Recent Developments & Information
June 5, 2020
“Only when mobility increases more than halfway back from full-lockdown levels to pre-lockdown levels is there a risk of … a second wave.”David Mackie, JPM economist
“The percentage of the population susceptible to the coronavirus was never 100%, and was at most 50% and probably more like only 20% of the population.”Professor Karl Friston [Note: We’ll have more on this in our next Update]
Index Of Featured Stories & Links
Note: All of stories listed below are included in this Update, but we have included links to the stories upfront so that you can quickly jump to a story if you want.
- Potential Treatments
- A drug that cools the body’s reaction to C19 appears to save lives
- Famotidine (Pepcid AC) May Curb C19 Symptoms – Effects Felt Within 1–2 Days (!)
- New Scientific Findings
- Some people may have an immunological ‘head start’ against the virus, even if they’ve never been exposed
- Genes May Leave Some People More Vulnerable to Severe C19
- A Randomized Trial of Convalescent Plasma for C19 has Hopeful Signals
- Mortality Rate of Adults With Critical Illness From C19 Is Less Than Previously Reported
- Roche Test for Severe C19 Gets Emergency FDA Approval
- Children are not big spreaders of coronavirus
- Coronavirus vaccine developers expect ‘two-dose regimen’
- AstraZeneca doubles coronavirus vaccine production capacity
- Brazil To Be First To Test Oxford’s C19 Vaccine
- MIT engineers develop a system to get the most out of ventilators
- NASA Has Selected 8 US Manufacturers to Make New C19 Ventilator
- The Road Back?
- Dine-in guidelines are ‘not sustainable’ for casual restaurants
- Projections & Our (Possible) Future
- Social bubbles may be the best way to emerge from lockdown
- You can access all of the updates on our website at https://dailyC19post.com/ and on Facebook at https://www.facebook.com/groups/2467516816834782/group_quality/. Please share the website and Facebook addresses with anyone you believe might be interested in the updates. Also, some have asked me to attach a copy of the update to each email, so I will do that going forward.
- We are happy to add anyone to the distribution list – just let me know. And, for those of you that are on social media, feel free to forward or post any or all of our updates or recommendations. Also, please forward to me any information than you believe should be included in any update, including any precautions that you recommend. Comments and suggestions are always welcome.
- 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. Our World As Seen Through Headlines
(In No Particular Order)
- NYC reports no new coronavirus deaths for first time since mid-March
- Brazil passes Italy to claim world’s third-worst death toll
- NY to allow drive-in, drive thru graduations
- Italy sees more good numbers
- Pakistan reports record jump
- NYC won’t allow outdoor dining until next month
- Florida reports most new cases since April for 2nd straight day
- Global cases top 6.7 million
- Deaths top 485,000
- Hong Kong sees another alarming cluster
- China allows foreign airlines to apply to return to service
- Russia, Mexico, Brazil all see alarming jump in cases, deaths
- Experts say Russia likely underestimating deaths in St. Petersburg by considerable margin
- Backlash to the hydroxychloroquine backlash intensifies
- Researchers Retract Botched Anti- Hydroxychloroquine Study Which Was Used To Attack Trump
- Chemicals used by police amid protests may spread COVID-19: CDC director
- Navy carrier sidelined by coronavirus back operating in Pacific
- Tennessee must allow vote by mail for everyone due to coronavirus, judge says
- Pittsburgh hospital officials say coronavirus infections are declining
- Alabama, Oklahoma State football players test positive for coronavirus
- Authors retract study claiming hydroxychloroquine had fatal side effects
- Robot that can safely swab for coronavirus developed by scientists in Denmark
- Gretchen Whitmer Violates Own Social Distancing Order During Protest
- Mexico Continues to Break Daily Coronavirus Death Record
- Gilead says drug helped moderately ill coronavirus patients
- Epidemic of wipes and masks plague sewers, storm drains
- NYC restaurants can have outdoor seating, open streets in Phase 2
- Sweden urges protesters to take it online during pandemic
- Barcelona locals reclaim city from tourists during pandemic
- Amazon workers sue over lax workplace policies in coronavirus crisis
- Doctors in Spain are wheeling recovering coronavirus patients to the beach
- Lion Air stops all service after passengers fail to follow coronavirus regulations
- After lockdown, Australians seek to learn survival skills in the bush
- Hundreds of NYC coronavirus victims buried in mass graves
- Spike in coronavirus in Israel’s capital spreads nationwide
- As coronavirus deaths surge in Brazil, calls for Bolsonaro’s impeachment intensify
- France to transform surplus wine into hand sanitizer
- New York Gov. Cuomo says state will open coronavirus testing to all protesters
- NYC Unveils Outdoor Dining Plan as Confirmed Tri-State Deaths Top 40,000
- NYC on track for Phase II Reopening on Monday if it isn’t burned to the ground by then
- Finland Reaches COVID-19 Milestone, Records No New Cases
- World Health Organization resumes coronavirus trial on malaria drug hydroxychloroquine after examining safety concerns
- No new COVID-19 cases from Lake of the Ozarks crowds, Missouri health director says
- Has Sweden’s COVID-19 Strategy Backfired?
- Architect of Sweden’s no-lockdown strategy says he has no regrets, and doesn’t plan to change approach
- NYC Finance Jobs Won’t Recover Until 2026, Dashing Hopes Of V-Shaped Recovery
- COVID-19 Triggers Transformation Into A New Economy
- Lockdowns “Maximize Economic Pain For Minimal Health Gains”
- Mass Mink Cull Ordered on Dutch Farms to Stem Coronavirus Spread
- Robots And Social Distancing Will Revolutionize Restaurants In Post-COVID World
- The NBA is coming back
- Plastic surgeon in Florida offering drive-thru Botox to quarantined residents
B. Key Numbers & Trends
Note: Unless otherwise noted, all numbers in this Update are as of 5/31 and changes are since the prior day. Unless otherwise specified, all cases/deaths are confirmed cases/deaths that have been reported. Please note that the reporting of cases/deaths for a state/country may be delayed (which often occurs over weekends and holidays), and the number of cases/deaths for a state/country can be revised, which can result in some unusual short-term changes in numbers.
