New Coronavirus News from 27 Jul 2022

New studies suggest Covid-19 likely originated from Wuhan wet market [CNN, 27 Jul 2022]

By Jen Christensen
(CNN)In June, the World Health Organization recommended that scientists continue to research all possible origins of the Covid-19 pandemic, including a lab leak. Two newly published studies take totally different approaches but arrive at the same conclusion: The Huanan Seafood Market in Wuhan, China, was most likely the epicenter for the coronavirus.
The studies were posted online as preprints in February but have now undergone peer review and were published Tuesday in the journal Science.

In one, scientists from around the world used mapping tools and social media reports to do a spatial and environmental analysis. They suggest that although the "exact circumstances remain obscure," the virus was probably present in live animals sold at the market in late 2019. The animals were held close together and could easily have exchanged germs. However, the study does not determine which animals may have been sick.

The researchers determined that the earliest Covid-19 cases were centered at the market among vendors who sold these live animals or people who shopped there. They believe that there were two separate viruses circulating in the animals that spilled over into people.

"All eight COVID-19 cases detected prior to 20 December were from the western side of the market, where mammal species were also sold," the study says. The proximity to five stalls that sold live or recently butchered animals was predictive of human cases.

"The clustering is very, very specific," study co-author Kristian Andersen, a professor in the Department of Immunology and Microbiology at Scripps Research, said Tuesday.

The "extraordinary" pattern that emerged from mapping these cases was very clear, said another co-author, Michael Worobey, department head of Ecology and Evolutionary Biology at the University of Arizona.

The researchers mapped the earliest cases that had no connection to the market, Worobey noted, and those people lived or worked in close proximity to the market.

"This is an indication that the virus started spreading in people who worked at the market but then started that spread ... into the surrounding local community as vendors went into local shops, infected people who worked in those shops," Worobey said.

The other study takes a molecular approach and seems to determine when the first coronavirus infections crossed from animals to humans.

The earliest version of the coronavirus, this research shows, probably came in different forms that the scientists call A and B. The lineages were the result of at least two cross-species transmission events into humans.

The researchers suggest that the first animal-to-human transmission probably happened around November 18, 2019, and it came from lineage B. They found the lineage B type only in people who had a direct connection to the Huanan market.

The authors believe that lineage A was introduced into humans from an animal within weeks or even days of the infection from lineage B. Lineage A was found in samples from humans who lived or stayed close to the market.

"These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported," the study says. "As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events."

The likelihood that such a virus would emerge from two different events is low, acknowledged co-author Joel Wertheim, an associate adjunct professor of medicine at the University of California, San Diego.

"Now, I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare, but once all the conditions are in place -- that is a zoonotic virus capable of both human infection and human transmission that is in close proximity to humans -- the barriers to spillover have been lowered such that multiple introductions, we believe, should actually be expected," Wertheim said.

Andersen said the studies don't definitively disprove the lab leak theory but are extremely persuasive, so much so that he changed his mind about the virus' origins.

"I was quite convinced of the lab leak myself, until we dove into this very carefully and looked at it much closer," Andersen said. "Based on data and analysis I've done over the last decade on many other viruses, I've convinced myself that actually the data points to this particular market."

Worobey said he too thought the lab leak was possible, but the epidemiological preponderance of cases linked to the market is "not a mirage."

"It's a real thing," he said. "It's just not plausible that this virus was introduced any other way than through the wildlife trade."

To reduce the chances of future pandemics, the researchers hope they can determine exactly what animal may have first become infected and how.

"The raw ingredients for a zoonotic virus with pandemic potential are still lurking in the wild," Wertheim said. He believes the world needs to do a much better job doing surveillance and monitoring animals and other potential threats to human health.

Andersen said that although we can't prevent outbreaks, collaboration between the world's scientists could be key to the difference between a disease with a small impact and one that kills millions.

"The big question we need to ask ourselves is -- the next time this happens, because it will happen -- how do we go from detecting that outbreak early and preventing that outbreak so it doesn't become a pandemic?"

Scientists hone argument that coronavirus came from Wuhan market [The Washington Post, 27 Jul 2022]

By Joel Achenbach

The coronavirus pandemic began in separate viral spillovers — at least two but perhaps as many as two dozen — from live animals sold and butchered in late 2019 at the Huanan Seafood Market in Wuhan, China, according to two papers published Tuesday in the journal Science.

