May 24, 2020
Happy Memorial Day!
Featured Story Index and 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.
- New Scientific Findings & Research
- 35% asymptomatic, 0.4% with symptoms will die
- Are We Expecting Too Much From Vaccines?
- Massive vaccine testing planned to meet year-end deadline
- Early study of C19 vaccine developed in China sees mixed results
- Projections & Our (Possible) Future
- Good News, Or False Hope?
- Lockdowns vs. Reopenings
- Lockdowns Are Costing Us — It’s Time to Be Smart
- Reopenings: Progress & Setbacks
- Reopenings in Georgia, Florida & Texas: So Far, So Good
- Herd Immunity?
- Surprising Finding: Just 7.3% of Stockholm had C19 antibodies by end of April
- Study details benefits and limitations of remdesivir
- Coronavirus patients treated with hydroxychloroquine at higher risk of death
- John Hopkins Daily COVID-19 Update (see Annex I)
- You can access all of the updates at any time on our website at https://dailyC19post.com/. You can also access the updates at any time on Facebook at https://www.facebook.com/groups/2467516816834782//. 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.
- As there is a lot of inaccurate information circulating, we only include information that we can confirm from a credible source or that is based on data that we can verify. To the extent that we derive information from an online source, we provide a link to the source, which typically provides more detail that is included in our update. If you have any questions about any information included in an update, or if you have a different view, please let me know and we will supplement or correct as needed.
- We do not endorse or necessarily agree with any opinion or view included in this Update. We include a wide spectrum of opinions as we believe that it gives perspective on what people are thinking and may give insights into our future.
- The NY Times provides a good overview of which States are locked down and which are reopening, and where each State is in the process of reopening, see https://www.nytimes.com/interactive/2020/us/states-reopen-map-coronavirus.html.
A. A Glance At Our World Through Headlines
- Dr. Fauci: ‘Most of the Country’ Reopening ‘in a Prudent Way’ – ‘Prolonged’ Lockdowns Aren’t the Way to Go
- Dr. Fauci: Overextending lockdowns may cause ‘irreparable damage’
- U.S. Census Launches Weekly Coronavirus Report: 47% Jobless, 38% Delayed Medical Treatment
- Justice Department Warns Los Angeles Stay-at-Home Extension Could be Illegal
- Trump orders all places of worship to open, declaring them essential
- NY Gov. Cuomo: New York reports lowest daily coronavirus death toll in two months
- Beaches reopen in Portugal as lockdown slowly eased
- Kuwait raises fine for not wearing facemask to 16k
- Washington Post cites study claiming 24 states at risk for ‘second wave’
- Italy ways reopening different regions at different speeds
- Many more young people dying in Brazil, developing world vs. US
- PM Johnson pressured to fire top advisor for ‘violating’ quarantine rules
- Japan to completely lift state of emergency nationwide on Monday
- Cali court upholds state order to close churches
- Brazil, Russia in No.2, No.3 spots after US
- Russia case total tops 335,000
- Long Island might reopen as soon as Wednesday
- Nearly 9% of prisoners in Michigan test positive
- Coronavirus resisters could get violent if lockdowns drag on, feds warn
- NBA restarting season at Disney World is almost done deal
- GOP Senators mock House Dems for not coming to work amid coronavirus fears
- Britain, France issue strict quarantine rules for post-pandemic travel
- DOJ intervenes in lawsuit challenging Illinois coronavirus lockdown
- Health Department hits NYC nursing home with violations after Post report
- GOP Senators mock House Dems for not coming to work amid coronavirus fears
- Multiple Los Angeles Area Casinos Reopen for Memorial Day Weekend
- Interior Secretary Opens National Parks for Memorial Day Weekend
- Georgia Issues Coronavirus Filming Guidelines to Re-Start Production
- Michigander Posts ‘All Business is Essential’ Billboards Around State
- Whitmer Extends Safer-at-Home Order to June 12
- Over 80 Million Children at Risk as Coronavirus Disrupts Vaccination Schedules
- British Researchers Testing Experimental Vaccine on Thousands of People
- Spain will welcome foreign tourists in July: prime minister
- Las Vegas is reopening sooner than you think
- UN warns coronavirus pandemic may lead to spike in cyber crimes
- China reports first day of zero coronavirus related deaths
- San Francisco socially distances its homeless encampments amid coronavirus pandemic
- Memorial Day tempts Americans outdoors, raising virus fears
- Coronavirus pandemic shows how risk-averse Americans have grown
- The CDC’s continued screwups make it very hard to trust
- $21M Brooklyn field hospital never saw a patient amid coronavirus pandemic
- New York auto show officially canceled for 2020
- NY will not include ‘probable’ coronavirus fatalities in death toll
- Coronavirus pandemic gives consumers a break from robocalls
- Portuguese resort to test all residents ahead of summer season
- De Blasio says shuttered businesses will be able to hang on for months
- East Africa fears ‘triple threat’ from coronavirus, floods and locusts
- UN reports Yemen’s health system ‘has in effect collapsed’
- White House economist expects US to see ‘highest growth’ ever in 3rd quarter
- Cuomo says additional NY regions could reopen in days
- Tanzania says they defeated coronavirus through prayer
- Lockdown-fatigued New Yorkers flood parks, beaches
- Ohio to allow wedding receptions of up to 300 people starting in June
- Mets, Yankees would resume training in Florida ahead of proposed MLB season
- Bankruptcy Tsunami Begins: Thousands Of Default Notices Are “Flying Out The Door”
- COVID Sparks Sexbot “Revolution” As People Ditch Tinder
- Cannabis stocks sky high amid hopes weed wards off coronavirus
B. New Scientific Findings & Research
1. 35% asymptomatic, 0.4% with symptoms will die
- Asymptomatic C19 patients are of great concern to public health officials and lawmakers due to their ability to spread the virus without knowing they’re sick themselves.
- Now, the Centers for Disease Control and Prevention estimates that more than a third of C19 patients could be asymptomatic.
- The new guidance, which the agency says is “designed to help inform decisions by modelers and public health officials who utilize mathematical modeling,” lists five scenarios and notes scenario five, which has 35% of C19 patients as asymptomatic, as its “current best estimate.”
- It also notes that 0.4% of those who do show symptoms will die from the coronavirus.