1. Cases & Tests
- Total Cases = 6,692,686 (+2.0%)
- New Cases = 129,991 (+46,473)
- New Cases (7 day average) = 113,111 (+1.8%) (+1,955)
- Total Cases = 1,924,051 (+1.2%)
- New Cases = 22,268 (+1,690)
- Growth Rate of New Cases (7 day average) = +0.1%
- New Cases (7 day average) = 22,227 (-0.3%) (-56)
- Total Number of Tests = 19,568,069 (+471,398)
- Percentage of positive test (7 day average) = 4.9%
- The number of new cases has stabilized over the last 7 days with an average growth rate of approx. 0.1%, which is a positive trend, particularly in light of large number of tests
- The number of tests is growing at a much faster rate than growth in number of new cases, which indicates that the number of new cases reflects, in large part, improved detection from more tests rather than increased spread of the virus
- 7 day average percentage of positive tests continues to decline, which is also a positive trend and perhaps the best indicator that the virus is not spreading on a large scale (although there may be hotspots where the virus is spreading significantly)
- Worldwide Deaths
- Total Deaths = 392,286 (+1.4%)
- New Deaths = 5,498 (+569)
- New Deaths (7 day average) = 4,391 (+3.0%) (+127)
- US Deaths
- Total Deaths = 110,173 (+0.9%)
- New Deaths = 1,031 (-52)
- Change in Number of Deaths (7 day average) = +0.9%
- New Deaths (7 day average) = 978 (-2.7%) (-27)
3. The number of confirmed worldwide cases is growing faster than ever as new hot spots emerge
- The pandemic is ebbing in some of the countries that were hit hard early on, but the number of new cases is growing faster than ever worldwide, with more than 100,000 reported each day.
- Twice as many countries have reported a rise in new cases over the past two weeks as have reported declines, according to a New York Times database. On May 30, more new cases were reported in a single day worldwide than ever before: 134,064. The increase has been driven by emerging hot spots in Latin America, Africa, Asia and the Middle East.
- Over all, there have been more than 6.3 million reported cases worldwide and more than 380,000 known deaths. More than a quarter of all known deaths have been in the United States. But the geography of the pandemic is changing quickly.
- The increases in some countries can be attributed to improved testing programs. But in many places, it appears that the virus has only now arrived with a wide scope and fatal force. Here is a look at some of the countries where the number of new cases has been doubling every two to three weeks.
The death toll in Brazil, Latin America’s largest country, passed 30,000 on Tuesday, when officials reported 1,262 deaths, which was the nation’s highest one-day total. Brazil now has more than half a million known cases, second only to the United States. [Note: Brazil’s deaths on 6/4 increased to 1,492, the highest number of deaths in the world.]
Peru has more than 170,000 confirmed cases, despite taking the virus seriously early on. The president, Martín Vizcarra, ordered one of the first national lockdowns in South America. Though the official virus death toll stands at around 5,000, Peru had 14,000 more deaths than usual in May, suggesting that a growing number of people are dying at home as hospitals struggle to handle a flood of cases.
The pandemic provoked an exodus from Lima, the capital, as people unable to work fled by bus, and even by foot, to family farms. It is widely expected that the number of new cases and of deaths will continue to rise in coming weeks as winter nears and the economy slowly reopens.
For months, Egypt, the Arab world’s most populous country, seemed to avoid the worst of the pandemic. In early March, Egypt confirmed 45 cases on a Nile tour boat in the area, among both crew and passengers. But recently the number of cases there has been rising significantly, reaching 27,536 on Tuesday.
With more than 35,000 confirmed infections, the most in Africa, South Africa still has a growing number of new cases, despite enacting a strict lockdown in March that included a ban on the sale of tobacco and alcohol. The prohibition was lifted this month even though the total number of cases continued to rise.
Bangladesh now has 55,000 known cases. Its troubles were compounded last month by Cyclone Amphan, a deadly storm that tore through communities under lockdown. And this week, the country reported its first death from C19 in a refugee camp: A 71-year-old Rohingya man who died while receiving treatment in an isolation center.
[Note: The number of cases worldwide exceeded 100,000 for the first time on May 28, and has been in excess of 100,000 cases every day since then but one day (June 4). So, the number of daily cases is steadily increasing as it has since the beginning of the pandemic. However, it is inaccurate to say that the number of new cases is growing faster than ever. The number of new cases has been growing on average around 2% per day for a while, so the growth rate does not appear to be accelerating (and, in fact, the current growth rate is less than mid-April, when the growth rate was over 4% per day). At 2% per day, the number of new cases will double every 35 days.]
Source: NY Times
C. Potential Treatments
1. A drug that cools the body’s reaction to C19 appears to save lives
- In an advance toward conquering C19, doctors in Michigan say an antibody drug may sharply cut the chance patients on a ventilator will die.
- The problem: The pandemic viral disease is infecting millions, and for those who end up on a ventilator in an ICU, the odds are grim. More than half are dying.
- The drug: Doctors at the University of Michigan set out to control the haywire immune reaction that pushes some C19 patients into a death spiral. To do it, they gave 78 patients on ventilators the drug tocilizumab, which blocks IL-6, a molecule in the body that sets off a reaction to an infection. (The drug is sold by Roche under the trade name Actemra.)
- The result: The doctors say in a preprint that patients who got the drug were 45% less likely to die than those who didn’t. But there’s a big caveat, which is that the doctors knew which patients got the drug and which didn’t. Their picks for the drug-taking group could have been biased— people more likely to improve anyway, for example—so further studies are needed.
- Emerging cocktail: In late May, Roche said it would start a trial to combine its IL-6 blocker with remdesivir, an antiviral drug with modest benefits that got emergency approval in the US for treating C19. That drug is meant to block the virus from replicating.
