Coronavirus Update

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Coronavirus Update 5-14

“Rule-making exists precisely to ensure that kind of controlling, subjective judgement asserted by one unelected official is not imposed in Wisconsin.” 

Chief Justice Patience Roggensack, Wisconsin Supreme Court, wrote in the majority opinion that struck down Wisconsin Governor administration’s stay at home order

“Today, Republican legislators convinced four members of the state Supreme Court to throw the state into chaos.”  

Wisconsin Governor Evers

“The rule of law must be upheld – even in emergencies.”  

 Former Wisconsin Governor Scott Walker

Today’s Features

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A. Recent Developments and Headlines

Sources: New York Times Coronavirus Updates, New York Post Coronavirus Updates, Zero Hedge Coronavirus Updates, Drudge, Breitbart, Wall Street Journal, Coronavirus White House Task Force Briefing, NY Governor Daily Briefing, and Worldometers

B. Numbers & Trends

Note: All changes noted in this Update are since the 5/13 Update

Sources: Worldometers

Visualizing Where COVID-19 Is Rising And Falling Around The World

1. Confirmed Total Cases, New Cases and Tests

  • Worldwide:  
    • Total Cases = 4,425,657 (+2.0%)
    • New Cases = 88,052 (+3.3%) (+2,772)
    • New Cases (5 day avg) = 83,273 (-1.8%) (-1,519)
  • US: 
    • Total Cases = 1,430,348 (+1.5%)
    • New Cases = 21,712 (-4.8%) (-1,090)
    • New Cases (5 day avg) = 21,713 (-6.4%) (-1,490)
    • Number of Tests = 10,269,996 (+334,276)

2. Deaths

  • Worldwide Deaths = 297,765 (+1.8%) 
    • New Deaths = 5,314 (+0%) (+0)
    • New Deaths (5 day avg) = 4,358 (-1.1%) (-47)
  • US Deaths = 85,197 (+2.1%) 
    • New Deaths = 1,772 (+8.7%) (+142)
    • New Deaths (5 day avg) = 1,316 (1.3%) (+16)
  • 5 Countries with Largest Number of Confirmed Deaths: 
CountryTotal DeathsDeaths Per 1M Population
US85,197 (+1,772)257 (+5)
UK33,186 (+494)489 (+7)
Italy31,106 (+195)514 (+3)
Spain27,104 (+176)580 (+4)
France27,074 (+83)415 (+7)
Worldwide297,765 (5,314)38.2
  • 5 Countries = 68.4% of Worldwide Total Confirmed Deaths (-0.3%)
  • US = 28.6% of Worldwide Total Confirmed Deaths (+0.1%)
  • 5 States with Largest Number of Confirmed Deaths: 
StateTotal  DeathsDeaths Per 1M Population
New York27,290 (+115)1,403 (+6)
New Jersey9,727 (+186)1,095 (+19)
Massachusetts5,315 (+174)771  (+15)
Michigan4,714 (+40)472 (+4)
Pennsylvania4,147 (+229)324 (+18)
US85,197 (+1,772)257 (+5)
  • 5 States = 60.1% of US Total Confirmed Deaths (-0.3%)
  • NY = 32.0% of US Total Confirmed Deaths (-0.6%)

3. Countries/States To Watch

  • Sweden [Note: The World Health Organization has cited the Swedish approach as a model for reopening economies]
    • Total Cases = 27,272 (+602)
    • Deaths = 3,313 (+57)
    • New Deaths (5 day avg) = 55 (-13.3%) (-8)
    • Deaths per 1M population = 328 (+6) 
  • Below are 5 of the States moving quickly to reopen their economies (and OK never locked down).   
StateTotal CasesTotal  DeathsDeaths Per 1M Pop
Georgia35,427 (+579)1,517 (+23)143 (+5)
Florida42,402 (+479)1,829 (+47)85 (+2)
Texas43,502 (+1,636)1,217 (+38)42 (+1)
Ohio25,729 (+465)1,485 (+47)127 (+4)
Oklahoma4,852 (+120)278  (+0)70 (+0)
US1,430,348 (+21,712)85,197 (+1,772)257 (+5)

C. New Scientific Findings & Research

1. Male coronavirus patients with low testosterone levels MORE likely to die from C19  

  • Men with low testosterone levels that contract C19 are at far greater risk of dying from the virus, a study has found. A recent study found men are twice as likely to die from the coronavirus, but clinicians have been unable to determine why this is. 
  • But a study from a German hospital of 45 C19 patients admitted to intensive care reveals the male sex hormone testosterone may play a key role. 
  • The hormone is known to help regulate the body’s immune response but when a man has low levels of testosterone, the immune system is not kept in check and can go haywire following infection. 
  • This leads to a so-called cytokine storm which happens when the immune system goes out of control as it tries to kill the pathogen.
  • A cytokine storm eventually begins damaging the body itself and, if left unchecked, can be fatal. 
  • The researchers assessed the first 45 laboratory-confirmed C19 patients admitted to the ICU at the University Medical Center Hamburg-Eppendorf. 
  • Thirty-five were men and ten were women, with seven patients requiring oxygen and 33 of them needing ventilation.  Nine men and three women died. 
  • Hormone levels of each patient were assessed on their first day in ICU, before they had received any invasive procedures. 
  • Samples from the C19 patients were tested for 12 hormones, including testosterone and dihydrotestosterone.  
  • Testosterone is key in how the body initiates and regulates various immune responses, including fighting viral infections.   
  • It plays a particular important role in men’s immunity as it is the main male sex hormone.
  • Of the male C19 patients sent to ICU at the German hospital, more than two thirds (68.6 per cent) recorded low levels of testosterone. 
  • In contrast, the majority of female patients (60 per cent) had elevated testosterone levels.
  • While low levels of testosterone can not control the immune response in men, the study found that in female C19 patients, higher testosterone levels were linked to a more significant inflammatory response.  
  • Professor Gülsah Gabriel from the Leibniz Institute for Experimental Virology in Hamburg, who was involved in the research, told MailOnline: ‘The majority of male C19 patients had low testosterone levels. 
  • ‘Of those male C19 patients who died, the majority also had low testosterone levels. 
  • ‘Thus, low testosterone levels in men seem to be a risk factor for severe and even fatal disease outcome in men upon infection with so-called “cytokine inducing” respiratory viruses.’  
  • SARS-CoV-2 trigger’s the human body into producing vast amounts of cytokines, chemicals which flood to the site of infection and begin fighting the pathogen. They can also signal to the body to send more immune cells to mount a defence against a foreign invader. 
  • It is a key part of healing in humans but a common issue for patients diagnosed with C19 is their immune system responds too aggressively.
  • This can lead to this process getting out of control as it tries to defeat the invading pathogen. It leads to an enormous immune response called a cytokine storm. 
  • This is a hyperinflammatory condition itself and can lead to severe lung damage, acute respiratory distress syndrome (ARDS) and death.
  • Ali Daneshkhah, a postdoctoral research fellow at Northwestern University who was not involved in the study, explains: ‘This is what seems to kill a majority of C19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system.’
  • Professor Gabriel adds: ‘It seems that testosterone has a dampening impact on the virus induced cytokine storm, which finally leads to death in both cohorts. ‘Men with normal testosterone levels do not present a cytokine storm and thus are more likely to survive.’ 
  • Writing in their study, which has not yet been peer-reviewed and scrutinised by independent academics, the medics say: ‘With SARS-CoV-2 continuing to infect humans worldwide, it was repeatedly reported that men with C19 are at higher risk to develop severe and even lethal outcome compared to women, independent of age.
  • ‘Thus, it has become of utmost importance to understand why men are more likely to die from C19 than women.’ 
  • The latest research builds on separate research, which Professor Gabriel was also involved in, which found men are also more likely to die after becoming infected with Avian influenza A (H7N9). 
  • Both these diseases are zoonotic — jumped into humans from animals — and are cytokine inducers, turning the body’s immune system against itself. 
  • ‘The current hypothesis is that this “cytokine storm” inhibits steroid synthesis leading to low testosterone levels in men,’ says Professor Gabriel. 