- [Note: if 35% are asymptomatic and 0.4% with symptoms will die, then the fatality rate for those infected with C19 would be 0.26% [.65 x 0.004 = 0.0026]. Although a fatality rate of 0.26% would be 160% more than the 0.1% fatality rate for the flu [(0.26 – 0.1)/0.1 x 100], it is substantially less than the 2.0% to 3.4% lethal rates originally estimated.]
- The most at-risk group is people 65 and older, with the CDC saying it expects 1.3% of those who symptoms to die. The next most at-risk group is people between the age of 50 and 64, with the agency estimating 0.2% of these symptomatic patients will die.
- [Note: Consequently, the fatality rate for anyone 65+ infected with C19 is 0.845% [1.3 x .65], and the fatality rate for people between 50 and 64 is 0.13% [0.2 x .65].
- The CDC says these values are based on data received by the agency before April 29, and the numbers are subject to change as the pandemic goes into the later months of the year. As of Friday morning, more than 94,000 people have died in the U.S., according to data collected by Johns Hopkins University.
- The high number of asymptomatic patients has led to concerns of a so-called “second wave” of the coronavirus pandemic cropping up later this year, which as led some to suggest rolling on and off lockdowns to deal with the pandemic.
- Earlier this month, the CDC said there was mounting evidence that suggests the novel coronavirus can be transmitted from pre-symptomatic or asymptomatic individuals, bolstering the argument for maintaining proper social distancing measures and possibly impacting the case-fatality rate for C19.
- In April, the CDC estimated some 25% of cases could be asymptomatic. However, that number varied for different groups, including as high as 70% for military personnel, according to the Vice-Chairman of the Joint Chiefs of Staff, Gen. John Hyten.
2. Coronavirus immunity could disappear after six months
- Immunity to the coronavirus could only last up to six months, scientists say.
- A study at the University of Amsterdam found that those who survived the coronavirus could become reinfected within six months, casting doubt on the concept of “immunity passports” to allow survivors of the virus to return to normal life, according to a report in The Science Times.
- For 35 years, University of Amsterdam scientists, led by Lia van der Hoek regularly tested 10 men for four coronaviruses that cause the common cold. While most were reinfected within three years, there were “significant” drops in antibody levels after six months, the study found.
- “Coronavirus protective immunity is short-lasting,” van der Hoek said. “We saw frequent reinfections at 12 months post-infection and substantial reduction in antibody levels as soon as six months post-infection. Achieving herd immunity may be challenging due to rapid loss of protective immunity.”
1. Are We Expecting Too Much From Vaccines?
- With a little luck and a lot of science, the world might in the not-too-distant future get vaccines against C19. But those vaccines won’t necessarily prevent all or even most infections.
- In the public imagination, vaccines are often seen effectively as cure-alls, like inoculations against measles.
- Rather than those vaccines, however, the C19 vaccines in development may be more like those that protect against influenza — reducing the risk of contracting the disease, and of experiencing severe symptoms should infection occur, a number of experts told STAT.
- “We all recognize that flu vaccine, in a year when it’s efficacious, you have what, 50% protection? And in a year when it’s poor you have 30% or less than that — and still we use that,” said Marie-Paule Kieny, who is chairing a committee advising the French government on vaccines to prevent C19.
- Ideally, vaccines would prevent infection entirely, inducing what’s known as “sterilizing immunity.” But early work on some of the vaccine candidates suggests they may not stop infection in the upper respiratory tract — and they may not stop an infected person from spreading virus by coughing or speaking.
- A recently released study in which macaques were vaccinated with one vaccine candidate — this one being developed by Oxford University and AstraZeneca — showed the primates were protected from Covid-induced pneumonia. But the macaques still had high levels of virus replicating in their upper airways. (The paper was a pre-print, meaning it hasn’t yet been peer-reviewed and published in a journal.)
- Vincent Munster, who leads the team that conducted that study, said a vaccine that could mitigate the severity of the C19 pandemic would still be a significant contribution in a world struggling to co-exist with a dangerous new virus.
- “If we push the disease from pneumonia to a common cold, then I think that’s a huge step forward,” said Munster, chief of the virus ecology unit at the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories in Hamilton, Mont.
- The rush to develop vaccines means that ideal solutions may be out of reach in the immediate term; Munster said he anticipates seeing second-generation vaccines that could be more protective. Other scientists, though, are cautious about how much the world can expect from vaccines against this pathogen.
- Michael Mina, an infectious diseases epidemiologist at Harvard’s T.H. Chan School of Public Health, thinks achieving sterilizing immunity with a vaccine will not be possible for C19. Experience with human coronaviruses — and with multiple pathogens that cause colds — shows immunity that develops after infection with respiratory tract infections is not lifelong. In some cases, the duration is measured in months, not years.
- “If [infection with] natural coronaviruses doesn’t do it, I don’t think that we should necessarily expect or have the anticipation that we’ll be able to get there with the vaccine,” said Mina, who is also associate medical director of clinical microbiology at Boston’s Brigham and Women’s Hospital.
- Munster agreed trying to develop vaccines that confer sterilizing immunity would be a heavy lift with this coronavirus. “I think we really need to focus on what are the fastest achievable true public health goals of the vaccine, which is protecting the vulnerable people against pneumonia and protecting health care workers as well,” he said.
- Earlier this week Moderna, the Cambridge, Mass.-based biotech, said eight people in a Phase 1 trial of its C19 vaccine developed neutralizing antibodies to the virus.
- Neutralizing antibodies should protect against severe C19 disease, Kanta Subbarao, a vaccine expert who is director of the World Health Organization’s influenza collaborating center in Melbourne, Australia, recently wrote in a commentary in the journal Cell Host and Microbe.
- But Subbarao told STAT she wouldn’t be surprised if neutralizing antibodies don’t protect against infection in the upper airways. Like Munster, she doesn’t think that’s reason not to pursue these vaccines.
- “Converting this infection to an upper respiratory illness would be, I think, quite a lot better than where we are today,” said Subbarao, who worked on vaccines for SARS, a closely related coronavirus that caused an international outbreak in 2003.
- Subbarao said setting public expectations of what these vaccines will be able to achieve is critical.
