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Dennis OConnor

What Went Wrong with Coronavirus Testing in the U.S. | The New Yorker - 0 views

  • n February 5th, sixteen days after a Seattle resident who had visited relatives in Wuhan, China, was diagnosed as having the first confirmed case of COVID-19 in the United States, the Centers for Disease Control, in Atlanta, began sending diagnostic tests to a network of about a hundred state, city, and county public-health laboratories⁠. Up to that point, all testing for COVID-19 in the U.S. had been done at the C.D.C.; of some five hundred suspected cases⁠ tested at the Centers, twelve had confirmed positive. The new test kits would allow about fifty thousand patients to be tested, and they would also make testing much faster, as patient specimens would no longer have to be sent to Atlanta to be evaluated.
  • Before a state or local lab could use the C.D.C.-developed tests on actual patients
  • verification
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  • larger number, about thirty-six of them, received inconclusive⁠ results from one of the reagents.
  • Another five,
  • had problems with two reagents
  • On February 8th
  • e cascading effects that they’ve had on the country’s COVID-19 preparations suggest a much larger problem with the way the United States has structured its pandemic response.
  • the verification problems were “part of the normal procedures⁠.” In the meantime, she said, until new reagents could be manufactured, all COVID-19 testing in the United States would continue to take place exclusively at the C.D.C⁠.
  • The public-health-laboratory network was never intended to provide widespread testing in the event of a pandemic.
  • the three-week delay caused by the C.D.C.’s failure to get working test kits into the hands of the public-health labs came at a crucial time.
  • The void created by the C.D.C.’s faulty tests made it impossible for public-health authorities to get an accurate picture of how far and how fast the disease was spreadin
  • In hotspots like Seattle, and probably elsewhere, COVID-19 spread undetected for several weeks, which in turn only multiplied the need for more tests.
  • The problem was that containment was not done very well.
  • we’re looking at exponential growth, and we need to figure out how to meet an exponential demand.”
  • Yet flexibility was not what Jerome and his lab found when they tried to get an E.U.A. for their COVID-19 test.
  • problem was exacerbated by a President who has simultaneously underplayed the severity of the outbreak and overpromised the means available to fight it
  • problems with COVID-19 testing in the United States have obscured
  • several labs reported their problems to the C.D.C. In a briefing a few days later,
  • Chinese scientists uploaded a copy of the virus’s genome to an online repository⁠, and virologists around the world set to work to develop diagnostic tests for the new disease
  • January 21st, a team in Berlin, led by Christian Drosten, one of the scientists who discovered the original SARS virus, in 2003, submitted the first paper to describe a protocol for testing for SARS-CoV-2.
  • That protocol would form the basis for a test disseminated, early on, by the World Health Organization
  • That same day, Messonnier announced that the C.D.C. had finalized its own test⁠, which it used to confirm the first known case of COVID-19 in the U.S.
  • The U.W. virology lab
  • started, probably in earnest in mid-January, to prepare what we call a laboratory-developed test,⁠
  • It took a team at the lab, working under the direction of Alex Greninger, about two weeks to develop a working version
  • But, as soon as Alex Azar, the Secretary of Health and Human Services, declared a public-health emergency, on February 4th, a new regulatory regime took effect. From that point on, any lab that wanted to conduct its own tests for the new coronavirus would first need to secure something called an Emergency Use Authorization from the F.D.A.
  • This shift in the regulations sounds perverse, since it restricts the use of new tests at precisely the moment they’re most needed.
  • E.U.A. process is supremely flexible.
  • triumph of modern medical science
  • hen there’s a big emergency and we feel like we should really do something, it gets hard. It’s a little frustrating. We’ve got a lot of scientists and doctors and laboratory personnel who are incredibly good at making assays. What we’re not so good at is figuring out all the forms and working with the bureaucracy of the federal government.”
  • At one point, he was very frustrated because he’d e-mailed them what we were doing so they could review it,”
  • Here we are in this SARS-CoV-2 crisis, and you have to send them something through the United States Postal Service. It’s just shocking.
  • Despite these difficulties, Jerome said, the F.D.A. ultimately proved responsive to the lab’s entreaties. “They had good and substantive feedback that made our testing better, and the response time was typically just a couple of days.”
  • believe it was, February 29th,” he said. “And then we got a specimen from one of the people who were the two original cases in Washington
  • The E.U.A. regulations, however, prohibited the lab from reporting the results to the doctors who had ordered the tests for their patients.
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    "Sharfstein, too, thinks that it's fair to criticize the federal government for not recognizing that its pandemic plans had a single point of failure. The C.D.C. quickly developed a working test, and it was understandable, at some level, that people at the Centers thought that fixing the faulty reagents for the public-health labs would be faster than shifting to an entirely different protocol. Nevertheless, Sharfstein said, "Why are we relying only on the C.D.C.? What the F.D.A. could have done, and eventually did do, is say, 'You can use other approaches.' " Even so, he said, "I don't think it's quite fair to totally blame the F.D.A. for this. The F.D.A. can design an approach to support the public-health strategy, but someone has to tell F.D.A. the public-health goal." The delay in clearly establishing those goals, he said, shows why the decision to shut down the N.S.C. directorate was so consequential. "People talk about, like, why does it matter that they closed the White House office on pandemic preparedness? This is one reason.""
Dennis OConnor