Source: Males with low testosterone levels are MORE likely to die of COVID-19 

D. Vaccines 

1. Moderna’s Coronavirus Vaccine Moves to Phase 2 Testing, and Gets Fast-Track Approval From the U.S. Government  

  • On May 12, Moderna Therapeutics, based in Cambridge, Mass., received fast-track approval from the U.S. Food and Drug Administration (FDA) for its C19 vaccine candidate, mRNA-1273. Days earlier, the FDA gave the company the green light to proceed to Phase 2 testing of the vaccine, which is expected to begin shortly. The company plans to launch the final stage of human testing, Phase 3, this summer, assuming the Phase 2 studies are complete, says Dr. Stephen Hoge, president of Moderna.
  • Fast-track designation boils down to a more expedited review process by the FDA. In particular, it means the agency can review data on a rolling basis so an entire application for approval isn’t held up until the final piece of data is collected and analyzed. “It’s validation that the FDA believes this is a very credible exercise,” says Hoge.
  • The Phase 2 studies will include around 600 healthy volunteers, half of whom are 18-55 years old and half of whom are over 55 years old. They will be randomly assigned to receive either placebo or one of two doses of Moderna’s experimental vaccine. Each participant will receive two shots—early studies suggest two injections might be necessary to jump-start the immune system to generate protection against the C19 virus. All the patients will then be followed for a year as the researchers monitor their immune responses.
  • Already, Moderna is thinking ahead towards the next steps should its vaccine receive FDA approval. “We have not hit major speed bumps or road blocks, so it’s been good so far,” says Hoge of developing and testing the vaccine. “But now as the data develops, we need to show that we can manufacture at scale, and we’re doing all we can to scale up to supply tens of millions of doses by the end of this year.”
  • Moderna’s vaccine relies on a relatively new technology based on the mRNA of the virus; it involves injecting fragments of the viral genetic material into the body, which then stimulates the body’s immune system to fight the novel coronavirus.
  • Public health experts anticipate that the coronavirus won’t dissipate any time soon, and believe that generating strong and widespread immunity to the virus, with the help of vaccines, will be essential in keeping the disease under control and reopening economies around the world. 
  • Currently, there are around eight vaccines being tested in people, using different technologies. Public health experts believe that multiple vaccines may be needed in order to meet global demand to immunize and protect as many people as possible from C19 in coming years.

Source: Moderna’s COVID-19 Vaccine Moves to Phase 2 Tests | Time

2. Get Ready for a Vaccine Information War  

By Kevin Roose, New York Times

Social media is already filling up with misinformation about a C19 vaccine, months or years before one even exists.

  • The other night, midway through watching a clip from “Plandemic” — a documentary that went viral on social media last week, spreading baseless lies and debunked nonsense about the coronavirus to millions of Americans overnight — I had a terrifying thought:
  • What if we get a Covid-19 vaccine and half the country refuses to take it?
  • It occurred to me that all the misinformation we’ve seen so far — the false rumors that 5G cellphone towers fuel the coronavirus, that drinking bleach or injecting UV rays can cure it, that Dr. Anthony Fauci is part of an anti-Trump conspiracy — may be just the warm-up act for a much bigger information war when an effective vaccine becomes available to the public. This war could pit public health officials and politicians against an anti-vaccination movement that floods social media with misinformation, conspiracy theories and propaganda aimed at convincing people that the vaccine is a menace rather than a lifesaving, economy-rescuing miracle.
  • Scariest of all? It could actually work.
  • I’ve been following the anti-vaccine community on and off for years, watching its members operate in private Facebook groups and Instagram accounts, and have found that they are much more organized and strategic than many of their critics believe. They are savvy media manipulators, effective communicators and experienced at exploiting the weaknesses of social media platforms. (Just one example: Shortly after Facebook and YouTube began taking down copies of “Plandemic” for violating their rules, I saw people in anti-vaccine groups editing it in subtle ways to evade the platforms’ automated enforcement software and reposting it.)
  • In short, the anti-vaxxers have been practicing for this. And I’m worried that they will be unusually effective in sowing doubts about a C19 vaccine for several reasons.
  • First, because of the pandemic’s urgency, any promising C19 vaccine is likely to be fast-tracked through the testing and approval process. It may not go through years of clinical trials and careful studies of possible long-term side effects, the way other drugs do. That could create an opening for anti-vaccine activists to claim that it is untested and dangerous, and to spin reasonable concerns about the vaccine into widespread, unfounded fears about its safety.
  • Second, if a vaccine does emerge, there is a good chance that leading health organizations like the Bill and Melinda Gates Foundation or the World Health Organization will have a hand in producing or distributing it. If that’s the case, anti-vaccine activists, who have been crusading against these groups for years, will have plenty of material stockpiled to try to discredit them. They are already taking aim at Mr. Gates with baseless conspiracy theories claiming that he created and is trying to profit from the virus. These theories will be amplified, and the attempts to discredit leading virus research efforts will intensify as the vaccine nears.
  • Third, if and when a Covid-19 vaccine is approved for widespread use, people may be required to take it before being allowed to fly on certain airlines, attend certain schools or enter certain businesses. That’s a good idea, public health-wise, but it would play into some of the worst fears of the anti-vaccine movement.
  • Mandatory vaccination has been an especially potent talking point for anti-vaccine activists, some of whom have rebranded themselves “pro-choice” when it comes to vaccines. And years of battling states and school districts over mandatory vaccine policies have given them a playbook for creating a tangle of legal roadblocks and damaging publicity campaigns.
  • I wanted to understand if my fears about a vaccine-related information war were valid, so I reached out to Neil Johnson and Rhys Leahy, two researchers at George Washington University. On Wednesday, their study of the online anti-vaccine movement was published in the science journal Nature.
  • The study, which mapped the vaccine conversation on Facebook during the 2019 measles outbreak, found that there were nearly three times as many active anti-vaccination communities as pro-vaccination communities. In addition, they found that while pro-vaccine pages tended to have more followers, anti-vaccine pages were faster-growing.
  • “We expected to find a strong core of ‘vanilla’ science — people saying that vaccines are good for you — but that’s not what we found at all,” Mr. Johnson told me. “We found a real struggle online, where the public health establishment and its supporters are almost fighting in the wrong place.”
  • The researchers found that Facebook pages pushing accurate pro-vaccine information were mostly clustered in an insular group, while the anti-vaccine pages treated vaccine resistance as a kind of political campaign, and used different messages to reach different types of undecided “voters.” A page promoting holistic health remedies might start seeding doubts about vaccines among liberal yoga moms, while a page promoting resistance to government-mandated vaccines might appeal to conservatives and libertarians.
  • “Public health advocacy groups tend to be monolithic, sending one message” that vaccines are safe and effective, Ms. Leahy said. “The anti-vax movement is really diverse.”
  • There is some reason for hope. Recent surveys have suggested that most Americans would take a C19 vaccine if one were available today. Even politicians who have expressed skepticism about vaccines in the past are rooting for one that can prevent the disease. And some public health experts I spoke to said public pressure to end the pandemic and return to normal life might overpower anti-vaccine activism.
  • “People are seeing the toll of C19 all around,” said Kasisomayajula Viswanath, a professor of health communication at the Harvard School of Public Health. “My guess is that if there is a successful vaccine, especially in the absence of treatment, people may discount the anti-vaccine groups.”
  • But public acceptance of a C19 vaccine is far from a sure thing. And seeing platforms like Facebook and YouTube struggle to contain the spread of videos like “Plandemic” makes me worry that when the time comes to persuade billions of people to take a critical coronavirus vaccine, our public health officials and social media companies will be outgunned by a well-oiled anti-vaccine movement that has already polluted the air with misinformation and conspiracy theories.
  • We can prevent that, but only if we start laying the groundwork before it’s too late. Organizations like the Centers for Disease Control and Prevention and the W.H.O. need to understand the dynamics of online anti-vaccination communities and start waging a hearts-and-minds campaign to restore faith in the medical establishment while a vaccine is being developed. Social media companies need to take the threat of vaccine-related misinformation seriously and devote tremendous resources to stopping its spread. And those of us who believe in vaccines need to realize that we may not be in the majority for long and do everything we can to reach the people in our lives who might be susceptible to anti-vaccine propaganda.
  • To recover from this pandemic, we need to mobilize a pro-vaccine movement that is as devoted, as internet-savvy and as compelling as the anti-vaccine movement is for its adherents. We need to do it quickly, with all the creativity and urgency of the scientists who are developing the vaccine itself. Millions of lives and trillions of dollars in economic activity may depend not just on producing a vaccine, but on persuading people to accept it.