- It would not be helpful if the type of perception that exists about flu vaccines — that they don’t work very well — sets in with C19 vaccines. People don’t credit flu vaccines for what they prevent; they deride flu shots for not protecting them on the occasions when they contract influenza, even though they have been vaccinated.
- “We can’t leave all that messaging until we know how good the vaccines are,” Subbarao said. “I think that will be the messaging, that we’re not going to prevent all infection. We’re going to prevent disease.”
- The fact that the macaques that Munster’s group vaccinated and then infected had virus in their upper airways was viewed with dismay by some. But Munster noted the animals were infected with large doses of virus; whether the same will be true in people remains to be seen.
- Some experts hope that even if the vaccines don’t prevent infection in the upper airways, they may reduce the amount of virus a vaccinated person generates and emits.
- “Hopefully it would diminish — although we don’t know this — the levels of replication on the mucosal surfaces,” said Mark Feinberg, CEO of the International AIDS Vaccine Initiative, which is working to develop an orally administered C19 vaccine. That route of administration may improve the vaccine’s capacity to protect the mucus membranes of the upper airways.
- Mina sees a potential upside to C19 vaccines that don’t stop infection and transmission, saying low-level circulation of the virus could act as a natural “booster” to keep people’s immunity levels high.
- “Then you don’t necessarily have to keep going and getting a vaccine every year, for example. You could rely on some level of natural exposure as long as all the people who are at particular risk have been given the opportunity to be vaccinated as well,” he said.
- But there’s the rub, warned Sarah Fortune, chair of the department of immunology and infectious diseases at Harvard’s School of Public Health.
- “It’s a little bit sobering to see that, while we may get protection against disease [and] protect people from getting sick, we may not get nearly as effective protection against transmission,” Fortune said during a briefing Thursday for reporters.
- “Which means that to protect the population, we’re going to have to be vaccinating many, many more people, because we can’t rely on getting to a lot of people and having the epidemic die out through herd effects.”
2. Massive vaccine testing planned to meet year-end deadline
- The United States plans a massive testing effort involving more than 100,000 volunteers and a half dozen or so of the most promising vaccine candidates in an effort to deliver a safe and effective one by the end of 2020, scientists leading the program told Reuters.
- The project will compress what is typically 10 years of vaccine development and testing into a matter of months, testimony to the urgency to halt a pandemic that has infected more than 5 million people, killed over 335,000 and battered economies worldwide.
- To get there, leading vaccine makers have agreed to share data and lend the use of their clinical trial networks to competitors should their own candidate fail, the scientists said.
- Candidates that demonstrate safety in small early studies will be tested in huge trials of 20,000 to 30,000 subjects for each vaccine, slated to start in July.
- Between 100,000 and 150,000 people may be enrolled in the studies, said Dr. Larry Corey, a vaccine expert at Fred Hutchinson Cancer Center in Seattle, who is helping design the trials. “If you don’t see a safety problem, you just keep going,” Dr. Francis Collins, director of the National Institutes of Health (NIH), told Reuters. The vaccine effort is part of a public-private partnership called Accelerating C19 Therapeutic Interventions and Vaccines (ACTIV) announced last month.
- The effort fits into the research and development arm of “Operation Warp Speed,” the White House program announced last week to accelerate coronavirus vaccine development. Vaccines, which are intended for use in healthy people, are typically tested in successive steps, starting with trials in animals.
- Human testing begins with a small safety trial in healthy volunteers, followed by a larger study to find the right dose and get an early read on efficacy. The final stage consists of large-scale testing in thousands of people. Only then would a vaccine developer commit to manufacturing millions of doses. In the era of coronavirus, many of those steps will overlap, particularly the mid-stage and late-stage trials, Collins and Corey said.
- The approach has its risks, as certain safety issues may only appear in large-scale trials. Americans are concerned about the speed of the vaccine effort, a Reuters/Ipsos poll showed. A highly effective vaccine could be tested in as little as six months if there is a big difference in benefit between the vaccine and placebo groups, Corey said. For a modestly effective vaccine, trials could take nine to 12 months.
- The U.S. government has committed billions of dollars to help manufacturers produce doses of vaccines that may never prove successful.
- To get the quickest answer, vaccines will be tested in healthcare workers and communities where the virus is still spreading to show whether they reduced new cases of C19. Washington, D.C, which has not reached the peak of its outbreak, is one likely test site. Trials may be conducted abroad, including in Africa, where the virus has just started to spread, Collins said.
- The government plans to tap its own trial networks, including the Department of Veterans Affairs’ 100 healthcare facilities, for potential study volunteers, while drugmakers will recruit from their clinical research networks.
- A Moderna Inc vaccine, developed in partnership with the NIH, will be the first to the enter large-scale testing in July, and may be joined by a vaccine from Britain’s Oxford University and AstraZeneca Plc, Collins said.
- The U.S. government said on Thursday it would spend $1.2 billion to secure 300 million doses of the Oxford vaccine. “What we might try to do is run those two side by side, but with a control arm” that would also include 10,000 healthy individuals who got a dummy vaccine, Collins said. Moderna’s candidate is already proceeding to mid-stage human trials. Vaccines by Johnson & Johnson, Sanofi and Merck & Co are a month or two behind the frontrunners and “may get added over the course of the summer” following early-stage human trials, Collins said.
- Merck has not made any specific announcements on its vaccine program and declined to comment.
- Collins would not name other candidates on the U.S. shortlist of 14, but said they will need to finish early safety testing by this summer to make it into the bigger trials. Trials will need to assess if the vaccines cause disease enhancement – a potentially dangerous side effect in which the vaccine makes the disease worse in some individuals instead of preventing it. Disease enhancement has been seen in animal studies of vaccines developed to fight a close cousin of the virus that causes C19. “If there is enhancement, that’s a big stop sign for everything,” said Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases at NIH.
- “If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Fauci said.
3. Early study of C19 vaccine developed in China sees mixed results
- C19 vaccine candidate being developed by a Chinese drug maker appeared to induce an immune response in subjects, but also showed some concerning although not unexpected results.
- Data on the vaccine, made by CanSino Biologics, were published Friday in the Lancet, the first time Phase 1 trial data from any C19 vaccine have been published in a scientific journal. The results are likely to be closely examined, particularly in Canada, which recently announced it would test the vaccine and produce it there if results of the early studies were positive.