- By combining the two drugs, doctors may be closing in on a cocktail able to cut the death rate from the virus, a step that would help society return to normal.
2. Famotidine (Pepcid AC) May Curb C19 Symptoms – Effects Felt Within 1–2 Days
- A widely available and inexpensive drug that is used to ease the symptoms of indigestion may prove a worthy contender for treating C19 infection in those whose disease doesn’t require admission to hospital, suggest the findings of a small case series, published online in the journal Gut.
- The effects were felt within 24 to 48 hours of taking famotidine, and a rigorous clinical trial is now warranted to see if the drug could be an effective treatment for C19, say the researchers.
- Famotidine (Pepcid AC) belongs to a class of drugs known as histamine-2 receptor antagonists, which reduce the amount of stomach acid produced. Famotidine can be taken in doses of 20-160 mg, up to four times a day, for the treatment of acid reflux and heartburn.
- The researchers report on 10 people (6 men; 4 women) who developed C19 infection, all of whom happened to have been taking famotidine during their illness.
- The severity of five cardinal symptoms — cough; shortness of breath; fatigue; headache and loss of taste/smell as well as general unwellness — was measured using a version of a 4-point scale normally applied to assess the severity of cancer symptoms (ECOG PS).
- Seven of the patients tested positive for C19, using a swab test; two had antibodies to the infection; and one patient wasn’t tested but was diagnosed with the infection by a doctor.
- Their ages ranged from 23 to 71 and they had a diverse range of ethnic backgrounds and known risk factors for C19 severity, including high blood pressure and obesity.
- All started taking famotidine when they were feeling very poorly with C19, the symptoms of which had been going on from 2 up to 26 days at that point.
- The most frequently used dose was 80 mg taken three times a day, with the average treatment period lasting 11 days, but ranging from 5 to 21 days.
- All 10 patients said that symptoms quickly improved within 24-48 hours of starting famotidine and had mostly cleared up after 14 days.
- Improvement was evident across all symptom categories assessed, but respiratory symptoms, such as cough and shortness of breath, improved more rapidly than systemic symptoms, such as fatigue.
- Seven of the patients didn’t experience any side effects while on famotidine, and in the three who did, these were mild, and all but temporary forgetfulness were known side effects associated with taking the drug.
- While promising, the researchers point out that the findings might have been affected by ‘the placebo effect,’ and/or hazy recall, added to which the number of case study participants was small.
- “Our case series suggests, but does not establish, a benefit from famotidine treatment in outpatients with C19,” they caution. And it’s not clear how famotidine might work: if it might incapacitate the virus in some way or alter a person’s immune response to it.
- “Clinically, we unreservedly share the opinion that well designed and informative studies of efficacy are required to evaluate candidate medications for C19 as for other diseases,” they emphasize.
- Nevertheless, they suggest their findings warrant further more detailed study, adding that a clinical trial, testing the combination of famotidine with the antimalarial drug hydroxychloroquine in patients admitted to hospital with C19, is already underway.
- “An outpatient study of oral famotidine that investigates efficacy for symptom control, viral burden and disease outcome and assesses the effects of medication use on long term immunity should be considered to establish if famotidine may be of use in controlling C19 in individual patients while also reducing the risk of coronavirus transmission,” they conclude.
D. New Scientific Findings & Research
1. Some people may have an immunological ‘head start’ against the virus, even if they’ve never been exposed
- Some people’s immune systems may have a head start in fighting the coronavirus, recent research suggested.
- A study published last month in the journal Cell showed that some people who have never been exposed to the coronavirus have helper T cells that are capable of recognizing and responding to it.
- The likeliest explanation for the surprising finding, according to the researchers, is a phenomenon called cross-reactivity: when helper T cells developed in response to another virus react to a similar but previously unknown pathogen.
- In this case, those T cells may be left over from people’s previous exposure to a different coronavirus — likely one of the four that cause common colds.
- “You’re starting with a little bit of an advantage — a head start in the arms race between the virus that wants to reproduce and the immune system wanting to eliminate it,” Alessandro Sette, one of the study’s coauthors, told Business Insider.
- He added that cross-reactive helper T cells could “help generate a faster, stronger immune response.”
- For its study, Sette’s team examined the immune systems of 20 people who got the coronavirus and recovered, as well as blood samples from 20 people that had been collected between 2015 and 2018 (meaning there was no chance those people had been exposed to the new coronavirus).
- Among the 20 confirmed C19 patients, the researchers found, every person had both the white blood cells specifically engineered to fight the virus and the resulting antibodies.
- “The data are suggestive that the average person makes a good immune response and may have immunity for some time,” Shane Crotty, another coauthor of the study, told Business Insider.
- He added that this finding probably meant that “the many vaccines people are trying to make should be able to replicate natural immunity.”
- Among the 20 people whose blood samples were taken before the pandemic, 50% had a type of white blood cell called CD4+ — T cells that help the immune system create antibodies — that the researchers found to be capable of recognizing the coronavirus and prompting the immune system to fight back right away.
- More research is needed to know whether or to what degree this cross-reactivity influences the severity of a case.
- “It is too early to conclude that cross-reactivity with cold coronaviruses plays a role in the mild or severe clinical outcome of C19 or the degree of infection in the populations,” Maillère Bernard, a scientist at CEA/Université de Paris-Saclay in France who was not involved in the study, told Business Insider.
- “The immune memory is related to the event. If it’s a strong event, you’ll have a strong memory,” Sette added. “If you almost got run over by a truck, you’ll remember it, but you may not remember the color of the socks you wore yesterday because it’s not a big deal.”
- Yuan Tian, a scientist at the Fred Hutch Institute in Seattle who was not involved in the research, told Business Insider that to learn more about how T cells relate to immunity, “it’d be interesting to study people with severe disease and compare the T-cell response between them and those with mild disease.”
- That’s next on the docket, according to Crotty.