Source: Get Ready for a Covid-19 Vaccine Information War

E. Testing

1. NYU Study: Abbott’s rapid coronavirus test misses more than 48% of positive cases 

Key Points:
  • Abbott Labs’ rapid coronavirus diagnostic test, which is used by the White House, could be missing nearly half of positive cases, according to a new study from researchers at New York University, which describes the test as “unacceptable.”
  • When using samples collected with “dry nasal swabs,” the Abbott test missed more than 48% of positive cases, the study said. 
  • Abbott disputed the findings of the study, adding that it has distributed about 1.8 million of the tests and the reported false-negative rate is 0.02%.
Introduction
  • The study, which has not been peer-reviewed, found Abbott’s ID NOW test missed one-third (1/3) of samples collected with nasopharyngeal swabs that tested positive with a test from rival Cepheid. When using samples collected with “dry nasal swabs,” the Abbott test missed more than 48% of positive cases, the study said. Both nasopharyngeal swabs and dry nasal swabs are collected from the nostril, but the former is inserted much deeper into the nose.
  • The methodology and the study have not yet undergone critique from colleagues and have not been edited or published by an academic journal.
  • Abbott Labs refuted the study’s claims that its rapid coronavirus diagnostic test could be missing nearly half of positive cases.
  • The Abbott ID NOW test demonstrated 91% sensitivity and 100% specificity in a separate study conducted in Washington state, the company said in a series of tweets Wednesday evening. 
  • “While no test is perfect, Abbott’s ID NOW is delivering reliable results when and where they’re needed most,” the company said in its response. “The world needs a variety of tests in labs and at point of care, and as many as possible, if we are to help reduce the risk people have every single day of contracting the virus.”
  • Abbott said it has many questions for the authors of the New York University study authors. 
  • “We are reviewing the information in this non-peer reviewed study,” a spokesperson for the FDA told NBC News.
  • The urgency to ramp up coronavirus testing in the U.S. “has eased the usual scrutiny” applied by the FDA before the release of a new test, according to the authors of the study. The FDA has issued emergency use authorizations for multiple tests, including Abbott’s, which means the tests can be used “without the more rigorous scrutiny to which tests are normally subjected to prior to FDA approval,” according to the study.
  • Capacity to test broadly throughout the population will be key to quickly detecting and preventing pockets of outbreak as states reopen nonessential businesses and ease restrictions, officials say. Point-of-care test like Abbott’s, which can yield results in as little as five minutes, are crucial to the effort.
  • Abbott disputed the findings of the study, adding that it has distributed about 1.8 million of the tests and the reported false-negative rate is 0.02%.
  • “Once again, a study has been conducted using ID NOW in a manner that it’s not intended to be used. It’s unclear if the samples were tested correctly and we’re further evaluating these results,” Abbott spokeswoman Darcy Ross said in a statement. “The outcomes in this paper are inconsistent with any experience that we’ve had with this instrument.”
  • The Abbott test became less accurate as the viral load in each sample decreased, the study said.
  • “Based on our findings we could argue that the Abbott ID NOW detects samples with high viral load or possibly viable virus that could be of importance for transmission,” the study said. “But, the fact that it misses positive samples on patients being admitted to the hospital with clinical picture of C19 makes this technology unacceptable in our clinical setting.”
  • The Abbott test is more efficient and portable than standard C19 diagnostic tests, which often require samples to be shipped to a lab that has the necessary equipment to analyze the results. Abbott received emergency use authorization for the test on March 27.
  • Politicians and officials have called for proposals for new rapid, point-of-care testing technology to quickly ramp up the country’s capacity to test for the virus, which will be key in preventing a resurgence as states begin to reopen.
  • Several retailers, including Walgreens and CVS Health, that have opened drive-thru coronavirus testing sites currently use the Abbott test. 

Source: Abbott’s rapid coronavirus test misses positive cases, raising questions, NYU study finds

2. Coronavirus Test Shortages Trigger a New Strategy: Group Screening  

  • Unless there is widespread testing for C19, experts warn, cases will surge as governments reopen more businesses and public spaces. But there is still a woeful shortage of diagnostic tests for coronavirus infections, because of unprecedented demand for chemicals and supplies. The U.S., for instance, does hundreds of thousands of tests a day, but that number is still far short of the millions of daily assays recommended for a safe return to normal.
  • Now dozens of researchers in the U.S., Israel and Germany are pursuing a strategy to dramatically increase diagnostic capacity: group tests. By pooling samples from many people into a few groups and evaluating pools rather than individuals, the scientists think they can use fewer tests on more people. 
  • This approach could lead to the faster detection of individuals who are unwitting carriers of the disease and an ability to quickly clear others who have not been infected. The strategy has been used in the past to successfully detect cases of HIV, chlamydia, malaria and influenza, and was originally conceived during World War II to test thousands of military personnel for syphilis.
  • “As long as we have no vaccine, we can only stop the transmission of the virus by testing and isolation of people who are infected,” says Sandra Ciesek, director of the Geothe University Frankfurt’s Institute of Medical Virology in Germany. 
  • In mid-February, she was among the first to report that people with no symptoms could spread the virus. Since then, Ciesek has been working on a pooled testing technique to identify asymptomatic carriers. The approach “is trying to do more with the same number of tests,” says Tomer Hertz, a computational immunologist at Ben-Gurion University of the Negev in Israel, who is also developing a batch-testing strategy. There is a caveat, though: as the prevalence of the infection in a community goes up, the ability to save resources through group testing goes down.
  • Group testing is a numbers game. Let’s say you are examining 100 people, and one of them is positive. Normally you would do 100 diagnostic tests, searching for genetic material from the virus in each individual. But with group testing, you can divide those 100 people into five groups of 20. That gives you five pools with 20 samples, and you use one test per pool. If the first four sample pools test negative, you have eliminated 80 people with four tests. If the last pool tests positive, you retest each sample in that last pool individually to identify the one with the disease. In the end, you did 25 tests instead of 100.
  • That was the allure for Peter Iwen, director of the Nebraska Public Health Laboratory, which is using a pooled approach. In March Iwen was looking at an extreme shortage of testing chemicals. But it wasn’t clear that the U.S. Food and Drug Administration (FDA), which regulates this kind of diagnostic test, would allow pooled testing. He spent two weeks trying the technique before presenting data showing that it saved the lab time and ingredients to the governor of Nebraska and the FDA. Within three days, just before his supplies were about to run out, Iwen received a letter from the governor giving him “full authorization to explore and proceed with all reasonable measures to expand testing at this time.”
  • Later he received an e-mail from the FDA saying it would not object to pools of five samples. “We figured this was as close to an approval as one can get,” Iwen says. An FDA spokesperson told Scientific American that the agency is “open to a variety of novel testing ideas, such as specimen pooling, and encourages all test developers to reach out to us to discuss appropriate validation approaches.”
  • Many of the strategies under development employ computers and robotics to design the optimal number of pools or to streamline the process. Hertz and his colleagues have developed a twist that eliminates the need to test any sample twice. Rather than separating samples into distinct pools, they divide each sample among pools that overlap. For example, say you are testing those same 100 samples from before, one of which is positive. You then distribute those 100 samples, in various combinations, into 14 groups of 50. Each sample appears in six or seven different pools. 
  • With one positive case, a specific sequence of six pools should come up positive. By knowing which sample uniquely belongs to all six pools—for instance, patient 74 is the only one that appeared in pools 1, 2, 7, 9, 12 and 13—you can trace that positive result back to an exact individual without having to retest any samples. When there is more than one positive case in the mix, it gets more complicated, so the researchers designed a computer algorithm to identify all the carriers.
  • Hertz’s approach does have potential to make assays more efficient, says Allen Bateman, assistant director of the Wisconsin State Laboratory of Health’s Communicable Disease Division, where he oversees C19 testing. But Bateman warns that diluting each sample into large pools could make the actual test less sensitive by causing it to label some positive cases of the disease as negative. Such false negatives have plagued diagnostic tests for C19 since the start of the pandemic.
  • The biggest limitation of the batch approach, however it is done, has less to do with the test itself and more with the nature of the disease. Group testing works well as long as the prevalence of a pathogen remains low. But if there are too many positive cases in the tested specimens, most of the pools will come up positive and will have to be followed up with individual tests anyway. 
  • Hertz’s combinatorial approach works best when the prevalence of the disease in a community is no higher than 5%, with around 1% being ideal. More straightforward approaches, such as those employed by Iwen and CIesek, work when the prevalence is below 10%. In fact, the FDA’s message to Iwen stated that he could test pools as long as the positive test rate was below that percentage.
  • Right now it is uncertain how many positive cases are circulating in the U.S., which makes it difficult to figure out where pooled testing would be worthwhile. The country’s delayed rollout of C19 testing allowed the virus that causes the disease to spread for weeks undetected. In Wisconsin, Bateman says that between 10 to 30% of tests performed in his lab come back positive. But as curves flatten and even fall, labs in the U.S. and other countries see an opportunity for group testing to ensure people are virus-free before they return to factories, hospitals or school systems.
  • “If you’re testing in a relatively asymptomatic population, it could be a way to monitor whether a second wave is coming, conserve resources and increase capacity,” says Benjamin Pinsky, medical director of Stanford University’s Clinical Virology Laboratory. Pinsky, who employed group testing early in the outbreak to trace community transmission of C19 in the San Francisco Bay Area, says he recently thought about using the approach again when he began screening Stanford Health Care’s workforce. But he decided against it because his lab currently has the capacity to handle the 10,000 tests it performs a week.
  • Pooled samples might help countries contend with the three potential futures envisioned by epidemiologists: recurring small outbreaks; a second, even bigger wave of infections and deaths; or a persistent crisis. For example, Ciesek partnered with Michael Schmidt of the German Red Cross to employ the high-tech machines usually reserved for screening blood donations to perform C19 group testing on patients admitted to University Hospital Frankfurt in Germany. As a result, patients with heart conditions or other ailments who may have avoided the hospital for fear of contracting the virus could be screened and placed in non-COVID units. The researchers say political leaders are pushing to expand the screening to all hospitals in Germany as the economy reopens.
  • “We know that when person-to-person contacts go up, there is more risk, because the virus has not gone away,” Schmidt says. “It is still in Germany. It is still in the United States. I think that creates a difficult situation, and you need a good strategy to handle it.”