- The study found that one dose of the vaccine, tested at three different levels, appeared to induce a good immune response in some subjects. But about half of the volunteers — people who already had immunity to the backbone of the vaccine — had a dampened immune response.
- The vaccine is what’s known as a viral vector vaccine; it uses a live but weakened human cold virus, adenovirus 5, onto which genetic material of the coronavirus has been fused. The Ad5 virus is effectively a delivery system that teaches the immune system to recognize the coronavirus.
- But many people have had previous infections with adenovirus 5, raising concerns that the immune system would focus on the Ad5 parts of the vaccine rather than the coronavirus part. Many research groups that work on viral-vectored vaccines stopped using Ad5 because of concerns about preexisting immunity, which can run to 70% or higher in some populations.
- “This is definitely one of the concerns about using vectored vaccines for which people might already have pre-existing immunity,” said Michael Mina, an infectious diseases epidemiologist at Harvard’s T.H. Chan School of Public Health.
- “If you already have seen a virus or have some pre-existing immunity to it … you run the risk of having your immune response get skewed and picking up primarily the thing you’re already immune to or that you’ve already seen and not focusing so much on the new aspect, which in this case would be the coronavirus proteins that were placed onto the adenovirus vector,” he said.
- In the study, Chinese scientists reported that while people who had high levels of preexisting immunity to Ad5 responded to the vaccine, the rise in antibodies to the coronavirus was less robust than among those in the study who had low or no preexisting antibodies to Ad5. They also showed antibodies to the adenovirus itself soared among people who had prior immunity, suggesting their systems views the vaccination as a boost of their Ad5 immunity.
- About half of the 108 people in the Phase 1 trial had high levels of pre-existing antibodies to Ad5. The problem was more common among subjects at the older end of the age range, among 45 to 60 year olds — a finding that raises questions about how well the vaccine would work in one of the demographic groups that most needs protection from this infection, older adults.
- “This probably wouldn’t be a vaccine that you would want to give to the people over 65, because they may have higher levels [of pre-existing immunity],” said Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.
- Gary Kobinger, director of the Infectious Disease Research Center at Laval University in Quebec, was not surprised by the findings.
- “This was the assumption and they are just demonstrating that the assumption was correct,” he told STAT, adding that he doesn’t expect this vaccine to succeed.
- Kobinger said CanSino — which also produced an Ebola vaccine using this viral vector — has argued it could override the problem of preexisting immunity by using higher doses of the vaccine or using an intra-nasal delivery mechanism, rather than injecting the vaccine into muscle. (In this study, the vaccine was injected.)
- But in the highest of the three doses used in this study, the number of side effects was high — 75% of the people in the highest dose arm reported at least one side effect. Side effects included fever — some higher than 101.3, which is considered a Grade 3 or serious side effect — pain at the injection site, headache, fatigue, among others. Ten volunteers had Grade 3 side effects, representing 9% of the overall study group, with 17% of the people in the arm receiving the highest dose of vaccine reporting Grade 3 reactions.
- The authors said the Phase 2 trial, which is already underway, is not using the highest of the three doses.
- The authors also reported that among subjects who had high preexisting levels of immunity to Ad5, only five (25%) participants in the low-dose group, seven (37%) participants in the middle-dose group, and 10 (63%) participants in the high-dose group had at least a fourfold increase in their levels of neutralizing antibody for the coronavirus 28 days after receiving the vaccine.
- Edwards acknowledged the findings relating to pre-existing immunity are “a cause for caution.”
- But she noted it is not yet clear what degree of an immunity response is needed to achieve protection against the virus that causes C19 — and maybe the antibody levels reached in people who had preexisting immunity to Ad5 will be high enough, even if they aren’t at the levels of people who had low level or no previous immunity to the vaccine vector.
- “This is the story of Ad5,” Edwards said. “It’s the concern with Ad5 that’s been there from the beginning: That if you have antibody to the vector, then you don’t get as good a [vaccine] take.”
- “Maybe this level of antibody is enough? I don’t know,” she added. “I think it’s reasonable to look at this and see what it does. It’s only a Phase 1 study.”
- The problem with pre-existing immunity is not the potential issue with the Ad5 vaccine vector.
- In 2007 a trial of an HIV vaccine using an Ad5 backbone was halted when it was seen that more people in the vaccine arms of the trial were becoming infected with HIV than those in the placebo arm. It remains unclear why that happened.
- The authors of the Phase 1 C19 trial noted the earlier troubling outcome, and said they will be monitoring for similar safety signals as they continue to study this vaccine.
- “Although the association between HIV-1 acquisition risk and Ad5-vectored vaccine is controversial and its mechanism is unclear, the potential risks should be taken into account in studies with this viral vector delivery platform,” they wrote. “We plan to monitor the participants in our upcoming phase 2 and phase 3 studies to assess the indication for any such acquisition.”
D. Concerns & Unknowns
1. Multisystem Inflammatory Syndrome in Children (MIS-C) associated with C19
What we know about MIS-C
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. We do not yet know what causes MIS-C. However, we know that many children with MIS-C had the coronavirus, or had been around someone with C19. MIS-C can be serious, even deadly, but most children who were diagnosed with this condition have gotten better with medical care.
- Abdominal pain
- Neck pain
- Bloodshot eyes
- Feeling extra tired
[Note: Be aware that not all children will have all the same symptoms.]
What to do if you think your child is sick with MIS-C
- Seek emergency care right away if your child is showing any of these emergency warning signs of MIS-C or other concerning signs:
- Trouble breathing
- Pain or pressure in the chest that does not go away
- New confusion
- Inability to wake or stay awake
- Bluish lips or face
- Severe abdominal pain
How doctors will care for your child
- Doctors may do certain tests to look for inflammation or other signs of disease. These tests might include:
- Blood tests
- Chest x-ray
- Heart ultrasound (echocardiogram)
- Abdominal ultrasound
- Doctors may provide supportive care for symptoms (medicine and/or fluids to make your child feel better) and may use various medicines to treat inflammation. Most children who become ill with MIS-C will need to be treated in the hospital. Some will need to be treated in the pediatric intensive care unit (ICU).