- “We’re looking to identify T-cell response in the critically hospitalized,” he said. “It’s being done as we speak.”
2. Genes May Leave Some People More Vulnerable to Severe C19
Geneticists have turned up intriguing links between DNA and the disease. Patients with Type A blood, for example, seem to be at greater risk
- Why do some people infected with the coronavirus suffer only mild symptoms, while others become deathly ill?
- Geneticists have been scouring our DNA for clues. Now, a study by European scientists is the first to document a strong statistical link between genetic variations and C19.
- Variations at two spots in the human genome are associated with an increased risk of respiratory failure in patients with C19, the researchers found. One of these spots includes the gene that determines blood types.
- Having Type A blood was linked to a 50% increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study.
- The study was equally striking for the genes that failed to turn up. The coronavirus attaches to a protein called ACE2 on the surface of human cells in order to enter them, for example. But genetic variants in ACE2 did not appear to make a difference in the risk of severe C19.
- The findings suggest that relatively unexplored factors may be playing a large role who develops life-threatening C19. “There are new kids on the block now,” said Andre Franke, a molecular geneticist at the University of Kiel in Germany and a co-author of the new study, which is currently going through peer review.
- Scientists have already determined that factors like age and underlying disease put people at extra risk of developing a severe case of C19. But geneticists are hoping that a DNA test might help identify patients who will need aggressive treatment.
- Figuring out the reason that certain genes may raise the odds of severe disease could also lead to new targets for drug designers.
- As the pandemic gained momentum in February, Dr. Franke and his colleagues set up a collaboration with doctors in Spain and Italy who were struggling with a rising wave of C19.
- The doctors took blood samples from 1,610 patients who needed an oxygen supply or had to go on a ventilator. Dr. Franke and his colleagues extracted DNA from the samples and scanned it using a rapid technique called genotyping.
- The researchers did not sequence all three billion genetic letters in the genome of each patient. Instead, they looked at nine million letters. Then the researchers carried out the same genetic survey on 2,205 blood donors with no evidence of C19.
- The scientists were looking for spots in the genome, called loci, where an unusually high number of the severely ill patients shared the same variants, compared with those who were not ill.
- Two loci turned up. In one of these sites is the gene that determines our blood type. That gene directs production of a protein that places molecules on the surface of blood cells.
- It’s not the first time Type A blood has turned up as a possible risk. Chinese scientists who examined patient blood types also found that those with Type A were more likely to develop a serious case of C19.
- No one knows why. While Dr. Franke was comforted by the support from the Chinese study, he could only speculate how blood types might affect the disease. “That is haunting me, quite honestly,” he said.
- He also noted that the locus where the blood-type gene is situated also contains a stretch of DNA that acts as an on-off switch for a gene producing a protein that triggers strong immune responses.
- The coronavirus triggers an overreaction of the immune system in some people, leading to massive inflammation and lung damage — the so-called cytokine storm. It is theoretically possible that genetic variations influence that response.
- A second locus, on Chromosome 3, shows an even stronger link to C19, Dr. Franke and his colleagues found. But that spot is home to six genes, and it is not yet possible to say which of them influences the course of C19.
- One of those gene candidates encodes a protein known to interact with ACE2, the cellular receptor needed by the coronavirus to enter host cells. But another gene nearby encodes a potent immune-signaling molecule. It is possible that this immune gene also triggers an overreaction that leads to respiratory failure.
- Dr. Franke and his colleagues are part of an international effort called the C19 Host Genetics Initiative.
- A thousand researchers in 46 countries are collecting DNA samples from people with the disease. They are now beginning to post data on the initiative’s website.
- Andrea Ganna, a genetic epidemiologist at the University of Helsinki, said that initiative’s collected data were beginning to point to a single spot on Chromosome 3 as a potentially important player.
- It’s not common for genetic variants to emerge out of studies of so few people, said Jonathan Sebat, a geneticist at the University of California, San Diego, who was not involved in the new study.
- “We were all hoping optimistically this was one of those situations,” Dr. Sebat said.
- Previous attempts to find any genetic loci that varied significantly between sick people and healthy ones have failed. Dr. Sebat speculated that the new study succeeded because the researchers focused only on people who had respiratory failure and were clearly vulnerable to serious forms of C19.
- “They had the ideal cohort,” he said.
- New studies, such as the one Dr. Sebat is running in California, will allow scientists to see if the two loci really do matter as much as they seem to now.
- The geneticists may be able to zero in on exactly which gene in each locus affects the disease, he said. And researchers will most likely find many other genes with subtler influences on the course of C19.
Source: NY Times
3. A Randomized Trial of Convalescent Plasma for C19 has Hopeful Signals
- Convalescent plasma for the treatment of infectious diseases has been used since the early 20th century and was associated with reduced mortality during the 1918 influenza, 2003 SARS, and 2009 influenza H1N13 pandemics. However, most published studies of these diseases were case series and retrospective comparisons of treated and non-treated individuals.
- Consistent with this, several uncontrolled case series of convalescent plasma use in patients with coronavirus disease (2019) C19 have suggested a possible benefit. Given encouraging historical precedents and the absence of proven antiviral therapies, convalescent plasma therapy has been proposed as a treatment option for C19.
- The availability of clinical information generated from randomized clinical trials is therefore of substantial importance given that the world remains in the grip of the C19 epidemic and convalescent plasma is currently in use in many countries, including the US.
- In their article in JAMA, Li et al present findings from the first randomized clinical trial of convalescent plasma therapy for patients with C19 conducted in China. In contrast to most other reports of convalescent plasma use in past epidemics, this study is noteworthy in that it used a randomized trial design and well-characterized plasma units with a high titer of antibody to the coronavirus. It was an important accomplishment to conduct a carefully controlled trial during a pandemic with an entirely new highly contagious disease that stressed health systems in an unprecedented way.