Source: Coronavirus Test Shortages Trigger a New Strategy: Group Screening

F. Concerns & Unknowns

1. Does C19 target the nervous system?  

  • For many people, a sudden loss of smell is the first sign that something’s wrong. “One gentleman said he realized it with hand sanitizer,” says Carol Yan, a rhinologist at the University of California, San Diego. “All of a sudden it was like water to him.” The loss of smell, or anosmia, is such a common symptom of C19 that the US Centers for Disease Control and Prevention recently added it to its official list.
  • The loss of smell (or taste) is one of many emerging hints that the SARS-CoV-2 virus may affect the nervous system. Physicians around the world have documented neurological symptoms in a significant fraction of C19 patients. Some patients have experienced headaches, dizziness and other relatively minor symptoms, while others have had more serious problems like confusion and impaired movement, and even seizures and strokes.
  • Such reports have been circulating on message boards used by physicians, and they are just now making their way into the peer-reviewed scientific literature. Nobody knows at this point how widespread neurological symptoms are, nor the extent to which they contribute to the overall clinical picture for C19.
  • Another huge unknown is whether SARS-CoV-2 can attack the nervous system directly by infecting neurons — as rabies and a number of other viruses do — or cause neurological symptoms indirectly, by triggering rampant inflammation or blood clotting. 
  • These are critical questions, says Samuel Pleasure, a neuroscientist and neurologist at the University of California, San Francisco. For a small number of patients, neurological symptoms seem to be the earliest or even the only indicator of infection. For others, lingering or post-infection neurological problems could complicate recovery. “We don’t know whether or not that’s going to be the case yet, but it’s an important unanswered question,” says Pleasure.
No-smell test
  • Reports of lost taste and smell — often in the absence of the kind of nasal congestion that interferes with olfaction with the common cold — have been circulating for months. In one of the first peer-reviewed journal articles on the subject, Yan and colleagues describe results from an online survey of 262 patients in the UCSD hospital system. Slightly more than two-thirds of those who tested positive for C19 experienced taste and smell deficits.
  • The deficits weren’t subtle, Yan says. “Most people went from like a ten to zero.” Fortunately, as patients get better, they seem to be regaining their sensory abilities, usually within a few weeks, the team reported April 12 in the International Forum of Allergy & Rhinology. 
  • In an April 22 letter to the Journal of the American Medical Association, physicians reported a similar prevalence of anosmia in C19–positive patients at a regional hospital in Treviso, Italy. For 12 percent of these patients, the loss of smell occurred prior to other symptoms. For 3 percent, it was the only symptom they ever experienced.
  • Such reports have prompted several medical associations for ear, nose and throat specialists to issue statements urging physicians to consider anosmia as a potential screening tool for C19 and to advise patients who experience a sudden loss of smell to consider self-isolating.
  • In theory, SARS-CoV-2 could get into the brain through several routes. The virus could enter the brain through the bloodstream if it can get past the cellular defense wall known as the blood-brain barrier. Or it could conceivably infect olfactory neurons in the nasal cavity or peripheral nerves elsewhere in the body and hitchhike into the brain along their axons. Scientists don’t yet know which, if any, of these routes the virus can take.
  • Yan speculates that the presence of anosmia could turn out to be a clue to how the disease might progress. She notes that most patients in her study had relatively mild cases of C19 — most were not hospitalized, and none required a ventilator to help them breathe. In contrast, other researchers have found a lower prevalence of anosmia among sicker patients. One possibility, Yan says, is that anosmia is more common in mild cases because the virus mostly stays in the nasal cavity. In more severe cases, it infiltrates the lungs, causing more dangerous respiratory symptoms but fewer sensory deficits. At this point it’s just a hypothesis, but it’s one she and her colleagues plan to investigate.
  • Preliminary evidence suggests that SARS-CoV-2 does not directly infect olfactory neurons, the odor-detecting cells at the top of the nasal cavity, at least by its usual route. In April, two RNA sequencing studies — one led by researchers at Harvard, another by a group in Switzerland — concluded that olfactory neurons do not make two key proteins, including the ACE2 receptor, used by the virus to break into cells. (The findings were posted before publication on the website bioRxiv and have not yet been peer-reviewed.)
  • However, neighboring support cells do appear to produce these proteins. The sudden loss of smell in C19 patients could result from the virus infecting these support cells and then either causing local inflammation or disrupting the cells’ role in maintaining the balance of ions that olfactory neurons need to function properly, says neuroscientist Sandeep Robert Datta, who led the Harvard study.
Other warning signs
  • Reports of other neurological symptoms in C19 patients have emerged from China, France and elsewhere. In one of the first studies, doctors in Wuhan, China, reported April 10 in JAMA Neurology that of 214 patients hospitalized there between mid-January and mid-February, slightly more than a third experienced neurological symptoms that ranged from dizziness and headache to (less commonly) impaired consciousness, movement difficulties and seizures.
  • In an April 15 letter to the New England Journal of Medicine, doctors in Strasbourg, France, reported an even higher prevalence of neurological symptoms in a group of patients there: 84 percent experienced symptoms that included “prominent agitation and confusion” and alterations to reflexes and muscle contractions that suggested neurological problems in the brain.
  • The role SARS-CoV-2 plays in such symptoms remains an open question, especially for sicker patients who are likely to have low oxygen levels or preexisting conditions that could cause the same symptoms, says Pleasure, who cowrote an editorial on the Chinese study. “The kinds of symptoms that were more common in the more severe patients could be happening in part because the patients are so sick, not because they have C19,” he says.
  • There were scattered reports of neurological problems with SARS and MERS, respiratory syndromes caused by coronaviruses related to the one causing the current pandemic, but the prevalence of such symptoms wasn’t well documented. There seem to be more such reports with C19, but that could be because so many more people have been affected in total, not necessarily that those symptoms occur in a higher proportion of patients, says Stanley Perlman, an infectious disease researcher at the University of Iowa Carver College of Medicine. More than four million people (and counting) have been infected in the current pandemic, compared with about 8,000 for SARS and 2,500 for MERS.
  • Some researchers have speculated that SARS-CoV-2 may invade the nervous system and suppress respiratory centers in the brain, contributing to the severity of breathing problems. So far there’s no direct evidence for that, but scientists say it’s not out of the question. 
  • Pierre Talbot, a virologist at the Armand-Frappier Santé Biotechnologie Research Centre near Montreal, has long argued that coronaviruses could be an underestimated threat to the nervous system. In experiments with mice and cultured human neurons, his group has found evidence that a human coronavirus called OC43, a frequent cause of the common cold, can travel from the respiratory tract to the nervous system. In 2016, the researchers reported finding the virus in brain tissue from an 11-month-old boy who died of encephalitis, or inflammation of the brain. Coronaviruses can do much more than cause respiratory diseases, Talbot says. “The neurological aspects of C19 are not surprising.”
  • In experiments with genetically engineered mice, Perlman and his colleagues previously found that SARS and MERS can infect olfactory neurons and travel along their axons to the brain’s olfactory bulb. From there, the viruses spread quickly throughout the brain. His lab plans to repeat those experiments with SARS-CoV-2, but he cautions that mouse experiments may not replicate what a virus does in people in real-world conditions. And the new virus may act differently — as suggested by the bioRxiv studies that showed that the virus likely can’t infect the human olfactory neurons using its usual tactics.
  • Many viruses, Perlman says, have evolved other ways of getting into the nervous system — including tricks for slipping past the guardian cells of the blood-brain barrier, which normally keep blood-borne pathogens out of the brain. It’s still far too early to know all that SARS-CoV-2 is capable of. “This virus is teaching us so much,” Perlman says. “I wouldn’t draw any conclusions.” Experiments that might help resolve the issue, such as tests on spinal fluid or autopsied brain tissue from C19 patients, have been delayed by safety concerns.
  • Loss of smell has been reported in many C19 patients. Inhaled air comes into contact with olfactory neurons at the top of the nasal cavity, raising the possibility that SARS-CoV-2 could infect the neurons and travel into the olfactory bulb, a part of the brain. But preliminary work suggests the virus may not be able to infect olfactory neurons. Instead, it may infect the adjacent supporting and stem cells in the olfactory epithelium.
  • Even if SARS-CoV-2 does not directly attack the nervous system, it could cause neurological problems indirectly. One way it could do this is through rampant inflammation known as a cytokine storm. In a case study published in Radiology, doctors in Detroit reported brain scan abnormalities indicative of a rare encephalopathy linked to cytokine storms in an airline worker in her mid-50s who tested positive for the virus. Another concern is reports of mysterious abnormalities in blood clotting in young and middle-aged C19 patients that may increase the risk of stroke.
  • Some secondary effects could take time to develop. In an April 17 letter to the New England Journal of Medicine, Italian doctors described five C19 patients who developed Guillain–Barré syndrome, a condition that starts with weakness and tingling in the extremities and can progress to more serious movement difficulties. Guillain–Barré syndrome occurs after infection, such as with Campylobacter bacteria, a frequent cause of food poisoning, when antibodies made by the immune system to fight the bacteria end up attacking the nervous system instead.
  • If the same thing happens with SARS-CoV-2, Pleasure says, doctors may see a wave of post-infection neurological conditions like Guillain–Barré in the months ahead. As with nearly everything related to C19, the full impact won’t be known for some time.

Source: Loss of smell, confusion, strokes: Does Covid-19 target the nervous system? 