- Parents or caregivers who have concerns about their child’s health, including concerns about C19 or MIS-C, should call a pediatrician or other healthcare provider immediately. Healthcare providers can follow CDC recommendations to keep children and their parents or caregivers safe if an in-person visit is needed.
E. Projections & Our (Possible) Future
1. Good News, Or False Hope?
[Note: The White Paper underlying this story can be found at file:///C:/Users/Pat%20Duval/Downloads/COVID19PredictionPaper.pdf. We have also attached a copy of the White Paper to this Update.]
- The Singapore University of Technology and Design has created a mathematical model which predicts future infections of C19 using data from current confirmed cases and deaths.
- The model – based on a ‘predictive-monitoring’ technique – inputs cases and deaths worldwide and visualizes the data in a bar chart. A bell-shaped curve over the top displays the projected trajectory of the disease, including peak, acceleration and deceleration.
- As of predictions on April 30, the UK is predicted to be coronavirus-free by August 27, Singapore is earlier at June 28, and the US is later at September 20.
- The model predicted a 100% end to the pandemic on a worldwide scale around December 4.
- Scientists making the predictions however have stressed that predictions are open to change and the dates are not definite.
- The team said the model is ‘inaccurate to the complex, evolving and heterogeneous realities of different countries’ and that ‘predictions are uncertain by nature’. This is due to a number of factors, including the strengthening of restrictions in some places and the relaxing of measures in others, people not adhering to the measures or protests against lockdown.
- The report added: ‘Over-optimism based on some predicted end dates is dangerous because it may loosen our disciplines and controls and cause the turnaround of the virus and infection, and must be avoided.’
- It comes as experts predicted the UK could be recording zero deaths from coronavirus from June, and there were no new cases recorded in London on Monday. Professor of evidence-based medicine at the University of Oxford, Carl Heneghan, predicts there will be a sporadic rise and fall in deaths over the next four to six weeks but does not expect to find coronavirus listed in the ONS death data by the end of June.
- Speaking at a briefing this week he said: ‘I think by the end of June we’ll be looking at the data and finding it difficult to find people with this illness, if the current trends continue in the deaths. ‘But we will continue to have these sporadic up and downs for about four to six weeks.’
2. Imperial College: Epidemic Is Not Under Control in Much of the US
- As of 20 May 2020, the CDC reported 91,664 confirmed or probable C19-related deaths, more than twice the number of deaths reported in the next most severely impacted country. In order to control the spread of the epidemic and prevent health care systems from being overwhelmed, US states have implemented a suite of non-pharmaceutical interventions (NPIs), including “stay-at-home” orders, bans on gatherings, and business and school closures.
- We model the epidemics in the US at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the time-varying reproduction number (the average number of secondary infections caused by an infected person), the number of individuals that have been infected and the number of individuals that are currently infectious. We use changes in mobility as a proxy for the impact that NPIs and other behavior changes have on the rate of transmission of the coronavirus. We project the impact of future increases in mobility, assuming that the relationship between mobility and disease transmission remains constant. We do not address the potential effect of additional behavioral changes or interventions, such as increased mask-wearing or testing and tracing strategies.
- Nationally, our estimates show that the percentage of individuals that have been infected is 4.1% [3.7%-4.5%], with wide variation between states. For all states, even for the worst affected states, we estimate that less than a quarter of the population has been infected; in New York, for example, we estimate that 16.6% [12.8%-21.6%] of individuals have been infected to date. Our attack rates for New York are in line with those from recent serological studies broadly supporting our modelling choices.
- There is variation in the initial reproduction number, which is likely due to a range of factors; we find a strong association between the initial reproduction number with both population density (measured at the state level) and the chronological date when 10 cumulative deaths occurred (a crude estimate of the date of locally sustained transmission).
- Our estimates suggest that the epidemic is not under control in much of the US:
- as of 17 May 2020, the reproduction number is above the critical threshold (1.0) in 24 [95% CI: 20-30] states. Higher reproduction numbers are geographically clustered in the South and Midwest, where epidemics are still developing, while we estimate lower reproduction numbers in states that have already suffered high COVID-19 mortality (such as the Northeast). These estimates suggest that caution must be taken in loosening current restrictions if effective additional measures are not put in place.
- We predict that increased mobility following relaxation of social distancing will lead to resurgence of transmission, keeping all else constant. We predict that deaths over the next two-month period could exceed current cumulative deaths by greater than two-fold, if the relationship between mobility and transmission remains unchanged. Our results suggest that factors modulating transmission such as rapid testing, contact tracing and behavioral precautions are crucial to offset the rise of transmission associated with loosening of social distancing.
- Overall, we show that while all US states have substantially reduced their reproduction numbers, we find no evidence that any state is approaching herd immunity or that its epidemic is close to over.
F. Lockdowns vs. Reopenings
1. Lockdowns Are Costing Us — It’s Time to Be Smart
- Lockdowns, as broad and untargeted measures that affect the entire population, generate a huge cost. By their very nature they imply massive, damaging consequences for employment, incomes, and economic activity generally. They also directly and indirectly create health and social costs. Cancers go unscreened and therefore untreated; children go uneducated, and even go hungry. There is an alternative: targeted measures that aim at enabling normal life to continue as much as possible.
- Call them “smart” measures. They focus most on protecting specific groups in the population that are most at risk. There is now overwhelming evidence that the elderly and otherwise vulnerable suffer higher mortality rates than others, many of whom face very low mortality rates, and that mortality rates among children are negligible. Risks of death have risen as a result of the existence of the virus for all age groups other than the elderly, but they are still in absolute terms low. Now that the possibility of complete suppression of the disease has become unlikely, at least until a vaccine or other solution emerges, there will remain some risk for all of contracting the disease. But through suitable efforts its prevalence can be limited, and more importantly its worst outcomes can be avoided.
- We should start by creating a protective belt around the most vulnerable. An example, although it is being implemented very late, is the idea of testing nursing-home workers for the virus regularly. Far from minimizing risks, many nursing homes appear to have been run in a fashion that contributed to them.
