagnosed, and treatment regimens are being stretched out into less frequent encounters. Clinical trials have seen patient enrollment plummet.
- An NCI model looking just at breast cancer and colorectal cancer predicts there will be 10,000 excess deaths in the U.S. over the next 10 years because of pandemic-related delays in diagnosing and treating these tumors. That’s about a 1% increase over the number of expected deaths during that time span, with most of the rise coming in the next two years. And that assumes cancer care depressed by the coronavirus rebounds after six months.
- “We think that [mortality] estimate we provided is very conservative and likely to grow if we continue to postpone screening treatment and other cancer care,” Sharpless told STAT. “We’re very worried about the consequences of … delaying therapy on our patients.”
- Now is the time to reopen cancer care, Sharpless said. Hospitals that are now seeing fewer C19 patients are beginning to ramp up care and patients shouldn’t be afraid to go there, if they observe reasonable precautions, he said.
- “Clearly, postponing procedures and deferring care as a result of the pandemic was prudent at one time, but the spread, duration, and future peaks of C19 remain unclear,” he wrote in an editorial published in this week’s Science. “However, ignoring life-threatening non-C19 conditions such as cancer for too long may turn one public health crisis into many others. Let’s avoid that outcome.”
- “We now have a lot more experience than we did a few months ago, starting to understand its route of transmission and patterns of spread,” he said in the interview. “I think now we can be judicious in the use of testing and mask wearing and good social distancing and certain [other] behaviors.”
- What if there’s a second wave in the fall?
- “We can open hospitals and worry about a second wave. I think it’s possible to do both. We have to,” he said. “To do otherwise, we’re going to trade different public health emergencies. So I think we can’t delay cancer care forever.”
- NCI estimates a drop of 75% in mammograms since March, which may be conservative, Sharpless said, compared to the 95% cited by Epic, the electronic health records vendor. Whether “upstaging,” the term for diagnosing cancer at a later stage, will become a problem depends on the cancer. Some cancers are called indolent because their growth can be slow enough that a three- or six-month delay won’t matter. But in lung cancer, for which there is no screening equivalent to mammography or colonoscopy, even a month’s delay can be harmful.
- “Three months is a lot of time and six months — well, then you start to see a 1% increase in mortality,” he said.
- Certain adaptations made by hospitals treating cancer patients and researchers running cancer clinical trials could continue, including telemedicine visits for some care and oral consent over the phone rather than in person to participate in trials.
- “The coronavirus pandemic is a public health event that everyone should be worried about and should behave appropriately, including people who run hospitals. They need to preserve capacity and take a proper pandemic response,” Sharpless said. “But the things we do to diminish our risk are not without impact on other areas. Public health and cancer outcomes are inextricably linked.
- “We have to realize the tradeoffs we make when we work on one versus the other and find that right balance.”
Source: Ignoring cancer now may trade one health crisis for another: NCI chief
G. Technology vs. Coronavirus
1. Red Alert: Wearable Early Warning Systems for C19
- Initially, the makers of devices such as the Apple Watch, the Fitbit fitness tracker, and the Oura ring Hollmen wears played up their ability to help users count steps, stay active, or monitor sleep. It turns out these gadgets may also be useful in detecting illness.
- Scientists around the world are racing to discover if wearable technology can tell whether users have contracted coronavirus days before they have a dry cough or any other telltale indicators. In cases of C19, changes to heart rate, for example, often appear before more noticeable symptoms, such as fever.
- Wearable devices could act as critical early warning systems, predicting and helping prepare for the next wave of C19.
- “There’s an asymptomatic phase in individuals where people are infected by the virus, a three- to five-day period where there are no symptoms whatsoever,” says Dr. Ali Rezai, executive chairman of the West Virginia University Rockefeller Neuroscience Institute. “What would you do with the information if you knew on your phone app that in three days there’s a 90% chance you’re going to have the symptoms?” You might stay home, he says, or take other steps to protect people around you.
- Research has shown wearable data could discover health problems including high blood pressure, heart arrhythmias, and early-stage cancer. A study published in the Lancet Digital Health journal in January set the stage for using the same approach to anticipate the spread of C19.
- It found that data from a Fitbit could predict the number of influenza-like illnesses in the general population as well as or better than the Centers for Disease Control and Prevention’s epidemiological models. Eric Topol, director of the Scripps Research Translational Institute, says that wearables could work even better for the coronavirus. “It has the advantage of being simple, continuous, and passive,” he says. “The virus isn’t going away. So we have to have a really good tracking system.”
- Public-health officials are relying on testing programs, combined with contact tracing, to measure how widely outbreaks might spread. Fitness trackers, though, could do some of that work—and relieve the burden on budget-strapped states struggling to train tens of thousands of contact tracers.
- For his research, Rezai and his colleagues recruited more than 800 health-care workers and first responders to wear the Oura ring and share the biometric data it collects through sensors touching the skin. Using an app, participants also take part in daily surveys that measure stress, anxiety, memory, and other indicators. From his office in Morgantown, W.Va., Rezai demonstrates how this information is analyzed, sharing an online dashboard with a reporter 2,600 miles away.
- Sorted in varying hues of magenta and turquoise, cornflower and emerald, the screen gives an overview of how research subjects are feeling at any given moment, with the colors representing such data as different symptoms or subject groups. A word cloud shows the prevalence of signs ranging from cough and runny nose to fatigue and shortness of breath, while pie charts display C19 cases by age and gender. A map homes in on regions of West Virginia and southwestern Pennsylvania and highlights symptoms by ZIP code. One area lights up in bright red, an indicator of a handful of potentially worrisome symptoms.