2. Can 23andMe Shed Light On Why Some Die and Others Show No Symptoms?  

  • Some people die from C19, and others who are infected don’t even show symptoms. But scientists still don’t know why.
  • Now consumer genomics company 23andMe is going to offer free genetic tests to 10,000 people who’ve been hospitalized with the disease, hoping to turn up genetic factors that could point to an answer.
  • While it’s known that older people and those with health conditions such as diabetes are most at risk, there could be hidden genetic reasons why some young, previously healthy people are also dying.  
  • 23andMe operates a large gene database with more than 8 million customers, many of whom have agreed to let their data be used for research. The company has previously used consumer data to power searches for the genetic roots of insomnia, homosexuality, and other traits.  
  • In April the company, based in Sunnyvale, California, sent C19 questionnaires out to a swath of its members. So far, says a company spokesman, about 400,000 have enrolled, including 6,000 who say they have confirmed cases of the pandemic disease.
  • The 23andMe gene hunt will complement efforts from university researchers to obtain genetic profiles of C19 cases and pair them with detailed medical records, says Andrea Ganna, who coordinates the C19 Host Genetic Initiative. The international consortium is sharing genetic data on C19 cases from Italy, the UK, and the US and regularly making results public.
  • Scientists hope to find a gene that strongly influences, or even determines, how badly people are affected by the coronavirus. There are well-known examples of such genetic effects on other diseases: for example, sickle-cell genes confer resistance to malaria, and variants of other genes are known to protect people from HIV or to norovirus, an intestinal germ.
  • According to Ganna, however, an initial peek at the genes of 900 C19 cases turned up no significant genetic hits. His consortium is now preparing an analysis of twice as many cases, which could improve their chance of spotting an association.
  • “If we don’t find a really big signal in the next month or so, then I think genetics is not going to be of huge value in the management of the disease, like determining who you treat,” he says. “What is still very, very important is the biology, and understanding the biology through the genetics, and then with vaccination.”
  • In its first survey, 23andMe asked customers if they’d been diagnosed with C19 or not. However, the company is now trying to locate patients who were hospitalized and recovered, because their genes are more likely to hold important information. 
  • Researchers have already speculated that blood type could influence a person’s version of ACE-2, the protein the coronavirus uses to fuse with human cells and gain access to them. But preliminary findings have not yet been borne out by the larger gene hunts.
  • The gene search is part of the scientific effort to move to more targeted ways of managing the pandemic, which some are calling “precision epidemiology.” In addition to 23ndMe, the DNA testing company Ancestry said it had received 250,000 responses in its own C19 project.

Source: The secret to why some people get so sick from covid could lie in their genes

G. Technology vs. C19

1. Artificial intelligence systems aim to sniff out signs of outbreaks  

  • The international alarm about the C19 pandemic was sounded first not by a human, but by a computer. HealthMap, a website run by Boston Children’s Hospital, uses artificial intelligence (AI) to scan social media, news reports, internet search queries, and other information streams for signs of disease outbreaks. 
  • On 30 December 2019, the data-mining program spotted a news report of a new type of pneumonia in Wuhan, China. The one-line email bulletin noted that seven people were in critical condition and rated the urgency at three on a scale of five.
  • Humans weren’t far behind. Colleagues in Taiwan had already alerted Marjorie Pollack, a medical epidemiologist in New York City, to chatter on Weibo, a social media site in China, that reminded her of the 2003 outbreak of severe acute respiratory syndrome (SARS), which spread to dozens of countries and killed 774. “It fit all of the been there, done that déjà vu for SARS,” Pollack says. Less than 1 hour after the HealthMap alert, she posted a more detailed notice to the Program for Monitoring Emerging Diseases, a list server with 85,000 subscribers for which she is a deputy editor.
  • The early alarm from HeathMap underscores the potential of AI, or machine learning, to keep watch for contagion. As the C19 pandemic continues to spread around the globe, AI researchers are teaming with tech companies to build automated tracking systems that will mine vast amounts of data, from social media and traditional news, for signs of new outbreaks. AI is no substitute for traditional public health monitoring, cautions Matthew Biggerstaff, an epidemiologist with the U.S. Centers for Disease Control and Prevention (CDC). “This should be viewed as one tool in the toolbox,” he says. But it can fulfill a need, says Elad Yom-Tov, a computer scientist with Microsoft who has worked with public health officials in the United Kingdom. “There’s such a wealth of data, we will need some sort of tool to make sense of those data, and to me that tool is machine learning.”
  • Well before C19 hit, CDC began an annual competition to most accurately predict the severity and spread of influenza across the United States. The competition, started in 2013, receives dozens of entries each year; Biggerstaff says roughly half involve machine learning algorithms, which learn to spot correlations as they are “trained” on vast data sets. For example, Roni Rosenfeld, a computer scientist at Carnegie Mellon University, and colleagues have won the competition five times with algorithms that mine data on, among other things, Google searches, Twitter posts, Wikipedia page views, and visits to the CDC website.
  • Many of teams involved in the flu challenge have now pivoted to tracking C19. They are applying AI in two ways. It can strive to spot the first signs of a new disease or outbreak, just as HealthMap did. That requires the algorithms to look for poorly defined signals in a sea of noise, a challenge on which a well-trained human may still hold the upper hand, Pollack says.
  • AI can also be used to assess the current state of an epidemic—so-called now-casting. The Carnegie Mellon teams aims to now-cast C19 across the United States, using data collected through pop-up symptom surveys by Google and Facebook, Google search data, and other sources in order to predict local demand for intensive care beds and ventilators 4 weeks into the future, Rosenfeld says. “We’re trying to develop a tool for policymakers so that they can fine-tune their social distancing restrictions to not overwhelm their hospital resources.”
  • Although automated, AI systems are still labor intensive, notes Rozita Dara, a computer scientist at the University of Guelph who has tracked avian influenza and is turning to C19. “By the time you get to AI, it’s the easy part,” she says. To train a program to scan Twitter, for example, researchers must first feed it examples of relevant tweets, selected by weeding through Twitter for many hours, Dara says. AI may also struggle in a rapidly evolving pandemic, where correlations between online behavior and illness can shift, says Jeffrey Shaman, an epidemiologist at Columbia University.
  • AI has misfired before. From 2009 to 2015, Google ran an effort called Google Flu Trends (now part of HealthMap’s machinery) that mined search query data to track the prevalence of flu in the United States. At first the system did well, correctly predicting CDC tallies roughly 2 weeks ahead of time. However, from 2011 to 2013, it overestimated the prevalence of flu. That failure arose largely because researchers didn’t retrain the system as people’s search behavior evolved, Yom-Tov says, and it misinterpreted searches for news reports about the flu as signs of infection.
  • “I don’t think it’s an inherent problem with the field,” Yom-Tov adds. “It’s something that we’ve learned from.” In fact, he and colleagues from University College London recently posted a paper to the arXiv preprint server showing they could correct for that media-related bias.
  • Officials in nations that struggle to provide adequate testing for the new coronavirus, such as the United States, might be tempted to use automated surveillance systems instead. Biggerstaff says that would be a mistake: “I don’t think this can replace testing in any way.” In particular, he says, when the flu re-emerges this fall, direct testing will be necessary to distinguish outbreaks of influenza from C19. But AI might help policymakers direct more testing to hot spots. “The hope is that you would actually have the two working together,” says John Brownstein, an epidemiologist at Boston Children’s who co-founded HealthMap in 2006.
  • Some researchers question whether AI systems will be ready in time to help with the C19 pandemic. “AI will not be as useful for COVID as it is for the next pandemic,” says Dara, who expects it will take about 6 months to develop her system for tracking the disease. Still, data mining and machine learning in epidemiology seem here to stay. Pollack, who sounded the alarm about C19 the old-fashioned way, says she, too, is working on an AI program to help scan Twitter for mentions of the disease.