- Smart policies should aim to enable desired behaviors by providing support for those people for whom it is most important, both by removing obstacles to taking protective actions and by creating incentives that encourage them. Economists have clunky terms for these, referring to the former as the “participation constraint” and the latter as the “incentive compatibility constraint” that is involved when getting individuals to act in preferred ways. Are elderly people leaving the home to get essentials? It should be arranged to have them delivered instead. Intergenerational households are a particular problem; younger family members may need to go out and work, but when they do, they risk infecting their parents or grandparents. The smart policy would be to replace the incomes of those younger family members so that they can stay at home, or provide them with temporary accommodation elsewhere. The costs of such measures are sure to be small in comparison to those created by an untargeted lockdown.
- Many other examples can be thought of, and some are being implemented as discussion mounts about how to reopen schools, workplaces and communities. What’s missing is a way of understanding what unifies these approaches: a strategic direction that makes possible a reopening and at the same time protects lives. Although smart policies can use technology, such as testing, they are at their heart about implementing efforts in a specific and targeted way.
- The economic case for smart policies is that by focusing incremental efforts where there is greatest incremental risk they can achieve the goal of minimizing deaths at the least overall cost to society. Although benefits and cost are economic concepts, they should not be understood here in a narrowly economic way, but rather in terms of the overall well-being of society. If deaths can be kept to the same number or lower by more focused and less socially costly efforts than with a general lockdown, then it’s easy to see the value of the targeted approach. The case for replacing a broad lockdown with smart policies is clearer still if we consider deaths from all sources, as we should. For instance, vaccination rates in countries around the world are dropping, as outreach programs close or parents keep their children from routine doctor’s visits. Children’s vaccinations in New York City dropped by 63% over six weeks, raising the risk of an entirely preventable outbreak of whooping cough.
- It cannot be guaranteed that replacing lockdowns with smart measures would diminish deaths overall, even if they reduce some significant social costs, such as foregone education. But we do not always automatically prioritize the extension of lives over all other goals. The quality of life also matters, as do liberties. We take account of how decisions that might prospectively extend some lives are likely to affect others’ lives in other ways. If we did not do so, then we should spend all we have on health care. But regardless of the weights one places on different goals, if smart policies can make it possible to achieve them to a similar extent with lesser costs, then they must be considered.
2. What is America’s Virus Strategy?
- Nearly every country has been able to flatten the curve and/or taken steps to get the virus under reasonable control. This is critical so as to protect its hospitals from being overrun, thereby saving lives because they have the capacity and the capability to treat virus victims in addition to the rest of the community who need access to medical care.
- Once that has been established, there are two clear, but diametrically opposed strategies each nation can choose to take towards one day getting to a place where even older and vulnerable individuals can eat at a restaurant comfortably.
- Path A:
- On one hand, we can attempt to strictly distance and massively alter the quality of life for most Americans for extended periods of time in hopes of keeping the overall infection rate across the nation from going much higher than the 3-10% it probably is today until some uncertain day in the future where we develop a vaccine that works 100% of the time.
- Plan B:
- We protect the vulnerable population and then allow and even encourage the rest of the population to get back to normal life.
- With proper coordination, I can envision popular recording artists hosting virus relief concerts where young and healthy people go and hopefully get the virus and then the antibodies which allow them to donate blood to be used as a treatment or a prophylactic. Some of these people may even benefit as they are new to learn they have some compromise in their immune system.
- Citizens that don’t feel comfortable reengaging in the economy are free to wear masks and gloves to the grocery store and continue to shelter in place. Widespread testing should be available soon, so we know if it’s safe to visit our friends and family.
- But in plan B, those citizens that are comfortable go back to life as we know it with no restrictions. Individuals protect themselves and their families if they are worried. Businesses and institutions protect their employees including the vulnerable the best way possible.
- In choosing between these paths, it is important as a nation to understand that in large part we do need to pick one strategy or the other quickly. A country not sure what its strategy is will produce a very sub optimal outcome. And a country that lets partisan politics get in the way of such an important decision risks the worst-case outcome. In my mind, the choice is obvious and clearly Plan B for so many reasons, not the least of which is that it is the path least likely to lead to civil unrest. Path A is the path some politicians, some scientists and some physicians are advocating for, yet it is fraught with so many obvious risks and dire consequences.
- An effective vaccine scaled to produce 100’s of millions of vaccines is a long way away and may not be able to account for the virus mutating.
- Also, there is a significant societal cost in lost lives, lost quality of life and permanently lost productive capacity of our economy in trying to get to this uncertain point. How many elective procedures and regular screening protocols are delayed or eliminated as a result of shelter in place and distancing fears and what lives does that cost?
- At a minimum we all need to have this debate because we must make a choice and at a maximum, we need to quickly shift the strategy for Plan B. And to be clear, Plan B is just that, a plan. A phased, yet quick strategy to open up so we continue to protect hospitals and front-line workers.
- Nelson Mandela said it best: May your choices reflect your hope not your fears.
G. Reopenings: Progress & Setbacks
1. Reopenings in Georgia, Florida & Texas: So Far, So Good
- Three large Southern states that moved aggressively to reopen amid the coronavirus crisis have seen new cases and deaths largely hold steady since then — despite several controversies over some of their data.
- In Georgia, where Gov. Brian Kemp bucked the White House and local officials to lift a stay-at-home order on April 24, the state reported 862 cases on Thursday, according to the Atlanta Journal-Constitution.
- That was less than the 946 new cases counted on Wednesday, but helped spur a slight rise in a seven-day rolling average that’s been basically trending downward since the start of the Peach State’s reopening. [NOTE: Current hospitalizations are down more than a third from their highs in early March.]
- Deaths, meanwhile, rose by 78, marking the most since the same number was reached on April 27 and bringing the total toll to 1,775.
- Georgia set its single-day record for coronavirus deaths — 94 — before the lockdown, on April 20.
- Also Thursday, Kemp said he’d ordered an official review into how the state was compiling its numbers, following the revelation that the Department of Public Health included the results of 57,000 antibody tests in its data “since early April.”
- The snafu produced potentially misleading information because antibody tests can only confirm previous exposure to the coronavirus, not an active infection.
- “We’re not perfect. We make mistakes,” Kemp said.
- The bungle followed at least three others involving Georgia’s coronavirus information, including a since-corrected chart that wrongly showed steady declines in new cases because the dates weren’t listed in chronological order.