- Projects like this are being carried out widely. Scripps Research Institute is monitoring the heart rates of about 30,000 volunteers with an array of fitness trackers to look for early signs of disease. A Stanford study is similarly measuring heartbeats among people who are exposed to C19 or are at high risk of contracting the disease. The University of California at San Francisco, meanwhile, initially armed 2,000 health-care workers with Oura rings, later opening the study to thousands of ring-wearing members of the general public.
- Kimberly Noel is a physician who’s been taking part in the UCSF study for several weeks. A telemedicine specialist interested in how sensors can pick up information from the body, Noel also helped launch a similar research project at Stony Brook University. “The more people you have, the better,” she says. “It’s more than a pretty ring.”
- The data is of limited use on an individual level; there are plenty of reasons for an elevated heart rate that have nothing to do with C19. But when taken together, large numbers of data points can act as a smoke signal for disease.
- Jennifer Radin, who leads the Scripps study, says wearables have the advantage of offering information that’s nearly real-time and more geographically specific than other disease projections. As additional data is collected, projections will only get better, allowing officials to act faster, she says.
- Already, researchers have seen promising evidence of how the tracking might assist in predicting new outbreaks. The Rockefeller Neuroscience Institute says its platform can predict coronavirus-related symptoms as long as 3 days before they show up, with 90% accuracy. Michael Snyder, a Stanford geneticist who’s leading the university’s study, shared early results with Bloomberg Businessweek that showed heart rate anomalies were being detected at or before C19 diagnoses 75% of the time in a 19-person group. In one instance, his team was able to predict infection 9 days in advance. Heart rate is stacking up to be a very good indicator: “You can’t miss that signal,” he says.
- Any added evidence would jump-start adoption of wearables, according to NPD Group analyst Eddie Hold. Las Vegas Sands Corp. plans to outfit 1,000 employees with Oura rings for illness-risk detection as casinos reopen. Although the segment has been growing in popularity over the past decade, only 1 in 5 adults uses a fitness tracker and fewer wear a smartwatch, Hold says. “If they can prove that one of these wearable devices can help,” he says, “it will be a huge boon.”
Source: Bloomberg Hyperdrive
H. Testing
1. A Negative C19 Test Can Be Misleading
- You go out to a bar with friends this week, and you’re planning to visit your elderly relatives in a few days. You feel healthy, and you even get a C19 test out of caution. The result comes back negative. Is it safe to go?
- Not exactly, experts say. How well C19 tests work in people who feel healthy is still a key unknown of the pandemic. The test may overlook the small but growing amounts of virus in someone who has not yet developed symptoms, who could still go on to spread C19 without knowing it. So as Americans weigh the risks of attending protests, rallies, birthday parties, dinners, and all the social gatherings that make up normal life, they will have to contend with the uncertainty that a negative test result does not rule out infection. “If they go do a risky contact, they can’t get a ‘Get out of jail free’ card. They can’t just get tested and feel fine,” says A. Marm Kilpatrick, a disease ecologist at UC Santa Cruz.
- Understanding false negatives from C19 tests is especially important because people who do not yet know that they’re sick play a major role in the spread of C19. A study based on data in and around China suggests that 44% of transmission comes from pre-symptomatic cases. The United States has not isolated people who say they feel sick as aggressively as China has, so it likely has a higher proportion of symptomatic transmission, says Benjamin Cowling, an epidemiologist at the University of Hong Kong, who co-authored the study. But China’s experience makes clear that simply isolating people once they are sick is not enough. “We can’t ignore pre-symptomatic transmission,” Cowling says. “Even if you manage to stop some of the transmission from going on by doing isolation cases, you still will have this presymptomatic transmission, which keeps the epidemic going.”
- It’s still unclear how good C19 tests are at finding these pre-symptomatic cases, but the timing of the test matters. As soon as the coronavirus finds its way into a new host, it hijacks cells to copy itself. The amount of virus builds over this time, peaking at or right before symptom onset, which can take two to 14 days but usually takes an average of five or six. Accordingly, public-health authorities have advised getting tested about four days after exposure.
- This is a reasonable recommendation, given the knowns, but surprisingly little data exists on how early C19 tests can detect infection before symptom onset. One model using C19 cases from seven previously published studies suggests that the false-negative rate is 100% on day one of exposure, which falls to 38% on day five (when symptoms on average appear) and then a minimum of 20% on day eight. But in combing the literature, the researchers behind this model found only one case where a patient was tested before feeling sick—as part of a cluster at a chalet in the French Alps. Moreover, the model doesn’t address a whole other set of people who never develop symptoms at all. “It gave no information about people who are permanently asymptomatic,” Justin Lessler, an epidemiologist at Johns Hopkins University who co-authored that study, told me.
- More data is likely to come soon. On Tuesday, the FDA released recommendations for labs and manufacturers that want to validate C19 tests in people who don’t have symptoms. (Currently, no tests are FDA-authorized for screening asymptomatic people.) Testing large numbers of asymptomatic people—such as by pooling samples—to identify potential silent carriers will also be an essential part of the reopening strategy for schools and businesses.
- For individuals, however, the FDA cautions that negative results do not rule out infection. It asks that asymptomatic tests include this statement: “Negative results must be considered in the context of an individual’s recent exposures, history, presence of clinical signs and symptoms consistent with C19.” And this, in the face of imperfect C19 tests, is key to interpreting a negative result. It depends on your probability of having C19 in the first place.
- Consider again the decision to visit elderly relatives after a negative test. “If you have symptoms or you work in a place where you’re at high risk for exposure, then even with a negative test, you might want to think really hard about it,” Steven Woloshin, a co-director of the Center for Medicine and Media at the Dartmouth Institute, explained to me. “If you’re at low risk because you live in some remote area, you’re practicing social distancing, you always wear a mask, and you feel fine,” a negative test is probably a true negative. So even with widespread testing, social distancing and masks will continue to be important for controlling the spread of C19.