- However, the authors report that because the C19 outbreak in China was being contained while the trial was ongoing and new cases were unavailable for enrollment, the trial was terminated before it reached its targeted original sample size of 200 patients; only 103 were enrolled (for whom randomization was stratified by disease severity). Consequently, the study was underpowered and many comparisons between the convalescent plasma group and the control group were not statistically significant.
- Convalescent plasma use in the study was associated with some clinical improvement in severely ill patients, but not in critically ill patients. Greater efficacy in less ill individuals is expected because antibody therapies generally work best when administered earlier in disease. Historically, antibody therapy was effective in reducing the mortality of pneumococcal pneumonia when instituted in the first 3 days of symptom onset.
- Consequently, it is not surprising that patients with C19 who had tachypnea and hypoxia might benefit more from convalescent plasma than those who required mechanical ventilation. However, any indication of possible benefit in the severely ill group is noteworthy because these individuals had advanced disease, which is not considered optimal for antibody therapy. Lack of efficacy among patients who were receiving mechanical ventilation, some with multiorgan failure, highlights that the pathologic process in these individuals is likely irreversible.
- The convalescent plasma used in the study had high titers of IgG to the coronavirus, which correlated with neutralizing activity. While neutralizing activity is considered to be the main determinant of convalescent plasma efficacy, other antibody functions may also mediate protection. Correlates of antibody efficacy should be investigated in future studies. As reported in case series from Wuhan,4,5 plasma-treated patients had large reductions in their serum viral loads and most were virus negative 3 days after infusion.
- This observation establishes that convalescent plasma has antiviral activity, which is important because it indicates that antibody administration mediates a clear biological effect. The precedent of antiviral drug use against HIV and hepatitis C shows that reductions in viral load translate into clinical improvement, and earlier therapy is more effective than later therapy when organ damage is already present.
- In this regard, antibody-mediated viral elimination removes damaging antigens, which may translate into reduced tissue damage and inflammation. Hence, the antiviral effect of C19 convalescent plasma suggests that its use earlier in the course of disease could have potentially important therapeutic activity, especially in less severely ill individuals.
- Significant concerns have been raised about the use of convalescent plasma in C19. These include transfusion-related lung injury and transfusion-related circulatory overload. In addition, there have been theoretical concerns that the administration of antibodies might aggravate disease through antibody-mediated enhancement of pro-inflammatory effects. The study reported only 2 adverse events among the 52 individuals who received convalescent plasma, each of whom responded to corticosteroid administration. The occurrence of one episode within 2 hours of plasma administration characterized by chills and rash suggests a transfusion reaction. However, the second episode occurred within 6 hours and its association with plasma infusion is less certain. Overall, the paucity of adverse effects is reassuring and reduces concerns about adverse effects from antibody administration.
- Although the observed differences in mortality rates and hospital discharge rates between the convalescent plasma group and the control group did not reach statistical significance, these data provide valuable information for the magnitude of effects that may be expected in convalescent plasma studies. For example, the observed overall mortality difference of 24% vs 15.7% provides actionable information for the design of future trials to help ensure they are adequately powered. This difference in mortality is smaller than mortality reductions associated with convalescent plasma reported in prior studies involving 1918 influenza, SARS, and 2009 influenza H1N1, which ranged from 50% to 70%. Hence, assuming the results of the study by Li are generalizable, the findings may be helpful in estimating effect sizes for future studies of convalescent plasma use in hospitalized patients with C19.
- In the study by Li, the median age of the patients with severe disease was 70 years, and the median time between symptom onset and randomization was 30 days. Promising results with convalescent plasma treatment in patients with SARS2 and influenza H1N13 were obtained among younger patients, and in the case of SARS, earlier in the disease. The importance of a possible treatment benefit in older persons, in whom mortality from C19 is markedly higher than in younger persons, cannot be overstated.
- In addition, the apparent improvement in the clinical status of the subgroup of less severely ill patients a month after the onset of symptoms suggests that the beneficial effects of antibodies in C19 may be measurable as an improvement in inflammatory markers and viral elimination before clinical improvement is observed. The prolonged course of C19 in patients who recover also should be considered in the design of future studies.
- However, the study by Li has several important limitations, which are acknowledged by the investigators. The early termination of the trial most likely resulted in an underpowered study, thereby precluding any definitive conclusions about the role and potential efficacy of convalescent plasma for patients with C19. In addition, the open-label design, the possibility of an element of subjectivity for the primary outcome, lack of a protocolized approach to standard therapy, and variability among study centers also must be considered when interpreting the study findings.
- Despite these limitations, by virtue of its randomized design, this study takes prior case studies one step further by helping to separate the effects of convalescent plasma from concurrently administered agents, such as corticosteroids and antiviral agents.
- The signal of potential benefit of convalescent plasma in the subgroup of patients with severe C19 disease (ie, those without life-threatening C19 disease) is similar to findings from a recent preliminary report of a clinical trial of remdesivir for C19. Like remdesivir, convalescent plasma administration was associated with clinical improvement without a statistically significant effect on mortality, with the important caveat that remdesivir was evaluated in a larger study (n = 1063 randomized patients), whereas the study by Li et al was terminated prematurely and underpowered. For both studies, the importance of clinical improvement as a primary end point became apparent as the trials progressed.
- The availability of both convalescent plasma and remdesivir means that physicians now have at least 2 therapeutic options for C19, which raises the question of combination therapy.
- Despite only a few studies of the efficacy of combination therapy with antiviral drugs and specific antibodies, there is evidence that these agents may work well in combination. Given that the mechanisms of action of antiviral drugs and neutralizing antibodies are distinct, they could be synergistic. Future trials should consider the efficacy of combination antiviral and antibody therapies.
- Read the Study here: Convalescent Plasma Therapy and Clinical Improvement in Severe and Life-threatening COVID-19
4. Mortality Rate of Adults With Critical Illness From C19 Is Less Than Previously Reported
- An online first study published in Critical Care Medicine indicates the actual mortality rate of adults with critical illness from C19 is less than what was previously reported.