The Lancet: Statement in support of the scientists, public health professionals, and me... - 1 views

  • Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19
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    March 7, 2020: The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins. We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin. Scientists from multiple countries have published and analysed genomes of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),1 and they overwhelmingly conclude that this coronavirus originated in wildlife,2, 3, 4, 5, 6, 7, 8, 9, 10 as have so many other emerging pathogens.11, 12 This is further supported by a letter from the presidents of the US National Academies of Science, Engineering, and Medicine13 and by the scientific communities they represent. Conspiracy theories do nothing but create fear, rumours, and prejudice that jeopardise our global collaboration in the fight against this virus. We support the call from the Director-General of WHO to promote scientific evidence and unity over misinformation and conjecture.14 We want you, the science and health professionals of China, to know that we stand with you in your fight against this virus.
Dennis OConnor

Initial COVID-19 infection rate may be 80 times greater than originally reported | Penn... - 0 views

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    "Now, a new study from Penn State estimates that the number of early COVID-19 cases in the U.S. may have been more than 80 times greater and doubled nearly twice as fast as originally believed."
Dennis OConnor

The proximal origin of SARS-CoV-2 | Nature Medicine - 1 views

  • Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data
  • Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.
  • The receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome1,2. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors and for determining the host range of SARS-CoV-like viruses7.
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  • Theories of SARS-CoV-2 originsIt is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus.
  • the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone
  • we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer.
  • COVID-19 were linked to the Huanan market in Wuhan
  • it is likely that bats serve as reservoir hosts for its progenitor
  • Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-221
  • Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled
  • For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog
  • It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission.
  • All SARS-CoV-2 genomes sequenced so
  • are thus derived from a common ancestor that had them too
  • Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 201923,
  • compatible with the earliest retrospectively confirmed cases
  • Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.
  • The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation1
  • it is reasonable to wonder why the origins of the pandemic matter
  • Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events.
  • More scientific data could swing the balance of evidence to favor one hypothesis over another.
Dennis OConnor

QDX_Ver2 | Qanik DX - 0 views

shared by Dennis OConnor on 16 Oct 20 - No Cached
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  •  
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Dennis OConnor

What We Know So Far About SARS-CoV-2 - The Atlantic - 0 views

  • March 20, 2020
  • One of the few mercies during this crisis is that, by their nature, individual coronaviruses are easily destroyed.
  • These viruses don’t endure in the world. They need bodies.
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  • To be clear, SARS-CoV-2 is not the flu. It causes a disease with different symptoms, spreads and kills more readily,
  • his family, the coronaviruses, includes just six other members that infect humans
  • OC43, HKU1, NL63, and 229E—have been gently annoying humans for more than a century, causing a third of common colds
  • MERS and SARS (or “SARS-classic,” as some virologists have started calling it)—both cause far more severe disease.
  • hy was this seventh coronavirus the one to go pandemic?
  • The structure of the virus provides some clues about its success. In shape, it’s essentially a spiky ball. Those spikes recognize and stick to a protein called ACE2
  • This is the first step to an infection
  • he exact contours of SARS-CoV-2’s spikes allow it to stick far more strongly to ACE2 than SARS-classic did
  • But in SARS-CoV-2, the bridge that connects the two halves can be easily cut by an enzyme called furin, which is made by human cells and—crucially—is found across many tissues. “This is probably important for some of the really unusual things we see in this virus,” says Kristian Andersen of Scripps Research Translational Institute.
  • SARS-CoV-2 seems to infect both upper and lower airways,
  • his double whammy could also conceivably explain why the virus can spread between people before symptoms show up
  • All of this is plausible but totally hypothetical; the virus was only discovered in January, and most of its biology is still a mystery.
  • The closest wild relative of SARS-CoV-2 is found in bats, which suggests it originated in a bat, then jumped to humans either directly or through another species.
  • Another coronavirus found in wild pangolins also resembles SARS-CoV-2
  • Indeed, why some coronaviruses are deadly and some are not is unclear. “There’s really no understanding at all of why SARS or SARS-CoV-2 are so bad but OC43 just gives you a runny nose,” Frieman says.
  • Once in the body, it likely attacks the ACE2-bearing cells that line our airways.
  • The immune system fights back and attacks the virus; this is what causes inflammation and fever
  • in extreme cases, the immune system goes berserk
  • These damaging overreactions are called cytokine storms.
  • they’re probably behind the most severe cases of COVID-19.
  • During a cytokine storm, the immune system isn’t just going berserk but is also generally off its game, attacking at will without hitting the right targets.
  • But why do some people with COVID-19 get incredibly sick, while others escape with mild or nonexistent symptoms
  • Age is a factor.
  • other factors—a person’s genes, the vagaries of their immune system, the amount of virus they’re exposed to, the other microbes in their bodies
  • “it’s a mystery why some people have mild disease, even within the same age group,”
  • Coronaviruses, much like influenza, tend to be winter viruses.
  • In the heat and humidity of summer, both trends reverse, and respiratory viruses struggle to get a foothold.
  • irus is tearing through a world of immunologically naive people, and that vulnerability is likely to swamp any seasonal variations.
  • And one recent modeling study concluded that “SARS-CoV-2 can proliferate at any time of year.
  • Unless people can slow the spread of the virus by sticking to physical-distancing recommendations, the summer alone won’t save us.
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    Dr. Michael Kurisu D.O.: We've known about SARS-CoV-2 for only three months, but scientists can make some educated guesses about where it came from and why it's behaving in such an extreme way.
Dennis OConnor