Source: What a Negative COVID-19 Test Really Means
I. Back to School!?
1. Expecting Students to Play It Safe Is a Fantasy
Safety plans border on delusional and could lead to outbreaks of C19 among students, faculty and staff
By Laurence Steinberg, professor of psychology at Temple University
- A number of American colleges and universities have decided to bring students back to campus this fall, believing they can diminish the risk of coronavirus transmission if everyone wears masks, uses hand sanitizer and social distances. Some schools also plan to reconfigure dorms to create family-sized clusters of uninfected students, who could socialize in relative safety, if only with their suitemates.
- These plans are so unrealistically optimistic that they border on delusional and could lead to outbreaks of C19 among students, faculty and staff.
- My skepticism about the strategies under consideration is not based on videos of college students frolicking on Florida’s beaches when they were explicitly told to avoid large gatherings. Rather, it comes from more than 40 years teaching and researching young people.
- Most types of risky behavior — reckless driving, criminal activity, fighting, unsafe sex and binge drinking, to name just a few — peak during the late teens and early 20s. Moreover, interventions designed to diminish risk-taking in this age group, such as attempts to squelch binge drinking on campus, have an underwhelming track record. There is little reason to think that the approaches proposed to mitigate transmission of the coronavirus among college students will fare any better. A series of studies that compare the ways in which young people and adults think and make decisions about risk-taking confirms this.
- The late-adolescent peak in risky behavior has been found pretty much around the world. Although risky behavior is more common in some countries than others, the heightened risk-taking characteristic of adolescents, relative to adults, is more or less universal. My colleagues and I recently completed a study of more than 5,000 people between the ages of 10 and 30 from 11 different countries (including both Western and non-Western ones). Respondents answered a series of questions about the extent to which they had engaged in various types of risk-taking. Consistent with large-scale epidemiological studies, we found a peak in risk-taking somewhere between age 20 and 24 in virtually every country.
- Our team has also conducted experiments in which we test participants on various risk-taking tasks under controlled conditions, which allows us to rule out any age differences in real-world risk-taking that might be caused by environmental factors, such as opportunity or cultural norms. As in our survey studies, risk-taking peaked during adolescence. Other studies, using different samples, have reached similar conclusions.
- We’ve also conducted a series of experiments designed to identify just what it is about college-age individuals that accounts for their relatively greater propensity to take risks. Three factors appear to be most important.
- First, this is the age at which we are most sensitive and responsive to the potential rewards of a risky choice, relative to the potential costs. College-age people are just as good as their elders at perceiving these benefits and dangers, but compared with older people, those who are college-aged give more weight to the potential gains. They are especially drawn to short-term rewards.
- Second, college-aged people have more trouble exercising self-control than do those in their late 20s and beyond, an age difference that is amplified when people are emotionally aroused. Under calm conditions, college-age individuals can control their impulses as well as their elders, but when they are emotionally aroused, they evince the poor self-control of teenagers.
- Finally, college-age people show more activation of the brain’s reward regions and are more likely to take risks when they are with their peers than when they are alone. There are no such effects of peers among people who are past their mid-20s.
- Not all adolescents are risk-takers, of course, and not all adults are risk-averse. But it’s hard to think of an age during which risky behavior is more common and harder to deter than between 18 and 24, and people in this age group make up about three-fourths of full-time American undergraduates.
- And, in case it’s been a long time since you were in college, let me remind you that there is no shortage of rewarding temptations, emotional arousal or unsupervised peer groups on the typical college campus. It’s one of those perfect storms — people who are inclined to take risks in a setting that provides ample temptation to do so.
- My pessimistic prediction is that the college and university reopening strategies under consideration will work for a few weeks before their effectiveness fizzles out. By then, many students will have become cavalier about wearing masks and sanitizing their hands. They will ignore social distancing guidelines when they want to hug old friends they run into on the way to class. They will venture out of their “families” and begin partying in their hallways with classmates from other clusters, and soon after, with those who live on other floors, in other dorms, or off campus. They will get drunk and hang out and hook up with people they don’t know well. And infections on campus — not only among students, but among the adults who come into contact with them — will begin to increase.
- At that point, college administrators will find themselves in a very dicey situation, with few good options.
- I look forward to a time when we are able to return to campus and in-person teaching. But a thorough discussion of whether, when and how we reopen our colleges and universities must be informed by what developmental science has taught us about how adolescents and young adults think. As someone who is well-versed in this literature, I will ask to teach remotely for the time being.
Source: Opinion | Expecting Students to Play It Safe if Colleges Reopen Is a Fantasy
2. As fall tuition comes due, so do more questions
- The first installment of my daughter’s fall 2020 college tuition payment came due last week. I paid it with a bit of reservation and a lot of faith.
- Faith that the University of Michigan will prioritize safety, whatever return-to-class looks like.
- Faith that UM’s plan to offer at least some in-person instruction is worth the high cost of living in Ann Arbor.
- Faith that my daughter’s senior-year classes, and ultimately her liberal arts degree, will serve her well in the chaotic and uncertain time in which she will graduate.
- Plenty of parents, and students, are wondering what college will look like post-COVID, from cramped dorm rooms to cavernous lecture halls. My daughter is lucky to have her own room in a house off campus, but many others are questioning whether the traditional — and expensive — communal college experience makes sense during a pandemic.
- Meanwhile, we wait for any scrap of news about fall plans. But specifics are hard to come by as universities try to balance safety with the potential blow to their bottom line.