Source: Artificial intelligence systems aim to sniff out signs of outbreaks

H. Collateral Damage

1. C19-related service disruptions could cause hundreds of thousands of extra deaths from HIV  

  • A modelling group convened by the World Health Organization and UNAIDS has estimated that if efforts are not made to mitigate and overcome interruptions in health services and supplies during the C19 pandemic, a six-month disruption of antiretroviral therapy could lead to more than 500,000 extra deaths from AIDS-related illnesses, including from tuberculosis, in sub-Saharan Africa in 2020–2021. In 2018, an estimated 470,000 people died of AIDS-related deaths in the region.
  • There are many different reasons that could cause services to be interrupted—this modelling exercise makes it clear that communities and partners need to take action now as the impact of a six-month disruption of antiretroviral therapy could effectively set the clock on AIDS-related deaths back to 2008, when more than 950,000 AIDS-related deaths were observed in the region. And people would continue to die from the disruption in large numbers for at least another five years, with an annual average excess in deaths of 40% over the next half a decade. In addition, HIV service disruptions could also have some impact on HIV incidence in the next year.
  • “The terrible prospect of half a million more people in Africa dying of AIDS-related illnesses is like stepping back into history,” said Dr Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization.
  • “We must read this as a wake-up call to countries to identify ways to sustain all vital health services. For HIV, some countries are already taking important steps, for example ensuring that people can collect bulk packs of treatment, and other essential commodities, including self-testing kits, from drop-off points, which relieves pressure on health services and the health workforce. We must also ensure that global supplies of tests and treatments continue to flow to the countries that need them,” added Dr Tedros.
  • In sub-Saharan Africa, an estimated 25.7 million people were living with HIV and 16.4 million (64%) were taking antiretroviral therapy in 2018. Those people now risk having their treatment interrupted because HIV services are closed or are unable to supply antiretroviral therapy because of disruptions to the supply chain or because services simply become overwhelmed due to competing needs to support the C19 response.
  • “The C19 pandemic must not be an excuse to divert investment from HIV,” said Winnie Byanyima, Executive Director of UNAIDS. “There is a risk that the hard-earned gains of the AIDS response will be sacrificed to the fight against C19, but the right to health means that no one disease should be fought at the expense of the other.”
  • When treatment is adhered to, a person’s HIV viral load drops to an undetectable level, keeping that person healthy and preventing onward transmission of the virus. When a person is unable to take antiretroviral therapy regularly, the viral load increases, impacting the person’s health, which can ultimately lead to death. Even relatively short-term interruptions to treatment can have a significant negative impact on a person’s health and potential to transmit HIV.
  • Shorter disruptions of 3 months would see a reduced but still significant impact on HIV deaths. More sporadic interruptions of antiretroviral therapy supply would lead to sporadic adherence to treatment, leading to the spread of HIV drug resistance, with long-term consequences for future treatment success in the region.
  • Disrupted services could also reverse gains made in preventing mother-to-child transmission of HIV. Since 2010, new HIV infections among children in sub-Saharan Africa have declined by 43%, from 250,000 in 2010 to 140,000 in 2018, owing to the high coverage of HIV services for mothers and their children in the region. Curtailment of these services by C19 for six months could see new child HIV infections rise drastically, by as much as 37% in Mozambique, 78% in Malawi, 78% in Zimbabwe and 104% in Uganda.
  • Other significant effects of the C19 pandemic on the AIDS response in sub-Saharan Africa that could lead to additional mortality include reduced quality clinical care owing to health facilities becoming overstretched and a suspension of viral load testing, reduced adherence counselling and drug regimen switches. Each model also considered the extent to which a disruption to prevention services, including suspension of voluntary medical male circumcision, interruption of condom availability and suspension of HIV testing, would impact HIV incidence in the region.
  • The research highlights the need for urgent efforts to ensure the continuity of HIV prevention and treatment services in order to avert excess HIV-related deaths and to prevent increases in HIV incidence during the C19 pandemic. It will be important for countries to prioritize shoring up supply chains and ensuring that people already on treatment are able to stay on treatment, including by adopting or reinforcing policies such as multi-month dispensing of antiretroviral therapy in order to reduce requirements to access health-care facilities for routine maintenance, reducing the burden on overwhelmed health-care systems.
  • “Every death is a tragedy,” added Ms Byanyima. “We cannot sit by and allow hundreds of thousands of people, many of them young, to die needless deaths. I urge governments to ensure that every man, women and child living with HIV gets regular supplies of antiretroviral therapy—something that’s literally a life-saver.”

Source:  The cost of inaction: COVID-19-related service disruptions could cause hundreds of thousands of extra deaths from HIV

I. Projections & Our (Possible) Future

1. Coronavirus Models Are Nearing Consensus, but Reopening Could Throw Them Off Again  

  • There is growing consensus among modelers estimating the number of cases and deaths from the novel coronavirus in the next few weeks.
  • But this convergence of estimates — 31,000 to 42,000 additional deaths through mid-June for roughly 120,000 total deaths in the United States — comes just as shifts in public policy are likely to create new uncertainty about the path of the pandemic after that.
  • Three weeks ago, predictions from five popular models were widely divergent. Now, their outputs look far more similar.
  • A model from the University of Washington, once frequently cited by the White House for its relatively optimistic mortality estimates, has been retooled, and its expected death totals have risen. Others that had anticipated very high death tolls, from Imperial College London and Columbia University, have been adjusted downward. Our charts here show past outputs from the five models in addition to the past and new predictions of two more, from the University of Texas at Austin and from the independent data scientist Youyang Gu. [Note: The charts can be seen at NY Times Coronavirus Model
  • The model from Columbia, which assumes that people will loosen their social distancing behavior soon, estimates roughly 1,800 daily deaths in four weeks, the highest of the group making four-week forecasts. The lowest estimate, from the University of Texas, projects daily deaths will drop to less than 700 by June 1. These are large differences, but far smaller than what we saw just a few weeks ago.
  • Scientists who build models say they find it more useful to look at an ensemble of serious models at once than to rely on one.
  • “We know there is no perfect model,” said Lauren Ancel Meyers, a professor of integrative biology at the University of Texas, who recommended the ensemble approach as a good way to understand the range of likely outcomes.
  • The models depicted in our series of charts use slightly different methods. Some rely on classic epidemiology models; others incorporate methods from spatial statistics; some use data about mobility from cellphone records; one uses experiences with the disease overseas as a possible template for the American experience.
  • The researchers say that they are getting better at understanding the dynamics of the pandemic as Americans largely shelter in place, and that improved knowledge may explain the growing consensus of the models. The near-term future of the pandemic is also a little easier to imagine, with deaths flattening instead of growing rapidly. There may be some peer pressure, too. Nicholas Reich, a biostatistician at the University of Massachusetts who has led a project to standardize and compare model outputs, said he worried about the temptation to “herd” outputs. “Probably no one wants to have the really super-outlying low model or the super-outlying high model,” he said.
  • As the past record of the models depicted above shows, some of the older predictions have missed by quite a bit.
  • Dylan George, who worked on Ebola response in the Obama White House’s office of science and technology, and is now a vice president at the technology investment firm In-Q-Tel, said substantially improving the quality of disease modeling might require government spending. He compared the epidemic forecasts to weather forecasts, which were primitive in the last century but have been improved through government investment to become more useful for planning daily life. Weather forecasts also save lives through better predictions of events like hurricanes.
  • “These are great people who have spent their careers trying to figure these things out,” he said of the academic disease modelers, but he added that their work was not enough. “If a hurricane were coming barreling down on Florida, we wouldn’t randomly ask a bunch of academics to help us track the hurricane. We would have people who, this is their day job.”
  • Politicians have begun easing restrictions on public gatherings and business activities, and those changes are likely to lead to changes in behavior and to increased transmission of the disease. By how much is still unclear. “There’s a lot more uncertainty because the system is changing under our feet,” said Ms. Meyers, who leads the team behind the University of Texas model, which incorporates cellphone data about how much people are moving and interacting.
  • Ms. Meyers said changes in behavior were likely to begin showing up as changes in the number of deaths in three or four weeks, just at the edge of the recent predictions.

Source:  Coronavirus Models Are Nearing Consensus, but Reopening Could Throw Them Off Again