Researchers Cast Doubt On Theory Of Coronavirus Lab Accident : Goats and Soda : NPR - 1 views

  • April 23, 2020
  • Virus researchers say there is virtually no chance that the new coronavirus was released as result of a laboratory accident in China or anywhere else.
  • after corresponding with 10 leading scientists who collect samples of viruses from animals in the wild, study virus genomes and understand how lab accidents can happen, NPR found that an accidental release would have required a remarkable series of coincidences and deviations from well-established experimental protocols.
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  • All of the evidence points to this not being a laboratory accident," says Jonna Mazet, a professor of epidemiology at the University of California, Davis and director of a global project to watch for emerging viruses called PREDICT.
  • all believe that the virus was transmitted between animals and humans in nature, as has happened in previous outbreaks — from Ebola to the Marburg virus — and with other known coronaviruses such as SARS and MERS.
  • Regardless, genetic analysis shows the virus began to spread sometime in the fall or winter of 2019, says Robert Garry, a microbiologist at Tulane University. Those same analyses refuted an earlier theory that the virus was genetically engineered in a laboratory.
  • the exact route from nature to people remains a mystery,
  • Rather than a laboratory misstep, researchers believe that this new coronavirus reached humans in the same way that other coronaviruses have: through "zoonotic spillover," or humans picking up pathogens from wildlife.
  • The CDC estimates that 6 out of 10 infectious diseases in people come from animals, including diseases caused by coronaviruses.
  • "As we change the landscape to suit our purposes, we come more and more into contact with viruses and other pathogens that we don't have much exposure to," says Dr. Brian Bird, associate director of the OneHealth Institute at UC Davis School of Veterinary Medicine and a former CDC scientist.
  • "Zoonotic transmission" or "zoonotic spillover" generally happens three ways: through excretion (feces that comes into contact with humans), slaughter (meat consumed by humans) and vector-borne (an animal biting a human). But even under these circumstances, the virus must then overcome barriers within the human body, defeating the immune system, to successfully replicate and transmit between humans themselves.
  • Despite the evidence, misinformation about the virus's origins continue to proliferate. For Daszak, who has worked on other outbreaks, the pattern is all too familiar: "Every time we get a new virus emerging, we have people that say, 'This could have come from a lab,' " he says.
  • "It's a real shame that the conspiracy theories can get to the level they've got with policymakers,"
  • The political heat has strained the very scientific collaborations meant to detect these viruses as they emerge, warns Jonna Mazet.
  • Daszak says the time for finger-pointing is over. "We have a bat virus in my neighborhood in New York killing people," he says. "Let's get real about this."
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    "April 23, 2020"
Dennis OConnor

The Prime Cellular Targets for the Novel Coronavirus - NIH Director's Blog - 0 views

  • Posted on May 5th, 2020 by Dr. Francis Collins
  • it has been remarkable and gratifying to watch researchers from around the world pull together and share their time, expertise, and hard-earned data in the urgent quest to control this devastating virus.
  • a recent study that characterized the specific human cells that SARS-CoV-2 likely singles out for infection [1
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  • This work was driven by the mostly shuttered labs of Alex K. Shalek, Massachusetts Institute of Technology, Ragon Institute of MGH, MIT, and Harvard, and Broad Institute of MIT and Harvard, Cambridge; and Jose Ordovas-Montanes at Boston Children’s Hospital. In the end, it brought together (if only remotely) dozens of their colleagues in the Human Cell Atlas Lung Biological Network and others across the U.S., Europe, and South Africa.
  • The discovery suggests that SARS-CoV-2 and potentially other coronaviruses that rely on ACE2 may take advantage of the immune system’s natural defenses.
  • t’s clear that these new findings, from data that weren’t originally generated with COVID-19 in mind, contained several potentially important new leads. This is another demonstration of the value of basic science.
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    "Posted on May 5th, 2020 by Dr. Francis Collins"
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