- Coronavirus has forced some creativity: Eastern Michigan University, for example, is offering single dorm rooms at a much lower cost this year to lure students to campus during a time when enrollment is already declining. Will it work? “It’s hard to read the tea leaves in the middle of a pandemic,” EMU President James Smith told Crain’s reporter Kurt Nagl last week.
- Michigan State is trying to keep newly admitted freshmen engaged by allowing them to get a low-cost jump on their studies. For the first time, the university is offering freshmen and transfer students the chance to enroll in up to two summer courses at a substantial discount. “We know the last few months have been stressful … We hope this opportunity helps you engage with the Spartan family right away,” an assistant dean, James Lucas, wrote in a June 10 email to students.
- Grand Valley State says it’s already well-suited to social distancing given that 80% of its dorms offer private rooms and bathrooms. And in a June 2 memo to students, UM promised “a public health-informed fall semester on our three campuses safely and with as much in-person instruction as possible.”
- More details are coming — presumably. Many universities are reluctant to be specific as the state gradually re-opens, no doubt fearful of a second wave of infections. That’s understandable but doesn’t help students and parents make critical financial and career-planning decisions now.
- UM’s fall payment plan, which spreads the semester cost into monthly installments, starts billing in June. But what are we actually paying for? How many classes will meet in person, and what kind of labs, clubs and extracurricular opportunities will still be available? Again — faith.
- This spring’s virtual coursework was disappointing for my Wolverine. Her professors were engaged and accommodating, but given the cost of attending a Big Ten university, remote lectures are no substitute for in-person learning.
- All of which spells trouble for traditional higher education in Michigan, particularly smaller and more affordable regional institutions.
- A Brookings Institution report last week showed the pandemic has hit those campuses especially hard. Declining enrollment is hammering places like Western Michigan, Central Michigan and EMU. Unlike their bigger counterparts, they have fewer options to shore up their budgets. State aid to Michigan’s 12 universities increased by just 0.9 percent in the 2019-20 fiscal year, well below the 1.75% rate of inflation.
- Universities are under more scrutiny than ever as families make tough choices about cost, debt and the value of a four-year degree. If COVID drives even more students away, some may not survive the long slog toward a vaccine.
- My daughter and her classmates debated taking the term or even the year off if classes remained online-only. UM’s signal toward in-person instruction convinced her, reluctantly, that returning made sense. She’s so close to the finish line.
- Like so much else in These Uncertain Times, only time will tell.
Source: Commentary: As fall tuition comes due, so do more questions
J. Projections & Our (Possible) Future
1. Herd Immunity Is Not The Answer
- There is no evidence that declines in transmission of the coronavirus in some countries are the result of herd immunity, says new analysis undertaken by researchers from Imperial College London and the University of Oxford.
- Herd immunity is achieved when a significant proportion of the population is protected from infection, either through becoming immune following a previous infection, or through other natural means, such as cross protection from exposure to related viruses, or through a vaccination program.
- The researchers looked at whether the observed decline in C19 cases and deaths in many countries in Europe, North America and parts of Asia could be the result of herd immunity.
- If this was the case, there would be roughly similar rates of C19 mortality, and levels of antibodies to the coronavirus across different countries. It would also imply that the virus might have a low fatality rate, as the deaths recorded would only make up a small proportion of those who had been infected.
- However, the researchers found little evidence for herd immunity and concluded that the decline in cases and deaths was a result of lockdowns, behavioral shifts, social distancing and other interventions.
- This means that the epidemic is still at a relatively early stage and that a large proportion of the population in these areas remain susceptible to the virus.
- The authors suggest that no country has yet seen infection rates sufficient to prevent a second wave of transmission if lockdowns and social distancing measures were relaxed without other measures in place.
- The authors also concluded from data on deaths and antibody levels from Europe that the infection fatality rate is high, at between 0.5 – 1%, compared with less than 0.1% fatality rate for seasonal flu.
- The study is published in a peer-reviewed correspondence article in The Lancet by researchers from the MRC Centre for Global Infectious Disease Analysis, Jameel Institute (J-IDEA) at Imperial College London, and the University of Oxford.
- Study author Dr. Samir Bhatt, from NIHR Imperial BRC Infection & Antimicrobial Resistance Theme, said: “As the world copes with the coronavirus pandemic, many countries have achieved control through great effort and cost. In our peer-reviewed letter we present data that paints an clear picture of the current state of the pandemic: only a small percentage of people have been infected, the infection fatality rate is higher than seasonal flu, and this terrible disease is unlikely to go away on its own. Claims to the contrary, suggesting that we have already reached herd immunity, can be firmly rejected by independent, credible data from around the world. In short, the pandemic is far from over.”
- The researchers reached their conclusions after looking at multiple data sources. They found that the cumulative mortality rate from C19 plateaued at very different levels in different countries, whereas with herd immunity this might be expected to be broadly the same. For example, there are large differences in mortality rates between Germany, the Netherlands and Italy, which all have good quality health care and testing capacity.
- Countries that went into lockdown early also experienced fewer deaths in subsequent weeks, according to the analysis, suggesting the differences in the timings and stringency of lockdowns and interventions explain the different C19 death rates in these countries. The authors argue this would not have been the case if epidemics had faded out due to herd immunity being reached.
Source: Declines in COVID-19 cases not due to herd immunity – NIHR Imperial Biomedical Research Centre
Note: A full copy of the study can be found at the Lancet here
2. How many needless C19 deaths were caused by delays in responding? Most of them
Opinions by Isaac Sebenius and James K. Sebenius
- More than 120,000 Americans have now perished from C19, surpassing the total number of U.S. dead during World War I. Had American leaders taken the decisive, early measures that several other nations took when they had exactly the same information the U.S. did, at exactly the same time in their experience of the novel coronavirus, how many of these C19 deaths could have been prevented?