The publication of the papers, which underwent five months of peer review and revisions by the authors, is unlikely to quell the rancorous debate about how the pandemic began and whether the virus emerged from a Chinese laboratory. And the authors acknowledge there are many unknowns requiring further investigation — most notably, which animals were involved.

“Everything upstream of this — which animals, where did they come from, how it’s all connected — is completely unknown at this stage,” Kristian Andersen, an immunologist at Scripps Research, said in a media briefing Tuesday.

“Have we disproven the lab leak theory? No, we have not. Will we ever be able to? No. But there are ‘possible’ scenarios and there are ‘plausible’ scenarios. … ‘Possible’ does not mean equally likely,” Andersen said.

A natural origin of the pandemic — a “zoonosis” — has long been a favored theory among scientists for the simple reason that most pandemics, including the SARS coronavirus outbreak of 2002-2003, have started that way. Andersen and his colleagues believe multiple lines of evidence, including the clustering of early cases of covid-19 around the market, make a market origin not only a likely scenario but the only one that fits the data.

The “lab leak” conjecture was initially dismissed in most mainstream media as a conspiracy theory. There are numerous lab leak scenarios, and many have focused on the Wuhan Institute of Virology, a major research center that studies coronaviruses.

Scientists there say they never had the virus in their laboratory. But outside experts questioned whether the laboratory adhered sufficiently to safety measures when researching viruses. Chinese authorities limited access to the laboratories by outside investigators.
Amateur sleuths created online communities that steadily raised suspicions about a possible lab leak. Pressure to investigate the hypothesis came amid the struggles of the scientific community to nail down how the virus entered the human population.

In May 2021, the journal Science published a letter from 18 scientists calling for an investigation into the virus’s origin that would include exploration of the lab leak theory. Soon after that, President Biden asked his intelligence agencies to investigate all possible origins of the pandemic. The review concluded that the virus was not an engineered bioweapon, but otherwise failed to reach a conclusion about where it came from.

Among the scientists who signed the letter to Science was Michael Worobey, an evolutionary virologist at the University of Arizona who felt the lab leak thesis deserved attention even if it wasn’t the most likely origin. But Worobey soon became convinced that the virus came out of the market. Worobey is the lead author of the new paper that contends the market was the pandemic’s epicenter.

The researchers scoured data about the earliest patients, many of whom had direct links to the market or lived nearby. The geography of early community spread showed infections radiating outward from the vicinity of the market, Worobey said: “It’s an insane bull’s eye.”

Moreover, when the market was first identified as the site of a cluster of cases, Chinese investigators took environmental samples searching for traces of the virus. A disproportionate number of positive virus traces came from the section of the market where live animals had been sold, the new study reports.

“The virus started spreading in people who worked at the market, but then started spreading in the surrounding local community as vendors went to local shops, and infected people who worked in those shops,” Worobey suggested.

Worobey is not new to this issue. Last year, he wrote a “Perspective” article in Science that said the geographical clustering of cases in and around the market could not be explained away as “ascertainment bias,” meaning the clustering was not simply the result of investigators knocking on doors in that area after the market outbreak was detected.

He believes any alternative scenario — such as a lab leak — is implausible.

“It now puts us at a point where we know that the Huanan market was the epicenter of this pandemic. That much is now established. If others want to argue with that, they’re now essentially taking a pseudoscientific approach,” Worobey said in an interview Tuesday. “Even though you don’t have the smoking gun of, ‘Yes we’ve sampled the raccoon dog with the virus in December,’ when you put it all together, it’s the only theory that actually explains all the data.”

Angela Rasmussen, a virologist at the University of Saskatchewan and co-author of one of the new papers, said in an email that she agreed with Worobey: “There is no alternative explanation that fits the facts, so anyone trying to come up with one will have to become adept at willful ignorance, a logical contortionist, or simply a fabulist.”

The contention by the authors of a natural origin of the pandemic is not new: The same two papers in an earlier form were posted online in February on a “preprint” site. But at that point, they existed in peer-review limbo — something that could be reported in a news story but lacking the stature of studies that have survived scrutiny by knowledgeable outsiders and journal editors.