- Compared to earlier reports of a 50% mortality rate, the study finds that the mortality rate of critically ill patients who required mechanical ventilation was only 35.7%. About 60% of patients observed in the study survived to hospital discharge.
- The study observed patients 18 years and older from six C19 designated intensive care units in three hospitals in Atlanta, Ga. from March to April 2020. The authors note that several considerations may have influenced the outcomes of the study including that all critically ill patients with C19 in the hospital network were admitted to pre-existing ICUs that had adequate staffing ratios and equipment.
- An accompanying online first editorial examines the role of mainstream and social media in creating the narrative that intubation and mechanical ventilation were “the cause of suboptimal outcomes” for critically ill C19 patients, without accounting for hospital staffing and equipment shortages.
1. Roche Test for Severe C19 Gets Emergency FDA Approval
- A Roche Holding AG test to detect C19 patients who are most at risk of an extreme immune reaction won emergency use clearance from the U.S. Food and Drug Administration.
- The blood test, called Elecsys IL-6, can within 18 minutes identify patients who carry the virus and who may develop respiratory distress and require intubation, Roche said Thursday.
- Some patients develop a severe inflammatory response called a cytokine storm, which can be deadly. The test attempts to pinpoint those most at-risk people early by measuring levels of interleukin 6 in the blood, a marker for acute inflammation. The protein acts as a messenger from some immune cells to rouse others against the infection.
- “Time is specifically critical,” said Thomas Schinecker, the head of Roche’s diagnostics unit. “The test could help physicians in the quick identification of severe inflammatory response.”
- Roche also makes one of the most accurate serology tests, which hunt for coronavirus antibodies in the blood to identify past infection. Both run on Roche’s laboratory analysis systems, which can handle as many as 300 tests an hour.
Source: Bloomberg Technology
1. Children are not big spreaders of coronavirus
- A study by the Netherlands’ National Institute for Health (RIVM) published on Wednesday concluded that children under the age of 12 play little role in transmitting the new coronavirus.
- The study in the country’s leading medical journal Nederlands Tijdschrift Voor Geneeskunde followed the progress of the disease in 54 families, including 227 people in all.
- Studies in other countries have previously found that children are less often infected by the virus and, once infected, less often become seriously ill.
- “Yes, children can become infected, but transmission takes place primarily between adults of similar age, and from adults to children,” the study said in its conclusion.
- “Transmission between children, or from children to adults, as is known in influenza, appears to be less common.”
- A possible weakness in the study is that the families studied may not have been representative of the wider Dutch population.
- Participants were chosen from families identified by positive tests from March 23-April 16, a period when only seriously ill people with suspected C19 cases and healthcare workers were being tested in the Netherlands.
1. Coronavirus vaccine developers expect ‘two-dose regimen’
- The coronavirus vaccine may not grant full immunity after just one dose, according to a new report.
- When a vaccine proves effective, there’s a good chance it will entail a two-dose series, USA Today reported. Shots may need to be administered one month apart, with a booster following several years later.
- As of June 2, the World Health Organization (WHO) listed 10 vaccine candidates under clinical evaluation, with 123 candidates in preclinical evaluation.
- Barry Bloom, immunologist and professor of public health at the Harvard T.H. Chan School of Public Health in Boston, told USA Today that almost all of the vaccine developers are considering two shots in their regimens.
- According to the outlet’s report, the first shot in the series would “prime the immune system” to help the body recognize the virus, followed by a second shot to “strengthen the immune response.” [NOTE: A two shot regimen would require up to 14 doses of the vaccines!]
- When vaccine candidates reach human clinical trials, more precise dosing will become clear, Dr. Kelly Moore, associate director of immunization education for the Immunization Action Coalition, told the outlet.
- After the first dose of a vaccine, the immune system develops antibodies and immune cells in about 14 days, says L.J. Tan, chief strategy officer with the Immunization Action Coalition and co-chair of the National Adult Immunization Summit and National Influenza Vaccine Summit.
- Tan estimated any C19 vaccine requiring two doses would likely be administered about a month or two apart.
- In addition, WHO officials said the coronavirus isn’t mutating to become more dangerous during a briefing on Wednesday. Since the SARS-CoV-2 is seemingly stable so far, initial vaccines could act as boosters later on to extend immunity, Bloom told the outlet.
- However, scientists aren’t sure how durable people’s immune response will be. For coronaviruses causing the common cold, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said immunity almost always lasts less than a year.
- “It may be completely different with this coronavirus, with SARS-CoV-2, it may be that they induce a response that’s quite durable,” Fauci told the editor of the Journal of the American Medical Association.
- A two-dose regimen in treating C19 across the country may demand more extensive coordination and record-keeping to ensure patients receive the full course of vaccination.
2. AstraZeneca doubles coronavirus vaccine production capacity
- British drugmaker AstraZeneca has doubled manufacturing capacity for its potential coronavirus vaccine to 2 billion doses in a handful of deals involving Microsoft billionaire Bill Gates that guarantee early supply to lower-income countries.
- The deals with epidemic response group CEPI and vaccine alliance GAVI are backed by the World Health Organization and aim to quell concerns that the company was committing all initial supplies of the vaccine to the developed world.
- It is unclear if vaccines will work against the coronavirus but dozens of companies are in the race to develop one, and AstraZeneca’s partnership with Oxford University is one of a handful to be backed so far by the US COVID task force.
- The White House last month secured 300 million of the first doses of the potential vaccine, named AZD1222, in a deal that also committed more than $1 billion in backing to testing and manufacturing. UK has booked another 100 million.
- Under Thursday’s deals, the company will supply 300 million doses, starting this year, to CEPI and GAVI as it aims at fair and equitable distribution of the vaccine, Chief Executive Pascal Soriot said.
- He said AstraZeneca had also agreed terms with Serum Institute of India, the world’s largest manufacturer of vaccines by volume, to supply one billion doses for low and middle-income countries.
- Part of the vaccine doses produced by Serum will be used in India, with the remainder allocated to GAVI, the company said on a call with journalists.
