Newly released documents indicate that a U.S. genetic database had received the sequence of the coronavirus two weeks before it was made public by others.In late December 2019, eight pages of genetic code were sent to computers at the National Institutes of Health in Bethesda, Md.Unbeknown to American officials at the time, the genetic map that had landed on their doorstep contained critical clues about the virus that would soon touch off a pandemic.The genetic code, submitted by Chinese scientists to a vast public repository of sequencing data run by the U.S. government, described a mysterious new virus that had infected a 65-year-old man weeks earlier in Wuhan. At the time the code was sent, Chinese officials had not yet warned of the unexplained pneumonia sickening patients in the central city of Wuhan.But the U.S. repository, which was designed to help scientists share run-of-the-mill research data, never added the submission it received on Dec. 28, 2019, to its database. Instead, it asked the Chinese scientists three days later to resubmit the code with certain additional technical details. That request went unanswered.It took almost another two weeks for a separate pair of virologists, one Australian and the other Chinese, to work together to post the genetic code of the new coronavirus online, setting off a frantic global effort to save lives by building tests and vaccines.The initial attempt by Chinese scientists to publicize the crucial code was revealed for the first time in documents released on Wednesday by House Republicans investigating Covid’s origins. The documents reinforced questions circulating since early 2020 about when China learned of the virus that was causing its unexplained outbreak — and also drew attention to gaps in the American system of monitoring for dangerous new pathogens.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

A new study describes a method for faster and more precise diagnoses, which can help surgeons decide how aggressively to operate.Once their scalpels reach the edge of a brain tumor, surgeons are faced with an agonizing decision: cut away some healthy brain tissue to ensure the entire tumor is removed, or give the healthy tissue a wide berth and risk leaving some of the menacing cells behind.Now scientists in the Netherlands report using artificial intelligence to arm surgeons with knowledge about the tumor that may help them make that choice.The method, described in a study published on Wednesday in the journal Nature, involves a computer scanning segments of a tumor’s DNA and alighting on certain chemical modifications that can yield a detailed diagnosis of the type and even subtype of the brain tumor.That diagnosis, generated during the early stages of an hourslong surgery, can help surgeons decide how aggressively to operate, the researchers said. In the future, the method may also help steer doctors toward treatments tailored for a specific subtype of tumor.“It’s imperative that the tumor subtype is known at the time of surgery,” said Jeroen de Ridder, an associate professor in the Center for Molecular Medicine at UMC Utrecht, a Dutch hospital, who helped lead the study. “What we have now uniquely enabled is to allow this very fine-grained, robust, detailed diagnosis to be performed already during the surgery.”Their deep learning system, called Sturgeon, was first tested on frozen tumor samples from previous brain cancer operations. It accurately diagnosed 45 of 50 cases within 40 minutes of starting genetic sequencing. In the other five cases, it refrained from offering a diagnosis because the information was unclear.The system was then tested during 25 live brain surgeries, most of them on children, alongside the standard method of examining tumor samples under a microscope. The new approach delivered 18 correct diagnoses and failed to reach the needed confidence threshold in the other seven cases. It turned around its diagnoses in less than 90 minutes, the study reported — short enough for it to inform decisions during an operation.Currently, in addition to examining brain tumor samples under a microscope, doctors can send them for more thorough genetic sequencing.But not every hospital has access to that technology. And even for those that do, it can take several weeks to receive results, said Dr. Alan Cohen, the director of the Johns Hopkins Division of Pediatric Neurosurgery and a cancer specialist.“We have to start treatment without knowing what we’re treating,” Dr. Cohen said.The new method uses a faster genetic sequencing technique and applies it only to a small slice of the cellular genome, allowing it to return results before a surgeon has started operating on the edges of a tumor.Dr. de Ridder said that the model was powerful enough to deliver a diagnosis with sparse genetic data, akin to someone recognizing an image based on only one percent of its pixels, and from an unknown portion of the image.“It can figure out itself what it’s looking at and make a robust classification,” said Dr. de Ridder, who is also a principal investigator at Oncode Institute, a cancer research center in the Netherlands.But some tumors are still difficult to diagnose. The samples taken during surgery are about the size of a kernel of corn, and if they include some healthy brain tissue, the deep learning system may struggle to pick out enough tumor-specific markers.In the study, doctors dealt with that by asking the pathologists examining samples under a microscope to flag the ones with the most tumor for sequencing, said Marc Pagès-Gallego, a bioinformatician at UMC Utrecht and a co-author of the study.There can also be differences within a single patient’s tumor cells, meaning that the small segment being sequenced may not be representative of the entire tumor. Some less common tumors may not correspond to those that have previously been classified. And some tumor types are easier to classify than others.Other medical centers have already started applying the new method to surgical samples, the study’s authors said, suggesting that it can work in other people’s hands.But Dr. Sebastian Brandner, a professor of neuropathology at University College London, said that sequencing and classifying tumor cells often still required significant expertise in bioinformatics as well as workers who are able to run, troubleshoot and repair the technology.“Implementation itself is less straightforward than often suggested,” he said.Brain tumors are also the most well-suited to being classified by the chemical modifications that the new method analyzes; not all cancers can be diagnosed that way.The new method is part of a broad movement toward bringing molecular precision to diagnosing tumors, potentially allowing scientists to develop targeted treatments that are less damaging to the nervous system. But translating a deeper knowledge of tumors to new therapies has proved difficult.“We’ve made some gains,” Dr. Cohen said, “but not as many in the treatment as in the understanding of the molecular profile of the tumors.”