- In neighboring Florida, which this month saw some beaches abruptly closed after being swarmed by sun-worshippers, the Department of Health on Thursday confirmed 1,204 new cases among the state’s population of 29.5 million, bringing the total to 48,675, according to the Miami Herald.
- There were also 48 more C19 fatalities, pushing the Sunshine State’s death toll to 2,144.
- Florida — which was among the last states to impose a coronavirus lockdown, on April 2 — hit a record 1,413 new cases on April 16, followed by a record 83 deaths on April 28, according to the Tallahassee Reports website.
- Since the state began reopening on May 4, its seven-day average of new cases is essentially flat, according to a chart published by the New York Times.
- Gov. Ron DeSantis blamed Thursday’s spike in new cases — the highest since April 17 — on “another big dump” of more than 50,000 new test results.
- A DeSantis spokeswoman also tweeted that Rebekah Jones — who claims she was fired as the architect of the state’s digital coronavirus dashboard for refusing to doctor data to support the governor’s reopening plan — was “erratic” and “exhibits behavior unbecoming of a state employee.”
- DeSantis said Thursday that Jones was fired for insubordination and was “also under active criminal charges” for “cyberstalking and cyber sexual harassment.”
- In Texas, there were 945 new cases on Thursday, for a total 52,268, according to the Texas Tribune.
- The seven-day average of new cases rose fairly steadily from around 1,000 on May 1, when Gov. Greg Abbott began lifting the lockdown he ordered March 19, but began dipping on Sunday and is now around 1,250, according to a chart prepared by the Tribune.
- There were also 21 C19 deaths in the Lone Star State on Thursday, increasing the total number of fatalities to 1,440, the Tribune said.
- Meanwhile, Texas Supreme Court Justice Debra Lehrmann became the state’s first high-ranking official to be infected, based on positive test results for her and her husband after they suffered fevers and body aches early last week, the Dallas Morning News reported.
- Lehrman called the situation “perplexing,” telling the paper, “We have strictly adhered to the stay-at-home order since early March.”
H. Herd Immunity?
1. Surprising Finding: Just 7.3% of Stockholm had C19 antibodies by end of April
- Just 7.3% of Stockholm’s inhabitants had developed C19 antibodies by the end of April, according to a study, raising concerns that the country’s light-touch approach to the coronavirus may not be helping it build up broad immunity.
- The research by Sweden’s public health agency comes as Finland warned it would be risky to welcome Swedish tourists after figures suggested the country’s death rate per capita was the highest in Europe over the seven days to 19 May.
- Sweden’s state epidemiologist, Anders Tegnell, said the antibodies figure was “a bit lower than we’d thought”, but added that it reflected the situation some weeks ago and he believed that by now “a little more than 20%” of the capital’s population had probably contracted the virus.
- However, the public health agency had previously said it expected about 25% to have been infected by 1 May and Tom Britton, a maths professor who helped develop its forecasting model, said the figure from the study was surprising.
- “It means either the calculations made by the agency and myself are quite wrong, which is possible, but if that’s the case it’s surprising they are so wrong,” he told the newspaper Dagens Nyheter. “Or more people have been infected than developed antibodies.”
- Björn Olsen, a professor of infectious medicine at Uppsala University, said herd immunity was a “dangerous and unrealistic” approach. “I think herd immunity is a long way off, if we ever reach it,” he told Reuters after the release of the antibody findings.
- Tegnell has denied herd immunity is a goal in itself, saying Sweden aims instead to slow the spread of the virus enough for health services to cope. But he has also said countries that imposed strict lockdowns could be more vulnerable to a second wave of infections because a smaller percentage of their populations would be immune.
- In April, officials estimated one third of Stockholm residents would have contracted C19 by early May, subsequently suggesting that the capital could reach herd immunity of between 40% and 60% by the middle of June.
- Relying on citizens to act responsibly, Sweden has closed schools for the over-16s and banned gatherings of more than 50, but asked – rather than ordered – people to avoid non-essential travel, to work from home and stay at home if they are elderly or ill. Shops, restaurants and gyms have remained open.
- Polls show a large majority of Swedes support and are generally complying with their government’s more relaxed, less coercive strategy, which stands in stark contrast to the strict mandatory lockdowns imposed by many EU countries.
- Google records suggest trips to shops and cafes by residents of the Stockholm area are down 20%-40%, while passenger numbers on public transport have fallen by 30%-40%.
- But the approach has been heavily criticized by some Swedish academics as the number of coronavirus deaths in the country has risen, far exceeding those of its Nordic neighbors.
- While the overall coronavirus death rate per million is greater in Italy (535), Spain (597) or the UK (538), Sweden’s (376) is far in advance of Norway’s (44), Denmark’s (96) and Finland’s (55) – countries with similar welfare systems and demographics, but which imposed strict lockdowns.
- According to the scientific online publication Ourworldindata.com, C19 deaths in Sweden were the highest in Europe per capita in a rolling seven-day average between 12 and 19 May. The country’s 6.25 deaths per million inhabitants a day was just above the UK’s 5.75.
- The government’s decision to avoid a strict lockdown is thought unlikely to spare the Swedish economy. Although retail and entertainment spending has not collapsed quite as dramatically as elsewhere, analysts say the country will probably not reap any long-term economic benefit.
- The European commission has said it expects Sweden’s gross domestic product to contract by more than 6% this year, on a par with much of the continent, while the country’s central bank has estimated an even sharper fall of 7%-10%, with unemployment forecast to rise to as much as 10.4%.
- The World Health Organization has warned against pinning hopes on herd immunity as a means of containing the coronavirus, saying last week that studies had found antibodies in only 1%-10% of the global population.
- Critics such as Olsen say Sweden has done “too little, too late” and note that the government’s laissez-faire approach has been catastrophic for older people, with roughly half the country’s 3,831 deaths so far occurring in care homes.
- Tegnell’s predecessor as chief epidemiologist, Annika Linde, told Dagens Nyheter this week that the country’s strategy towards care homes had been “completely insufficient. The problems were underestimated. It was a clear misjudgment.”
- The government has admitted serious failings in care homes and this month announced a big increase in funding for the sector, but remains adamant that the country’s relatively high number of deaths per capita is not a consequence of its decision not to impose a lockdown.