- That leaves AstraZeneca with 300 million doses in planned production capacity, which has yet to be earmarked for use.
- Experts predict a safe and effective vaccine could take 12 months to 18 months to develop.
- The vaccine, previously known as ChAdOx1 nCoV-19, was developed by the University of Oxford and licensed to AstraZeneca. Immunity to the new coronavirus is uncertain and so the use of vaccines is unclear.
- “You can’t spend your time wondering is it going to work. We have to commit. That’s what we do in the industry — we bet on something. We are completely committed to the vaccine program to deliver,” Soriot said.
3. Brazil To Be First To Test Oxford’s C19 Vaccine
- Hard hit Brazil will be the first nation to test the Oxford University vaccine for the coronavirus. Two-thousand volunteers working on the front lines against the virus will be chosen for the trial, which will begin in Sāo Paulo this month.
- Denis Mizne, executive director of the Lemann Foundation, the group that is financing the São Paulo trials, called it “an important milestone” for Brazil. The Foundation was funded and created by Jorge Paulo Lemann and his family. Lemann became a billionaire thanks to investments in Brazilian beer giant AmBev and Heinz through his private equity firm 3G Capital.
- Brazil has definitely seen its better days, so a successful trial run in fighting the disease would life everyone’s spirits. Brazil is on the cusp of surpassing the United States in terms of coronavirus cases after fits-and-starts in fighting the infection curve early on.
- The trial will be conducted in cahoots with Brazil’s Ministry of Health, a division of the executive branch that has gone through two health chiefs in less than a month due to disagreements with president Jair Bolsonaro. They are now on their third.
- The Lemann Foundation is funding the tests for half of the 2,000 test patients in São Paulo. All of the volunteers are health care workers and many of them were on the front lines and have been exposed to the virus.
- Those chosen for the study must be seronegative, meaning they have not contracted the disease before.
- As part of the Oxford trial’s design, participants will receive the vaccine and then continue being exposed to the virus normally in their day-to-day work.
- Brazil, the second most populous country in the Americas after the U.S., is said to be a key part of the global development plan to test the Oxford vaccine because of its current position on the infection curve.
- “The most important thing is to carry out this stage of the study now when the epidemiological curve is still rising and the results may be more decisive,” said Dr. Lily Yin Weckx, principal investigator of the study and coordinator of the program in Brazil.
1. MIT engineers develop a system to get the most out of ventilators
- The C19 pandemic triggered ventilator shortages in hospitals around the world as clinicians rushed to treat symptoms of acute respiratory distress syndrome.
- Many ventilators can support more than one patient at a time, but doing so comes with complications that have made this practice inadvisable. For instance, air supply cannot be suited to each patient’s unique needs.
- The dire situations that many hospitals have faced during the pandemic inspired a team of researchers and doctors at MIT and Brigham and Women’s Hospital to create a new system to customize air pressure and volume to more safely support two people on one ventilator.
- The iSAVE, or the individualized system for augmenting ventilator efficiency, is a circuit made out of medical-grade, readily available materials. A study on the system was recently published in Science Translational Medicine.
- This machine is not the standard of care, but can be a tool in the extraordinary circumstances of the current pandemic, said Giovanni Traverso, the study’s senior author and an assistant professor at MIT. “These kinds of solutions are ones that one might contemplate when there are no other options. … The way that we see it, [this] is a tool that at least adds to that conversation and consideration.”
- Richard Branson, editor-in-chief of the journal Respiratory Care and professor at the department of surgery at the University of Cincinnati, said that while the scientists did “a reasonable job” of making the idea of sharing ventilators safer, it still should be the last resort.
- There are problems that could arise with a system like this. For example, creating more connections increases the risk of one of them getting disconnected. Patients also need to be monitored more carefully, which increases the complexity of care at a time when clinicians are already overwhelmed.
- “Everybody who does it really sits back and goes, ‘Boy, I hope we never really have to do this,’” said Branson, who co-authored two recent studies exploring the idea of ventilator sharing.
- Shriya Srinivasan, lead author of the study and an MIT postdoctoral fellow, recognizes that iSAVE does have its limitations — patients still have to share some properties of the ventilator, and clinicians have to monitor them more closely.
- The group is now trying to get emergency use authorization from the Food and Drug Administration. It’s also working with nonprofits in other countries to see if the system could help with their patients. The researchers sent these partners kits with all the needed components, so they can test the system at their hospitals.
- After receiving more than 100 applications, NASA’s Jet Propulsion Laboratory in Southern California has selected eight U.S. manufacturers to make a new ventilator tailored for C19 patients.
- The prototype, which was created by JPL engineers in just 37 days, received an Emergency Use Authorization from the FDA on April 30.
- Called VITAL (Ventilator Intervention Technology Accessible Locally), the high-pressure ventilator was designed to use one-seventh the parts of a traditional ventilator, relying on parts already available in supply chains. It offers a simpler, more affordable option for treating critical patients while freeing up traditional ventilators for those with the most severe C19 symptoms. Its flexible design means it also can be modified for use in field hospitals.
- The Office of Technology Transfer and Corporate Partnerships at Caltech, which owns the patents and software for VITAL, is offering a free license for the device. Caltech manages JPL for NASA.
- “The VITAL team is very excited to see their technology licensed,” said Leon Alkalai, manager of the JPL Office of Strategic Partnerships and a member of the VITAL leadership team. “Our hope is to have this technology reach across the world and provide an additional source of solutions to deal with the on-going C19 crisis.”
- JPL now is evaluating international manufacturers from countries including Brazil, Mexico, India and Malaysia.
- VITAL was developed with input from doctors and medical device manufacturers. A prototype of the JPL device was successfully tested by the Human Simulation Lab in the Department of Anesthesiology, Perioperative and Pain Medicine at Mount Sinai on April 23.