- That isn’t a hypothetical question. And the answer that emerges from a direct comparison of the fatalities in and policies of the U.S. and other countries — South Korea, Australia, Germany, and Singapore — indicates that between 70% and 99% of the Americans who died from this pandemic might have been saved by measures demonstrated by others to have been feasible.
- At least three factors enable meaningful comparisons of these nations with the United States. First, we scaled up their population sizes and C19 deaths to match those of the U.S. Second, in each of these countries, roughly 80% or more of the population lives in urbanized, transmission-prone areas, similar to the U.S. Third, the pandemic took root earlier in these other countries than here, as measured by the date of the 15th confirmed case in each, meaning that foreign leaders had to act with less information to guide their decisions than did U.S. leaders.
- To compare each country’s responses to the pandemic on a consistent basis, we turned to the work of an Oxford University team that has constructed a stringency index based on 13 policy responses (lockdowns, border closings, tests, etc.) to measure how strongly each country responded over time. The Oxford index shows that 14 days from the date of the 15th confirmed case in each country — a vital early window for action — the U.S. response to the outbreak lagged behind the others by miles. The U.S. stringency score of 5.7 at that point was 25% of Australia’s (23), 23% of Germany’s (25), 18% of Singapore’s (32), and only 15% of South Korea’s (38).
- Due to exponential viral spread, our delay in action was devastating. In the wake of the U.S. response, 117,858 Americans died in the four months following the first 15 confirmed cases. After an equivalent period, Germany suffered only 8,863 casualties. Scaling up the German population of 83.7 million to America’s 331 million, a U.S.-sized Germany would have suffered 35,049 C19 deaths. So if the U.S. had acted as effectively as Germany, 70% of U.S. coronavirus deaths might have been prevented.
- Seventy percent, though, is the most conservative estimate. Scaled-up versions of South Korea, Australia, and Singapore would have experienced 1,758, 1,324, and 1,358 deaths, respectively, in the four months after 15 cases were confirmed in each country. Had we handled the coronavirus as effectively as any of these three countries, roughly 99% of the 117,858 U.S. C19 deaths might have been averted.
- Our conclusions are strengthened by their consistency with the results from different methodologies. Two notable epidemiological projections, based on theoretical models of transmission and “idealized hypothetical assumptions,” have estimated that between 80% and 90% of American deaths could have been averted had lockdowns and social distancing begun two weeks earlier.
- For a more granular perspective, we compared the American response to the actions taken by South Korea. By the time South Korea experienced its 15th confirmed case on Feb. 2, it had spearheaded a massive public information campaign, mobilized private sector players to produce testing kits, and expedited regulatory approval for these newly developed tests. Within a week, tests were widely available. Within three weeks, schools and public spaces were closed, large gatherings had been banned, and 26,000 people had been tested.
- In contrast, President Trump consistently ignored confidential and public early warnings from experts and intelligence agencies prior to the 15th confirmed U.S. case on Feb. 14, then acted far more slowly and inconsistently than South Korea. The White House banned flights from China on Feb. 2 but later permitted more than 40,000 travelers from China to enter the U.S. From February through April, President Trump made dismissive and contradictory statements to which government agencies and the public paid close attention.
- Often taking cues from the president’s words, state by state measures were rolled out piecemeal. Florida and Georgia, for example, waited until April 3 to issue stay-at-home orders while South Carolina held off until April 7.
- Another crucial failure involved testing. Three weeks after the 15th C19 case had been confirmed in the U.S., only about 10,000 tests had been administered. By an equivalent point in its epidemic, South Korea had administered approximately 17 times more tests per capita than the U.S. had done. This testing fiasco crippled vital early contact tracing efforts when hot spots could have been contained.
- South Korea’s decisive actions during this critical early window produced a dramatic disparity. By mid-March, each of the two countries had suffered about 90 C19 deaths. But throughout April, while a total of 85 South Koreans died from the disease, an average of more than 85 Americans died per hour. This divergence only widened as time passed.
- Although federal, state, and local governments share responsibility for American health policy and implementation, ultimate accountability during a national crisis heavily rests on the occupant of the White House. At a minimum, the president, perhaps through a tough “testing czar,” should have empowered private companies, labs, and hospitals to augment public testing efforts — as South Korean policymakers did — and imported readily available tests from elsewhere if necessary. If there were shortages of testing components, the president should have immediately invoked the Defense Production Act rather than waiting for months to do so for this purpose. And when the CDC and the FDA fumbled early testing efforts, President Trump responded: “I don’t take responsibility at all.”
- The administration has advanced innumerable excuses and scapegoats for the vast U.S. death toll: China, the World Health Organization, the Centers for Disease Control and Prevention, former President Barack Obama, the media, and more. Yet other countries with the same information — or alleged misinformation — as the U.S. had at the time took earlier, decisive steps to quell the spread of the coronavirus. Relative to the United States, their actions dramatically cut their death tolls and, on average, South Korea, Australia, Germany, and Singapore are opening up their economies sooner and more safely than the U.S.
- Two recent studies published in Nature confirm the “astonishing effectiveness” of the type of government interventions we have discussed, especially when adopted early. Our analysis shows that with the same actions actually taken by other nations large and small, from East and West, the U.S. could have prevented 70% to 99% of its C19 deaths. This has been a needless tragedy.