1. Study details benefits and limitations of remdesivir
- Remdesivir, the only drug cleared to treat C19, sped the recovery time of patients with the disease, but its benefit appeared much more limited in patients who needed mechanical ventilation as part of their treatment, according to eagerly awaited results of a clinical trial.
- Initial results from the study, which led to the drug’s emergency authorization by the Food and Drug Administration, were released late last month. Full data were published late Friday in the New England Journal of Medicine.
- “It’s a very safe and effective drug,” said Eric Topol, founder and director of the Scripps Research Translational Institute. “We now have a definite first efficacious drug for C19, which is a major step forward and will be built upon with other drugs, [and drug] combinations.”
- But Topol noted that there was no sign of a benefit in patients who began the study with the most severe baseline status — those who were on non-invasive ventilation, who were intubated on a ventilator, or who were receiving extracorporeal membrane oxygenation, a treatment in which the oxygen is added to the blood outside the body. “We need to get something that works for these patients who have a high mortality rate,” Topol said.
- The study of 1,063 patients included 538 who received remdesivir and 521 who were given a placebo. Those who received remdesivir recovered in a median of 11 days, compared to 15 days for those who received placebo. Mortality in the remdesivir group was 7.1%, compared to 11.9% for the placebo group, but this difference was not statistically significant. This is slightly better than previous results.
- Remdesivir, developed by Gilead, has been in short supply, so the issue of which patients benefit most could be very important for deciding who receives the drug. The authors of the study argue that the difference in mortality rates resulted from the fact that there were fewer patients whose symptoms were more severe at the beginning of the study, resulting in less statistical power. But the benefit appeared much bigger among those who were less sick.
- The severity of patients’ illness was rated on a scale of 1 (not hospitalized) to 8 (dead). The lowest score in the study was a 4, denoting hospitalization, but no need for extra oxygen. The largest group of patients scored a 5, meaning they did need oxygen.
- Among patients who scored a 4, there was a 38% benefit in the speed of recovery. Among those who scored 5, there was a 47% benefit. But that benefit fell to 20% among those who scored a 6, meaning they were receiving high-flow ventilation, and a decrease of 0.05% among those who scored a 7, meaning they were intubated or on extracorporeal membrane oxygenation. Until more data are available, doctors and researchers are likely to debate whether to use remdesivir in sicker patients.
- There have been concerns that the study’s main goal, originally based on changes in the 8-point score at day 15, was changed before the result was analyzed. Changing goalposts can be a sign that researchers are skewing the results. In the paper, the researchers explain that the concern was that C19 illness was persisting much longer than had been expected. But that original goal, the odds of improvement in the 8-point scale on day 15, was 50% higher in the remdesivir group, a highly statistically significant result.
- Some critics saw flaws in the study that could affect how its results are interpreted. The study was stopped after a data safety and monitoring board, a panel of outside experts charged with safeguarding patients in the trial, notified the National Institute of Allergy and Infectious Diseases, which was running the study, that there had been a statistically significant benefit of remdesivir.
- The New England Journal paper does not say, as is normally the case, that the study was stopped. As STAT reported two weeks ago, some critics believe that the study should have continued in order to better discern whether remdesivir reduces the death rate.
- “It’s clear from the publication that the study was stopped prior to the completion of a significant number of patients,” said Steven Nissen, a cardiologist at the Cleveland Clinic. “By stopping it early the scientific community was deprived of the opportunity to determine whether remdesivir can or cannot reduce mortality.”
- According to the paper, as of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had finished 29 days of the study, recovered, or died. But there were still 132 patients in the remdesivir group and 169 in the placebo group who had not recovered or completed their follow-up visits. Nissen’s contention is that if the study had been allowed to finish, it would be more clear whether or not the drug improves patients’ odds of survival.
- Topol said that he interprets the survival benefit as “quite likely” and said he is “not bothered” by the fact that the mortality result is not significant. He said he awaits results from future trials.
- Peter Bach, a pulmonologist who is the director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, worried that it appears that slightly more placebo subjects started out in the more severe groups. This, he said, could mean that the overall effect is “potentially exaggerated.”
- “I am not concluding from this that the treatment is not reducing time to recovery; it makes me less convinced that there is a mortality benefit when more placebo than intervention ended up in the highest risk group,” Bach said. He pointed to another study of remdesivir, conducted in Wuhan, China, in which the time to benefit was not significant and there was no mortality benefit.
- Bach was critical of another study run by Gilead that lacked a placebo group, instead comparing two different durations of remdesivir treatment. He called the decision “frustrating.” Gilead has said that the decision was driven by limitations on its ability to produce vials of placebo that would have resembled the medicine.
- In a statement Friday, the company said results from a study that compares remdesivir to the standard of care in patients with moderate illness will be available by the end of the month.
2. Coronavirus patients treated with hydroxychloroquine at higher risk of death
- Hospitalized C19 patients treated with hydroxychloroquine had a higher risk of death compared to those who didn’t take it, according to a new study published Friday in The Lancet.
- Patients who took the drug or chloroquine, which hydroxychloroquine is derived from, were also more likely to developed irregular heart rhythms, according to the study. The study looked at more than 96,000 patients from 671 hospitals across six continents.
- Researchers at Harvard Medical School, Brigham and Women’s Hospital and other institutions looked at 96,032 patients who were hospitalized with C19 between Dec. 20 and April 14. They said 14,888 patients were treated with hydroxychloroquine or chloroquine, either alone or in combination with a macrolide. The remaining 81,144 patients were in the control group.
- Nearly 10,700 patients died in the hospital during the time period. The study found that after controlling for multiple factors, including age, race, sex and underlying health conditions, there was a 34% increase in risk of mortality for patients who took hydroxychloroquine and a 137% increased risk of serious heart arrhythmias.
- Hydroxychloroquine is known to have serious side effects, including muscle weakness and heart arrhythmia. A small study in Brazil was halted for safety reasons after coronavirus patients taking chloroquine, which hydroxychloroquine is derived from, developed arrhythmia, including some who died.
- Last week, another study published in the JAMA Network found the drug appeared to not help C19 patients and, instead, placed them at increased risk of cardiac arrest.
- The study published Friday analyzed medical records of C19 patients. It was not a randomized controlled trial, which is considered the gold standard in science. It was funded by William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.