- A modified design, which uses compressed air and can be deployed by a greater range of hospitals, was recently tested at the UCLA Simulation Center in Los Angeles. A high-fidelity lung simulator tested almost 20 different ventilator settings, representing a number of scenarios that could be seen in critically ill patients in an intensive care unit.
- “VITAL performed well in simulation testing with both precise and reproducible results,” said Dr. Tisha Wang, clinical chief of the UCLA Division of Pulmonary and Critical Care Medicine. “In addition, the setup and operation of the ventilator was quick and user-friendly.
- The UCLA team commends JPL for actively contributing to the C19 response and successfully addressing one of the key medical needs in the sickest group of patients.”
- The compressed-air design also has been submitted to the FDA for a ventilator Emergency Use Authorization and is currently under review.
J. The Road Back?
1. Dine-in guidelines are ‘not sustainable’ for casual restaurants
- Guidelines put in place to enforce social distancing inside restaurant dining rooms are “not sustainable” for casual establishments, according to Buckhead Life Restaurant Group president Niko Karatassos.
- Buckhead Diner and Corner Cafe will once again close their dining rooms until the guidelines issued by Georgia Gov. Brian Kemp are lifted. The guidelines, which were created by the Georgia Restaurant Association in concert with public health officials, are meant to combat the novel coronavirus pandemic and stop the spread of C19 while allowing restaurants to stay in business.
- Buckhead Diner and Corner Cafe, which are more casual and have average checks that are lower than other Buckhead Life concepts, do not generate enough revenue with limited occupancy, Karatassos said. They are able to serve only half of the tables that would normally be available.
- “We’ve been open for a little bit,” Karatassos told Atlanta Business Chronicle. “It’s just become evident that until those guidelines are lifted, it doesn’t make sense to be losing money every day.”
- “The rent is 100%, the utilities are 100% and the seating is 50%.”
- Buckhead Life’s Bistro Niko, which resumed dine-in service in May, is now temporarily closed after sustaining damage during the local protests of George Floyd’s death. Kyma has not yet relaunched dine-in, and Karatassos said the company “is going to wait to see how things go” before making a decision at that restaurant. Chops Lobster Bar and Pricci are operating their dining rooms with limited capacity. [NOTE: Chops and Pricci are two very high-end restaurants]
- After mandating Georgia dining rooms to close April 1, Kemp allowed the state’s restaurants to resume dine-in service April 27. While many independent restaurants waited weeks before reopening — and some still have not — Buckhead Diner and Corner Cafe reopened their dining rooms in early May. They operated at 50% capacity for about a month before Buckhead Life decided to pull the plug. The restaurants will reopen their dining rooms once the social-distancing guidelines are lifted.
- “A lot of people have waited to open,” Karatassos said. “We reopened sooner, so we’ve learned some things here that others haven’t figured out yet, because they haven’t been open yet.”
- Buckhead Life has received Small Business Association Paycheck Protection Program loans for its restaurants, Karatassos said, though he did not disclose how much the company received.
- Buckhead Life has received rent deferments from its landlords, but that is not a long-term solution, Karatassos said.
- “I’m not sure how any restaurants — cafes, call them; lunch, breakfast spots; mom-and-pop-style restaurants that are full service that are low-check average, casual — how they can survive with the seating like this,” he told the Chronicle. “It’s just not sustainable.”
- “Customers have a choice on whether to come out or not to come out,” he said. “They have a choice of going to Costco and Target. They have a choice of going to the mall. I think shortly the six-foot rule of separation on tables needs to go away, and if somebody’s not comfortable, they have a choice of not going out. I think those people are not going out whether there’s six feet or not.”
K. Projections & Our (Possible) Future
1. Social bubbles may be the best way to emerge from lockdown
- Holing up with groups of friends or neighbors or other families during lockdown has given many people, especially those stuck home alone, a way to relieve isolation without spreading C19. These groups are known as bubbles, and new computer simulations described in Nature today show they may really work.
- As countries around the world leave or get ready to leave lockdown, we need to come up with ways to mix with other people without causing another spike in C19 infections, one that balances public health concerns with our social, psychological, and economic needs to interact.
- How to do that isn’t clear. Medical advisors recommend measures such as sheltering in place, avoiding people outside your household as much as possible, and keeping two meters apart when you do interact.
- Yet there is little research on the effectiveness of such social distancing. Previous studies have mainly looked at the impact of broad restrictions, such as stopping travel, canceling public gatherings, and closing schools—not the specifics of social interaction at a person-to-person level.
- A team led by Per Block, a sociologist at the University of Oxford and the Leverhulme Centre for Demographic Science in the UK, simulated three different social distancing strategies and found that each gave a way to extend our social circles while keeping transmission of C19 relatively low—as long as we still stick to certain rules.
- The first strategy is mixing only among people with something in common, such as those who live in the same neighborhood or are the same age. Grouping employees together this way could reduce the risk of widespread transmission when businesses reopen, the researchers suggest.
- The second strategy is to stick to groups that already have strong social ties, such as friends who are also friends with each other.
- The third strategy the team simulated was bubbling, in which a group chooses its own social circle—and then everyone stays within it.
- All three strategies were more effective at reducing transmission than random social distancing, where people reduce the number of people they see but still come in contact with a few individuals from different groups.
- But according to the simulations, bubbles are the best of the bunch: they delay peak infection rate by 37%, decrease the height of the peak by 60%, and result in 30% fewer infected individuals overall. The first strategy, sticking to a group of people with something in common, was the second most effective.
- The researchers suggest that bubbles work well because they are built on a deliberate choice about who you will and won’t interact with, rather than depending on less deliberate social or geographic ties, which are more easily broken.
- Of course, sims are not real life. For a start, the researchers modeled relatively small networks of between 500 and 4,000 people. But the size did not make a significant difference to the effectiveness of the various strategies, which suggests that the results might also hold true for much larger populations.
- There’s also the question of public messaging: social distancing works best when the guidelines are as simple as possible. Muddying the message with more complicated rules may not work so well in reality.