[Note: The Editors of Coronavirus Update welcome a diverse set of opinions on the virus and related issues. In our opinion, this editorial is a classic case of “Monday Morning Quarterbacking.” First, the models/projections offered by the Imperial College and IHME have proven grossly inaccurate. Second, comparing the US’s lack of timely response to Asian countries who had previously experienced SARS and MERS is not a valid comparison. Third, studies of sewage and wastewater systems in Europe indicate the virus was present long before the first known case of C19. Finally, Germany’s population tends to have a high level of trust in its government institutions. The USA’s culture, belief in independence and lack of trust in our government institutions would have made closing down the country early next to impossible. In fact, President Trump received intense criticism for shutting down travel from China and Europe when he did.]
Source: A faster response could have prevented most US Covid-19 deaths
K. Pandemic Economy
1. 5 charts that track how the U.S. economy is recovering from coronavirus
- With states continuing to lift coronavirus restrictions, people across the U.S. have felt more comfortable traveling, taking transit, eating out and even moving to a new home.
- Improvement across the travel and restaurant industries, as well as the housing market, could signal that a broader economic recovery is on the horizon even though the pandemic is still ongoing.
- These five charts illustrate trends in key economic indicators that help track reopening progress in the U.S.
Direction requests
- Travelers are relying more on Apple Maps for help regarding public transportation, according to the latest data from the navigation app. Transit directions from the app are at almost half of what they were in January as more people return to work in urban centers like New York City and San Francisco. However, requests for walking and driving directions fell lower than what they were earlier in June.
Restaurant bookings
- Restaurant bookings are down more than 60% compared to last year, according to data from online reservation service OpenTable. Bookings were down 100% in part of March and all of April, as restaurants across the country could only offer pick-up and delivery instead of onsite dining. However, reservation bookings began to rise in May as states eased restrictions and enabled diners to eat out again.
Hotel occupancy
- Hotels are filling up more with an occupancy rate of about 42%, according to data from global hospitality research company STR. With more kids out of school and summer weather underway, families across the country may be looking forward to traveling. Norfolk/Virginia Beach, Virginia was the only major travel market to achieve above a 50% hotel occupancy rate, but was followed close behind by Phoenix, New York City and Tampa, Fla., according to STR.
Air travel
- The number of daily travelers going through airport security checkpoints is down around 80% compared to last year, according to data from the Transportation Security Administration. Passenger numbers have crept up steadily since they plummeted in March during the early stages of the coronavirus pandemic. The air travel industry is now waiting to see if passenger numbers make a bigger rebound during the busy summer season.
Home purchases
- Mortgage applications for buying a single-family home are now up 21% compared to last year as mortgage rates drop to record lows, according to data from the Mortgage Bankers Association. “Purchase applications increased to the highest level in over 11 years and for the ninth consecutive week,” said Joel Kan, associate vice president of economic and industry forecasting at MBA. “The housing market continues to experience the release of unrealized pent-up demand from earlier this spring, as well as a gradual improvement in consumer confidence.”
Source: Here are five charts that track how the US economy is recovering from coronavirus
L. Johns Hopkins COVID-19 Update
June 19, 2020
1. Cases & Trends
- The WHO C19 Situation Report for June 18 reports 8.24 million confirmed cases (181,232 new) and 445,535 deaths (5,245 new). This is the WHO’s 150th C19 Situation Report. The WHO reported 8 million global cases on June 17. Overall, the global daily incidence continues to increase, and the pandemic appears as though it continues to accelerate.
Chile
- This daily incidence is the highest reported by the WHO to date, surpassing the previous high by nearly 39,000 cases. A significant driver of the increased incidence is Chile, which reported a large one-day spike of 36,179 new cases. Archived versions of the Chilean C19 website are not available for June 16, but between June 15 and June 17, Chile’s cumulative confirmed C19 incidence jumped from 179,436 cases to 220,628. The Chilean Ministry of Health stated that it identified nearly 30,000 C19 cases that were not previously included in the national surveillance data and reported them on June 16. Several news media reports cite the total as 31,412 cases. Other than June 16, Chile is reporting approximately 5-7,000 new cases per day and steadily increasing. Chile is currently reporting 225,103 cumulative cases (4,475 new).
India, Pakistan& Bangladesh
- India reported 13,586 new cases, setting a new high for daily incidence for the second consecutive day. India’s C19 epidemic has accelerated rapidly over the past several weeks, with the daily incidence doubling since May 28. India is currently #4 in terms of daily incidence. We are tracking a 3-day average, which is still affected by Chile’s recent spike in incidence, and we expect India to resume the #3 position. Pakistan reported 4,944 new cases. This is Pakistan’s tenth highest daily total to date, substantially fewer cases than its recent peak of 6,825 new cases on June 13. Pakistan remains #6 globally in terms of daily incidence. Since reporting 4,008 new cases on June 16, Bangladesh has reported 2 consecutive days of decreasing daily incidence, down to 3,243 new cases yesterday—still Bangladesh’s fifth highest daily total. Bangladesh is currently #9 globally in terms of daily incidence.
Russia
- Russia reported fewer than 8,000 new cases for the first time since early May. Russia is currently #5 in terms of daily incidence, but we expect it to return to #4 when Chile’s 3-day average returns to normal.
Brazil
- Brazil reported 22,765 new cases. Brazil’s incidence reporting pattern typically includes 4-5 days of higher incidence interspersed with 1-2 days of lower incidence; however, Brazil only reported 2 days of elevated incidence this week before decreasing in its most recent update. That being said, the decreased value is still greater than in previous weeks, so it remains to be seen whether this is indicative of any longer-term trend. Brazil remains #1 globally in terms of daily incidence.
Central & South America
- Broadly, the Central and South American regions are still a major C19 hotspot, representing 5 of the top 13 countries globally in terms of daily incidence—including Chile (currently #3, but likely to return to #5), Mexico (#7), Peru (#10), and Colombia (#13)—and 4 of the top 11 in terms of per capita daily incidence—Chile (currently #1, but likely to return to #2-3), Panama (#6), Brazil (#7), and Peru (#11).