J. Origins of the Coronavirus

1. Scientists: ‘Exactly zero’ evidence C19 came from a lab  

  • Since the C19 pandemic began, the Internet has been teeming with provocative conspiracy theories that the novel coronavirus was (1) created in a Wuhan, China, lab and deployed as a bioweapon or (2) derived from bats, grown on tissue culture, intentionally or accidentally transmitted to a researcher, and released into the community.
  • Politicians have touted these theories in an attempt to blame China for the pandemic, and a discredited US scientist recently released a book and now-banned video claiming that wealthy people deliberately spread C19 to boost vaccination rates. And late last week, an unsubstantiated NBC News report on cell phone location data suggested that the Wuhan lab temporarily shut down after a “hazardous event” in October.
  • Even Kristian Andersen, PhD, a professor in the Department of Immunology and Microbiology at Scripps Research Institute in La Jolla, California, and lead author of a research letter published Mar 17 in Nature Medicine on the origins of the virus, first thought that C19 was just as likely to have been accidentally released from a lab as it was to have come from nature.
  • But that was before he learned more about C19 and related coronaviruses, which have features already seen in nature. “There are lots of data and lots of evidence, as well as previous examples of this coming from nature,” he said. “We have exactly zero evidence or data of this having any connection to a lab.”
  • And while Andersen, like other prominent virologists, says that he can’t completely rule out the possibility that the virus came from a lab, the odds of that happening are very small. He says the new coronavirus clearly originated in nature, “no question about it by now.”
Conspiracy theory #1: Chinese bioweapon
  • C19 is sufficiently unlike other viruses to have been created from them, and making a virus in the lab from scratch would be “virtually impossible,” said Stanley Perlman, MD, PhD, professor of microbiology and immunology and pediatric infectious diseases at the University of Iowa in Iowa City. “I don’t think we know enough about coronaviruses—or any virus—to be able to deliberately make a virus for release,” he said.
  • James Le Duc, PhD, professor of microbiology and immunology and director of the Galveston National Laboratory at the University of Texas Medical Branch in Galveston, said that engineering C19 “would have taken an incredible amount of ingenuity. People’s imaginations are running wild.”
  • Andersen said that the virus’s receptor binding domain, which makes it an efficient human pathogen, is also found in coronaviruses in pangolins, scaly anteaters proposed as an intermediary host between bats and humans. “It’s something that’s fully natural, so it’s not something that happens in tissue culture,” he said.
  • Angela Rasmussen, PhD, an associate research scientist in the Center for Infection and Immunity at Columbia University in New York City, said computer modeling suggests that the receptor-binding domain of the spike protein in SARS-CoV-2, the virus that causes C19, is suboptimal, “meaning that someone designing an optimal receptor-binding domain sequence probably would not ‘engineer’ the sequence that evolved in SARS-CoV-2,” she said.
  • “Furthermore, there are no genetic similarities with other virus backbones used in any of the known reverse genetics systems for betacoronaviruses. This suggests that this virus was not engineered.”
  • Another C19 feature, its furin cleavage site, which allows the virus to infect human cells, diminishes in tissue culture, Andersen said. “I think it could probably still infect people, I just think much less efficiently,” he added.
  • Furthermore, he questions why anyone would go through the work of creating a new virus when they could simply take an existing virulent pathogen like the SARS (severe acute respiratory syndrome) or MERS (Middle East respiratory syndrome) coronaviruses and make them even worse, as all bioweapons programs so far have done.
  • “It doesn’t make any sense to make a new virus that you don’t know can cause disease in humans and try to create a bioweapon out of it,” Andersen said. “That would be a really bad bioweapons person.”
Conspiracy theory #2: Lab release of natural virus
  • For many years around the world, scientists have studied bat coronaviruses by capturing bats in caves and isolating and growing in tissue culture the coronaviruses that they carry to see if they can infect human cells.
  • Called gain-of-function research, these studies improve a pathogen’s ability to cause disease so that researchers can characterize its interactions with humans, allowing evaluation of its potential to cause a pandemic and informing public health, preparedness, and development of potential therapeutics and vaccines.
  • Shi Zhengli, PhD, director of the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology, a biosafety level 4 (BSL-4) lab in China relatively close (25 to 35 kilometers [15 to 22 miles]) to the Wuhan live-animal market at the epicenter of China’s outbreak, has extensively published the genetic sequences of isolates from the bat coronaviruses she studies.
  • None of them match those of C19, Andersen said, something Shi herself confirmed in a recent interview in Scientific American. “If she would have published a sequence for the virus and then this pops up, then we would have known it came from the lab,” Andersen said. “There’s no evidence for this, but there is plenty of evidence against it.”
  • Le Duc said that Shi’s work on bat coronaviruses has shown that “these viruses exist in nature, and some of them have characteristics that would allow them to be transmissible among humans. The fact that we’re seeing it today is not a surprise to folks that have been working in this field.”
  • And although “certainly, accidents happen in laboratories,” the high level of biocontainment at Shi’s lab makes it unlikely, he said. BSL-4 labs have the most stringent biosafety protocols, which may include airflow systems, sealed containers, positive-pressure personal protective equipment (PPE), extensive training, and highly controlled access to the building.
  • Having attended conferences at which Shi has spoken about her work, Le Duc said she is a highly reputable scientist. “She’s always been extremely open, transparent, and collaborative, and I have no reason to doubt that she’s telling the truth,” he said.
  • Plus, Andersen said the likelihood of a researcher becoming unknowingly infected with the coronavirus while wearing full PPE and then going to the Wuhan market is “fleeting compared to the alternative hypothesis, which is that we as humans, because we live amongst animals carrying these viruses—bats, but also many other intermediate hosts—and, of course, we don’t go around wearing PPE, we naturally get into contact with these viruses all the time.”
  • Yet a virus with pandemic potential is exceedingly rare, he said. “If these viruses were really frequent, we would all be dead by coronaviruses by now,” Andersen said. “We would have coronavirus pandemics all the time. We don’t, but they do pop up every 10 years or so, on average.”
  • Rasmussen said that the most plausible scenario is a “natural zoonotic spillover,” adding that serology studies have shown that some people in China living near bat caves have antibodies against bat SARS-like coronaviruses in their blood, “suggesting that people are exposed to related viruses in the course of their daily lives, so it’s not implausible that SARS-CoV-2 emerged in humans through a chance encounter between a human and a wild bat or some other animal.”
Doubts about ever pinpointing origin
  • Perlman said scientists may never be able to track down the origins of the virus or its intermediary host. “I think it’s really an important issue, figuring out where the virus comes from, but it’s just a hard business finding it,” he said.
  • It’s human nature, he said, to want to blame someone for a natural but catastrophic event like the pandemic. “Something bad happens, and someone has to be responsible for it,” he said.
  • Even so, Perlman decried the use of unproven origin theories to push agendas. “I think it’s been used way too much as a political issue,” he said. “This politicization of this is very unfortunate.”
  • But Andersen said he thinks theories do deserve exploration, even if to ultimately refute them. “It’s important that we don’t dismiss them out of hand,” he said. “We need to look at the data and say ‘what does the data tell us?’ And the data in this case are very strong.”

[Note: Even if all of the information and facts presented are true, which in our view should not be assumed, the evidence is circumstantial.  While the conclusions reached by the author can be reasonably inferred from the circumstantial evidence discussed in the story, the evidence by itself proves nothing.  On the flip side, we have not yet seen compelling evidence that the coronavirus originated or escaped from a Chinese lab.  So, for what it’s worth, in our view the origin of the coronavirus remains an open issue, although we believe that if the virus originated from a Wuhan lab, it is more likely to have been an inadvertent release as part of research rather than from a bioweapon program.]  

Source: Scientists: ‘Exactly zero’ evidence COVID-19 came from a lab

John Hopkins Daily COVID-19 Updates

May 13, 2020

EPI UPDATE The WHO COVID-19 Situation Report for May 12 reports 4.09 million confirmed cases (82,591 new) and 283,153 deaths (4,261 new). The global total could potentially reach 300,000 deaths by later this week.

The majority of countries are currently exhibiting doubling times of more than 10 days. Compared to the end of March—when most countries’ epidemics were doubling faster than 8 days—this is an encouraging sign. A number of countries in Africa, however, are doubling faster. Burundi, the Central African Republic, Gabon, Guinea-Bissau, South Sudan, Sudan, Togo, and Zambia are all currently doubling faster than 10 days. The combination of low testing and surveillance capacity (and variation between countries), inconsistent reporting, and relatively low reported incidence in many countries results in highly dynamic doubling times. At the continent level, Africa’s COVID-19 epidemic is doubling approximately every 10-15 days.

Several countries have recently reported concerning per capita COVID-19 incidence. Bahrain, Belarus, Chile, Kuwait, Russia, the United Arab Emirates are all reporting more than 75 new cases per million population each day. For reference, the United States has consistently reported 60-100 new cases per million since late March, and the global average is approximately 10 new cases per million population. Additionally, all but Singapore have increased over the past several weeks. Other notable countries in terms of daily per capita incidence include Peru (71.2), the United States (60.9), Saudi Arabia (55.4), and the United Kingdom (55.0). Of these countries, Peru and Saudi Arabia have been increasing since late March.

Russia reported more than 10,000 new cases, continuing its recent trend of elevated incidence. Russia’s daily incidence is approximately twice what it was in late April. Russia will likely reach 250,000 cases tomorrow. India reported 3,525 new cases, continuing its recent trend of elevated daily incidence. Tamil Nadu state, where a large outbreak has been linked to one of Asia’s largest markets, reported 716 new cases. The number of active cases in Tamil Nadu doubled over the previous 6 days, and Tamil Nadu now reports the second highest number of active cases among all Indian states. Singapore reported 675 new cases, including 671 (99.4%) among residents of migrant worker dormitories. Outbreaks in migrant worker dormitories continue to drive Singapore’s growing COVID-19 epidemic. Singapore estimates that 7.12% of the total population across all migrant worker dormitories are confirmed cases, compared to only 0.03% of the general public population. Of the 25,346 total COVID-19 cases reported in Singapore, 23,008 (90.8%) are among residents of migrant worker dormitories.

United States

The US CDC reported 1.34 million total cases (18,106 new) and 80,820 deaths (1,064 new). The daily incidence is the lowest since March 27. Based on the pattern from previous weeks, we expect the incidence to be higher over the next several days due to reporting delays over the weekend. Nonetheless, today’s report is still lower than previous Tuesday updates—19,138 new cases reported last Tuesday and 23,371 new cases the week before. The United States could potentially reach 1.5 million cases by Tuesday next week. In total, 7 states (increase of 1) reported more than 40,000 cases, including New York with more than 300,000; New Jersey with more than 125,000; and Illinois and Massachusetts with more than 75,000. Additionally, 35 states (no change), plus Guam, are reporting widespread community transmission.

New York state and New York City both reported their fifth consecutive day of decreasing daily incidence and their lowest daily incidence since March 17. While New York City continues to represent the majority of cases in the state, incidence outside of New York City is declining as well.

The New York Times continues to track state-level COVID-19 incidence, with a focus on state policies regarding social distancing. The Johns Hopkins CSSE dashboard is reporting 1.38 million US cases and 82,806 deaths as of 12:30pm on May 13.

SINGAPORE OUTBREAK Singapore has reported an average of 700 new cases per day across all dormitories housing migrant workers—compared to 8 new cases per day among the broader public. In response to these numbers, Singapore’s Ministry of Health has implemented a mass testing strategy at these dormitories, using a combination of PCR and serological tests. Singapore is currently testing more than 3,000 migrant workers per day. With the aggressive testing strategy, health authorities expect reported incidence to remain high for some time as new cases are found, and will then decrease as the outbreaks are brought under control through case identification and isolation.