The second paper published Tuesday in Science reports that genetic evidence and computer modeling suggest the virus spilled into the human population not just once, but on multiple occasions in late 2019. Genomic analysis of early cases shows two distinct lineages, called A and B, that had to have come from separate spillovers. Both lineages were found in environmental samples taken in the market, according to a preprint paper from Chinese researchers in February.

Promoters of the lab leak theory counter that the market was more likely a superspreader site. The virus could have been brought there by someone infected at a laboratory, or someone exposed to an infected lab worker, for example.

The argument for a market origin also relies on Chinese data that may be unreliable, Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Institute, said in an interview earlier this year. He said he feels the data are “inconclusive.”

“I feel the data released by the Chinese government should be treated with a healthy grain of salt,” Bloom said.

There is no proof that the virus or its immediate ancestor was in any laboratory before the outbreak in Wuhan. But the ongoing mystery of the pandemic’s origin has called attention to the kind of research on viruses — including “gain of function” experiments — that some critics say is too risky. The U.S. National Institutes of Health, immersed in the controversy because it helped fund some research at the Wuhan Institute of Virology, this year said it was reviewing its policies for ensuring laboratory safety and security.

Sen. Rand Paul (R-Ky.), who favors a laboratory origin explanation, said at an April 30 rally in Kentucky that if Republicans take power in the Senate after the midterm elections, he will use subpoena power to “get to the bottom of where this virus came from.”

Chinese scientists have denied that the virus was present in their lab. The virus, according to Andersen and other virologists who have studied it, does not appear to be manipulated or engineered, and its genetic features could have been produced through evolution.

Still, the controversy about coronavirus research is not likely to fade.

Jeffrey Sachs, a Columbia University economist, heads a commission sponsored by the Lancet journal expected to produce a report this fall on the pandemic, including the origin of the virus.
He recently co-authored an article in the Proceedings of the National Academy of Sciences calling for a probe of the pandemic origin through a “bipartisan congressional inquiry with full investigative powers.”

On Tuesday, after Science published the two papers, Sachs said in an email that he still favors the lab leak theory: “The two competing hypotheses, natural spillover and laboratory creation, are both viable. They should be compared directly against each other. In my view, the laboratory creation hypothesis is the more straightforward and more credible.”

The new papers do not declare “case closed” but are useful, noted David Relman, a professor of medicine and microbiology at Stanford University who was among the signers of the 2021 letter to Science calling for a probe of all possible pandemic origins. He said he would like to see a similarly thorough forensic study of the lab leak hypothesis.

“I don’t think we can say that we now know that it started here. I think we can say that something interesting happened in this part of the city,” Relman said. “We don’t have any [coronavirus] positive animals at the market.”

Andersen, the Scripps Research scientist, has been entangled in the virus origin controversy for more than two years. He was lead author of an early paper, published in Nature Medicine, saying the virus was clearly not engineered. But his first impression of the virus had been that it looked unnatural, and only after doing more research did he conclude that its features could have been produced through evolution.

On Tuesday, Andersen reiterated that he initially thought the novel coronavirus probably came from a laboratory. But all signs now point to the market, he said.

“It’s not a formal proof, again, but it is so strong in my opinion that any other version, a lab leak for example, would have to be able to explain all this evidence,” he said. “It’s just not plausible.”

New Coronavirus News from 26 Jul 2022

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 [Science, 26 Jul 2022]

Authored by JONATHAN E. PEKAR, ANDREW MAGEE, EDYTH PARKER NIEMA MOSHIRI, KATHERINE IZHIKEVICHJENNIFER L. HAVENS, KARTHIK GANGAVARAPU, LORENA MARIANA MALPICA SERRANO, ALEXANDER CRITS-CHRISTOPHNATHANIEL, L. MATTESONMARK ZELLERJOSHUA, I. LEVY, JADE C. WANG, SCOTT HUGHESJUNGMIN LEE, HEEDO PARK, MAN-SEONG PARK , KATHERINE ZI YAN CHING, RAYMOND TZER PIN LIN, MOHD NOOR MAT ISA, YUSUF MUHAMMAD NOOR, TETYANA I. VASYLYEVA, ROBERT F. GARRY, EDWARD C. HOLMES, ANDREW RAMBAUT, MARC A. SUCHARD, KRISTIAN, G. ANDERSEN, MICHAEL WOROBEY AND JOEL O. WERTHEIM

Abstract
Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.