Iran
- Iran reported 2,615 new cases, bringing its national total to 200,262 cumulative cases. While still lower than both the peak last week and its first peak in late March, Iran’s current daily incidence remains elevated. Iran is currently #12 globally in terms of daily incidence.
Eastern Mediterranean Region
- Overall, the Eastern Mediterranean Region remains an emerging hotspot, representing 5 of the top 11 countries in terms of per capita incidence—Qatar (currently #2, but likely to return to #1), Bahrain (#3), Oman (#5), Saudi Arabia (#8), and Kuwait (#9). Additionally, nearby Armenia is #4. In addition to Iran, Saudi Arabia is currently #8 globally in terms of total daily incidence, and Qatar is #19, despite ranking only #139 by population.
United States
- The US CDC reported 2.16 million total cases (22,834 new) and 117,632 deaths (754 new). In total, 18 states (increase of 2) and New York City reported more than 40,000 total cases, including New York City with more than 200,000; California, New Jersey, and New York state with more than 150,000; and Illinois with more than 125,000.
- Following an overall decrease in daily incidence from mid-April through the end of May, the United States’ national C19 incidence appears to be increasing since early June, several weeks after states began to relax social distancing measures.
- The New York Times, ProPublica, Johns Hopkins University, and others continue to track state- and local-level C19 incidence in a variety of forms. A number of states began to relax social distancing measures at the end of April/early May. Increased social interaction as well as mass gatherings associated with the Memorial Day holiday weekend and large-scale protests against racial and social injustice could potentially contribute to increased community transmission. We will continue monitoring these trends over the coming weeks.
- Numerous US states continue to report concerning C19 trends. The New York Times analysis indicates that 20 states are reporting significant increases in C19 incidence, based on a 7-day average. Among these states, 12 appear to be reporting record daily incidence over the past several days. Texas reported its highest daily incidence and C19 hospitalizations yesterday as well as its second highest test positivity since April. Multiple hospitals in Florida are currently reporting that all of their intensive care unit (ICU) beds are occupied. According to data published by the Florida Agency for Health Care Administration (AHCA), 9 hospitals with a capacity of at least 25 ICU beds report no availability. Additionally, numerous smaller hospitals are also reporting zero available ICU beds, including 2 in Palm Beach, one of Florida’s current C19 hotspots. Arkansas and North Carolina continue to report increasing C19 hospitalizations. Notably, Arkansas is reporting nearly 4 times the number of hospitalized C19 patients as it was in mid-May and more than 7 times the number of active community cases.
- The Johns Hopkins CSSE dashboard reported 2.20 million US cases and 118,695 deaths as of 12:30pm on June 19.
2. RNA Vaccine Development
- The United Kingdom announced that a Phase 1 clinical trial is scheduled to begin for a vaccine developed by Imperial College London. The vaccine utilizes self-amplifying RNA technology, and it will be administered to 300 health participants (2 doses). The vaccine received £41 million (US$51 million) in funding from the UK government and another £5 million (US$6 million) from various philanthropies and the public. The researchers believe the vaccine will be easier and less expensive to produce than traditional vaccines, and efforts are ongoing to establish a funding mechanism to make the vaccine widely available at a low cost. Imperial College is partnering with Morningside Ventures, a Hong Kong-based investment firm, to form a company to coordinate global manufacturing capacity and distribution.
- Multiple SARS-CoV-2 vaccine candidates are utilizing self-amplifying RNA; however, there are no existing approved vaccines that use this technology. This type of platform has also be used in candidate vaccines against Ebolavirus and cancer therapy. Self-amplifying RNA vaccines have been demonstrated to produce immunogenic responses in animal models that are comparable to mRNA vaccines, with the benefit of requiring smaller doses. In one recent study (preprint), researchers at Imperial College found that their vaccine candidate produced a robust immune response in mice following 2 doses of the vaccine, which will hopefully translate to promising results in future in human trials. While self-amplifying RNA vaccines may offer a range of benefits, a number of barriers remain, including challenges with vaccine stability and delivery methods to ensure successful uptake.
3. Remdesivir Clinical Trial
- Gilead Sciences announced that it will soon begin enrollment of an open-label, single-arm Phase 2/3 clinical trial to investigate the use of remdesivir as a treatment for pediatric C19 patients. The trial is designed to involve approximately 50 pediatric patients with moderate-to-severe C19, including newborns, across 30 sites in the United States and Europe, and it is scheduled to be completed by December 2020. Remdesivir was previously available to pediatric patients via compassionate use and Emergency Use Authorization (EUA), but a clinical trial will provide valuable data to evaluate its efficacy and safety in pediatric patients.
4. Vaccine Development & Allocation
- The European Commission is reportedly negotiating with pharmaceutical company Johnson & Johnson to reserve doses of its SARS-CoV-2 vaccine candidate. This development follows the announcement of a mandate from 27 EU governments to use €2 billion (US$2.3 billion) to arrange access to vaccine supply from multiple vaccine developers. Germany, Italy, and the Netherlands recently secured approximately 400 million doses of the AstraZeneca candidate vaccine, which could be allocated across EU member states. The United States made a similar arrangement with the company.
- Arrangements between pharmaceutical companies and governments of high-income countries have raised concerns that low-income countries may not be able to access sufficient doses of vaccines as they become available. While international organizations and stakeholders—including the WHO, Médecins Sans Frontières (MSF), and Gavi—have advocated for and promoted equitable allocation of the SARS-CoV-2 vaccine, there is a lack of legally enforceable mechanisms and frameworks to enforce it, particularly for situations in which vaccine development efforts have received funding from national governments. An editorial published in Nature called for pooling relevant data and proprietary information necessary to advance vaccine development and production, similar to open-source software, in order to enable more companies and countries to contribute to these efforts. This concept has been met with opposition from vaccine manufacturers, who are concerned about the maintaining the value of their intellectual property, and high-income country governments that have invested in vaccine research and development.