In addition to addressing transmission among migrant workers, health authorities are beginning to develop creative ways to encourage physical distancing. A pilot project will utilize the Boston Dynamics robot dog “Spot” to patrol public parks and broadcast pre-recorded messages reminding residents to adhere to physical distancing guidance. Spot will also reportedly be capable of estimating the number of individuals in the park, but it will not use facial recognition or other systems to identify or track individual people. If the pilot goes well, authorities will consider expanding the program to busier park hours and to more locations. Spot is also being used to deliver medication to patients in designated isolation facilities. 

mRNA VACCINE DEVELOPMENT Biotechnology company Moderna received US FDA “Fast Track” designation for the development of its mRNA vaccine against SARS-CoV-2. The Fast Track program is designed to facilitate expedited review of therapeutics for life-threatening conditions. Messenger RNA (mRNA) technology uses natural cellular processes to produce proteins designed to increase immune defenses against the pathogen for which the proteins are designed. Moderna’s mRNA-1273 vaccine candidate is designed to mimic the SARS-CoV-2 spike protein that will hopefully produce a rapid and targeted immune response against future infection. The vaccine has already undergone a Phase 1 clinical trial led by the National Institute for Allergy and Infectious Diseases, and results are expected soon. Moderna is currently preparing protocols for Phase 2 and 3 clinical trials, tentatively scheduled to begin this summer.

PROTECTIVE IMMUNITY Serological tests are a key component of testing strategies to provide information on prior infections with SARS-CoV-2. Rapid diagnostic tests (RDTs) and ELISA tests can detect antibodies specific to SARS-CoV-2 in a matter of minutes or hours, respectively. A major drawback of these tests is that they cannot determine whether the detected antibodies provide protection against future infection. In order to answer this question, results from RDTs and ELISA tests must be correlated against neutralization assays, the gold standard for determining protective immunity. To fill this gap, Vyriad, in partnership with Regeneron, developed a neutralizing antibody test that can be performed at a lower biosafety level in CLIA-certified laboratories. Neutralization assays usually must be performed at high biosafety levels due to the need to work with live pathogens. The results for these tests typically take 1 week, so a safer and more rapid approach is needed to determine protective immunity for recovered COVID-19 patients. Vyriad is currently applying for FDA Emergency Use Authorization for this test.  

REOPENING WASHINGTON STATE BUSINESSES As Washington state continues its process of relaxing social distancing measures, Governor Jay Inslee released guidance for various sectors under the state’s “Safe Start” plan. Under Phase 2 of the state’s plan, retail stores must remain below 30% occupancy and identify and reduce choke points where customers could become clustered in order to maintain the recommended physical distancing. Restaurants must maintain below 50% occupancy for both indoor and outdoor seating and must close off any bar seating. Additional cleaning and disinfection guidelines are provided as well. This guidance also outlines provisions for employee safety and facility hygiene as businesses, including retail stores and restaurants, begin to resume in-person operations. 

BROADWAY THEATERS REMAIN CLOSED Broadway theaters in New York City will remain closed for the foreseeable future, with no reopening date yet set. The Broadway League announced that refunds and exchanges will be offered for any tickets for performances through September 6. New York and New Jersey remain hot spots for COVID-19 cases, and many businesses are shuttered, but the New York City economy will likely be negatively impacted from Broadway theater closures. According to the Broadway League, Broadway business contributed approximately $14.7 billion to the city’s economy in 2018-19 and accounts for more than 100,000 jobs, including show cast, crew, and theater operators.

SOCIAL DISTANCING & VIOLENCE Reports of violence associated with physical distancing policies continue, in the United States and elsewhere, as countries develop and implement plans to ease these restrictions while mitigating the risk of a resurgence in transmission. In addition to high-profile protests over state social distancing requirements in the US, there have also been a number of incidents involving law enforcement or members of the public violating or trying to enforce social distancing measures. One major point of contention as state and local governments adjust social distancing measures is the use of face masks or coverings. Face coverings are mandatory in some parts of the country but not others, and some governments have maintained requirements for mask use in public as they ease other restrictions. In some states where mask use is not mandatory, individual businesses are permitted to set their own requirements, which can result in variations within the same community. Confrontations between employees and patrons over mask requirements have resulted in multiple physical altercations and at least one shooting in the United States. Other incidents involving violence related to enforcing physical distancing have been reported in other countries as well, including the United Kingdom and Germany.

UK ECONOMIC IMPACT The UK Office for National Statistics published economic data for the first quarter of 2020, including a 2% decrease in the gross domestic product. The first quarter only included 1 week of “lockdown,” and the second quarter is expected to be worse due to the prolonged implementation of national physical distancing measures. Like the United States and many other countries, the United Kingdom is forecasting a severe recession as a result of the COVID-19 pandemic. The Bank of England reportedly projected that the UK economy could shrink by 30% for the first half of 2020, followed by a recovery in the second half of the year—potentially resulting in a 14% decrease over the course of the year. The UK’s COVID-19 epidemic has also had major negative effects on unemployment. The United Kingdom is beginning to ease some national physical distancing policies this week, but it remains to be seen how much and how quickly these changes will impact the UK economy.

COVID-19 MORTALITY MODELS Several high-profile models of expected COVID-19 deaths used by government officials appear to be converging on similar mortality projections for the next several months. Researchers at the University of Massachusetts Amherst evaluated these models and merged them into a single “ensemble” model based on a technique typically used for annual seasonal influenza models—which has demonstrated the utility of ensemble models. As more data become available, the various models appear to be coming into closer agreement. Notably, the difference between the highest and lowest COVID-19 mortality projections decreased from 36,000 deaths to 17,000 deaths over the past 2 weeks. The ensemble model projects approximately 110,000 cumulative COVID-19 deaths in the United States by June 6, but this total “will unquestionably rise much higher” after that point.

US SENATE COVID-19 HEARING Yesterday, the US Senate Committee on Health, Education, Labor, and Pensions held a hearing with several senior officials from the US government’s COVID-19 response. Dr. Anthony Fauci (NIAID), Dr. Robert Redfield (CDC), Admiral Brett Giroir (HHS), and Dr. Stephen Hahn (FDA) offered testimony on the US COVID-19 response and the epidemic’s trajectory, with a particular focus on states’ efforts to begin easing physical distancing restrictions. The experts addressed a broad scope of topics, including the potential for increased transmission as states relax stay at home measures, the timeline for vaccine availability, the distribution of remdesivir, and the US COVID-19 death toll.

DOWNSTREAM IMPACT As we have covered previously, the effects of the COVID-19 pandemic reach far beyond the immediate illness and death associated with the disease. The WHO and UNAIDS jointly warned about the impacts of disruptions to the supply chain and health services on excess deaths from HIV/AIDS, particularly in the sub-Saharan African region. A modeling group convened by WHO and UNAIDS estimated that a 6-month disruption in antiretroviral therapy could result in 500,000 excess deaths from AIDS-related illnesses in sub-Saharan Africa in the coming year. Disrupted services could reverse hard-fought gains in the region, where 25.7 million people are living with HIV/AIDS. In response to this study, Dr. Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization, called on countries to maintain critical health services and support for vulnerable countries and populations in the midst of the COVID-19 pandemic. 

TANZANIA Since late April, COVID-19 reporting from Tanzania has been uneven. Tanzania reported 180 new cases on April 30, corresponding to a 60% increase in the national total, and another 29 new cases on May 8, but nothing else to date. Today, the US Embassy in Dar es Salaam issued a Health Alert that highlighted the COVID-19 risk in Tanzania. The alert notes that Tanzania has not consistently reported COVID-19 data and that “all evidence points to exponential growth of the epidemic in…Tanzania.” The alert also states that “many hospitals in Dar es Salaam have been overwhelmed in recent weeks” and that “the risk of contracting COVID-19 in Dar es Salaam is extremely high.”

Tanzanian President John Magufuli has denied reports of increased incidence. According to several reports, President Magufuli recently accused public health laboratories of reporting falsified positive test results in an attempt to make the situation appear worse. He claimed that he secretly submitted specimens from a goat, sheep, bird, and papaya to Tanzania’s National Laboratory and that the tests were positive, providing evidence that the laboratory results cannot be trusted. Additionally, President Magufli suspended the National Laboratory director in order to conduct an investigation. Several reports also claim that Tanzania is withholding reports of COVID-19 deaths. Tanzania has officially reported only 21 total deaths, but there is concern that the actual total could be much higher.

NEW US HOUSE COVID-19 BILL Democrats in the US House of Representatives introduced a new economic stimulus bill to support essential workers, including frontline healthcare professionals and first responders. The bill—called the Health and Economic Recovery Omnibus Emergency Solutions Act (HEROES Act)—would provide an estimated US$3 trillion in funding to individuals and state, local, and tribal governments. In addition to funding for stimulus checks, supplemental unemployment benefits, student loan forgiveness, small businesses, and healthcare, the new bill includes a number of other provisions. Notably, the HEROES Act would provide supplemental pay for “essential frontline workers”—$25,000 each through the end of 2020—and a $15,000 recruitment incentive to facilitate expanding the healthcare workforce. The House of Representatives is expected to vote on the bill by Friday

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