5. Convalescent Serum Antibodies
- A recent study published in Nature evaluated the neutralizing capacity of convalescent serum collected from recovered C19 patients. The study generally found low levels of neutralizing activity present in the specimens. The researchers did find that all of the specimens possessed at least a small volume of potent antibodies specific to the receptor binding domain (RBD) of SARS-CoV-2. The ability of these potent neutralizing antibodies to target the RBD portion of the virus has implications for vaccine development. If a vaccine could be designed to elicit an immune response that produces many of these RBD-specific antibodies, then such a vaccine could induce sufficient protection against infection. Additional research is required to better characterize the immune response to SARS-CoV-2 infection and the potential role of convalescent serum as a potential treatment or prophylaxis.
- While the benefits of convalescent serum are still being studied, the Mayo Clinic (Minnesota, US) recently published (pre-proof) a study that found serum transfusion to be a safe procedure for patients with minimal side effects. This study evaluated serious adverse events reported among 20,000 patients who received convalescent serum transfusion between April 3 and June 2, 2020. Fewer than 1% of all transfusions resulted in serious adverse events.
6. WHO End Hydroxychloroquine Trial
- Following the US FDA decision to revoke the EUA for hydroxychloroquine, the WHO announced that it is terminating the hydroxychloroquine arm of its Solidarity trial. The WHO based its decision on data from several clinical trials, including the Solidarity trial and trials conducted in the United Kingdom and France, as well as a review of other available evidence. Overall, the data did not demonstrate reduced mortality among C19 patients treated with hydroxychloroquine compared to the existing standard of care. The WHO update does not reference an increased risk of serious adverse effects that has been documented in other studies.
7. Proning
- In a small cohort study, conducted at Columbia University (New York, US) and published in The Journal of the American Medical Association: Internal Medicine (JAMA Internal Medicine), researchers found that placing non-intubated C19 patients with severe respiratory failure in the prone position (ie, lying on their stomach) was associated with improved saturated oxygen levels. The study included 25 C19 patients in the intermediate care unit, who were asked to place themselves in the prone position for as long as tolerable, up to 24 hours per day. Participants were able to move themselves into other positions; in fact, the ability to move in and out of the prone position without assistance was part of the inclusion criteria. After 1 hour in the prone position, saturated oxygen levels increased between 1% and 34% over their baseline assessment across all 25 participants, with a median improvement of 7%. This study is limited by the small sample size and lack of a control group; however, these preliminary findings are a positive indicator of the potential clinical benefits of proning non-intubated C19 patients.
8. Arizona Social Distancing
- Following a recent surge in reported C19 incidence in Arizona—along with increases in C19 hospitalizations, test positivity, and other indicators—Governor Doug Ducey issued an executive order to enhance the state’s response and strengthen social distancing measures. Arizona aims to strengthen testing and contact tracing capacity, including mobilizing the Arizona National Guard. Arizona also published specific requirements for restaurants and other businesses to implement additional protective measures, including ensuring appropriate physical distancing (eg, 6-foot separation), mandating symptom monitoring and mask use for employees, and limiting groups or gatherings to no more than 10 people. The new guidance for restaurants and other businesses provides more detailed instruction than previous versions, including some new requirements. With respect to mask use, restaurant employees who interact with customers are now required to wear masks, and other businesses are directed to require employees to wear masks “when possible.” Previously, guidance for some businesses, such as retail stores, did not mention mask use at all.
- Governor Ducey’s previous executive order included a provision that prohibited local governments from implementing any measures that conflicted with or were more restrictive than those mandated by the state. Notably, the new executive order permits local governments to implement their own policies or requirements regarding mask use based on their local situation. Numerous mayors across Arizona coordinated to call on Governor Ducey to allow more flexibility and authority at the local level to address C19 risk, and several local governments have reportedly already indicated that they intend to mandate mask use to mitigate transmission risk in their communities. Arizona is one of a number of states reporting increased C19 incidence over the past several weeks, and it is among the first to implement additional restrictions in response to increased community transmission.
9. California Mandates Make Use Statewide
- California updated its C19 policies to mandate mask use statewide for environments in which it may not be possible to maintain proper physical distancing (e.g., 6-foot separation). The new guidance states that masks must be worn in places such as indoor public spaces (or waiting in line to enter), healthcare settings, public transportation or ride-sharing vehicles (drivers and passengers), workplaces where there is interaction with the public, food preparation areas, and other public spaces where it is not feasible to maintain physical distancing. California includes exceptions for children aged 2 years and younger, those with medical conditions that preclude them from safely wearing a mask, communicating with someone who reads lips, eating and drinking, and outdoor recreation where proper physical distancing can be maintained.
10. UK Risk Level 3
- The UK Joint Biosecurity Centre recommended that the UK C19 alert level be lowered from Level 4 to Level 3, and the Chief Medical Officers for England, Northern Ireland, Scotland, and Wales concurred. This signals that the UK epidemic is no longer exhibiting high transmission or exponential growth. It is unclear at this point how the lower alert level will translate to changes in the UK C19 response. When the system was unveiled on May 11, Alert Level 4 corresponded to maintaining the existing social distancing restrictions; however, the United Kingdom eased some restrictions earlier in June, while still at Alert Level 4. The United Kingdom reported 1,346 new cases, bringing its total to 301,815 cumulative confirmed cases, and it has reported steadily decreasing.
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