Two episodes, where the Republican senator froze and did not respond to some questions, may be symptoms of a serious illness, according to neurologists not involved in his medical care.A four-line letter, signed by the attending physician of Congress and released by Senator Mitch McConnell on Thursday, suggested that his recent spells of speechlessness were linked to “occasional lightheadedness” perhaps brought on by his recovery from a concussion last winter or “dehydration.”But seven neurologists, relying on what they described as unusually revealing video of Mr. McConnell freezing up in public twice recently, said in interviews Thursday and Friday that the episodes captured in real time likely pointed to more serious medical problems afflicting the longtime Republican leader.Some of the neurologists, while cautioning that they could not diagnose the minority leader from afar, said that the letter and other comments from Mr. McConnell’s office appeared to fall short of explaining why he abruptly stopped speaking during news conferences in late July and again on Wednesday.“If I gave that tape to a medical student and that was his explanation, I’d fail him,” said Dr. Orrin Devinsky, a professor of neurology at the NYU Grossman School of Medicine, referring to the account given by the attending physician of Congress on Thursday. “Medically, these episodes need to be taken seriously.”The neurologists said that the episodes justified close medical attention and could prompt treatment to keep them from recurring. While several possibilities were suggested, including mini-strokes, doctors said that the spells appeared most consistent with focal seizures, which are electrical surges in one region of the brain.The senator’s aides have not revealed what type of follow-up care Mr. McConnell may be receiving, and his office said on Friday it had nothing to add beyond the letter by the Congressional physician, Dr. Brian P. Monahan.More details about the medical history of Mr. McConnell, 81, including whether he has been having such episodes off camera, would also help rule out other possible explanations for the spells, neurologists said.Whether caused by seizures or mini-strokes or something else, spells like Mr. McConnell’s would not preclude most patients from working or socializing normally, doctors said.“Seizures have a stigma in our society, and that’s unfortunate because these are very brief electrical interruptions in behavior,” said Dr. Jeffrey Saver, a professor of neurology at U.C.L.A. “Between those rare episodes, which are usually well controlled with medicines, people function perfectly normally.”Still, experts said that seizures carried some elevated risk of cognitive or behavioral problems and could affect older patients differently.Rarely does the public get as complete a glimpse of a serious medical event in a public figure as it did twice in recent weeks with Mr. McConnell. For neurologists, videos like those showing Mr. McConnell from the moment he appeared to lose the ability to speak are far more than mere curiosities.They can help form the basis of a diagnosis, as homemade videos of everyday patients occasionally do in standard neurology practices.“They’re very helpful, because you’re not subject to the vagaries of someone’s description and you can capture the beginning of it, which is important especially for seizures,” said Dr. Anthony Kim, a professor of neurology at the University of California, San Francisco.Details as small as the direction in which people’s eyes are pointed during such an episode offer potential clues about the cause, Dr. Kim said.After watching Mr. McConnell’s symptoms play out — his abrupt stop in speech, his eyes fixed in the distance, his seeming recovery after about 30 seconds — Dr. Kim said that “the possibility at the top of my list would be a seizure.”That Mr. McConnell’s second spell so closely mirrored the first pointed even more strongly to a seizure, neurologists said.Mini-strokes, which result from a clot that reduces blood flow to the brain, can also cause brief periods of impaired speech. But they rarely produce the same constellation of symptoms each time they recur, given that clots are unlikely to travel at random to the same part of the brain twice.Focal seizures, on the other hand, are often triggered by an irregularity in one specific part of the brain, creating what doctors refer to as stereotypic symptoms. They are known to stop patients dead in their tracks, seeming to cut them off from their surroundings.Patients can often respond reflexively to questions during such an episode — as Mr. McConnell did on Wednesday, saying “yeah” when asked if he had heard a reporter’s question — even if they appear unable to voice their thoughts or engage with their environment.Mr. McConnell suffered a concussion in March, a risk factor for seizures. The seizures can be caused by a bleed in the brain or a scar from a traumatic head injury. Previous strokes or other kinds of damage to brain tissue can also lead to seizures in older people, who as a group experience the onset of seizures almost as often as children do.Some seizures are provoked by triggers like abnormal blood sugar levels. But if someone has had two seizures that cannot be explained in that way, neurologists said that would typically be enough for a diagnosis of epilepsy, a common neurological disorder affecting more than three million Americans that can arise at any age. They would generally prescribe anti-seizure medication.“Two seizures you definitely would want to treat,” said Dr. Sami Khella, the chief of neurology at Penn Presbyterian Medical Center. “You don’t want them to happen — they’re not good for you.”Many patients function completely normally and show normal brain wave activity between seizures, allowing them to remain active and working even as they are forced to forgo activities like driving.But they do cause patients to miss periods of time during episodes. A seizure at an inopportune moment, like when crossing the street, can be dangerous. And focal seizures involving one region of the brain can generalize, causing episodes characterized by jerking movements or epileptic spasms.Beyond that, one or two seizures can beget more, a cycle that neurologists try to interrupt with treatment. “The more the brain seizes, the more it learns to seize,” Dr. Khella said.Other complications can follow. A phenomenon known as sudden, unexpected death in epilepsy kills an estimated one in 1,000 people with epilepsy each year.“If you do get epilepsy as an elderly individual, there are concerns about things like memory, about cognitive function, because your resilience at 80 is going to be far less than when you’re 20 or 30,” said Dr. Devinsky, who directs NYU Langone’s Comprehensive Epilepsy Center.Neurologists said they could not rule out other possible explanations for Mr. McConnell’s episodes.Dr. Gavin Britz, a neurosurgeon at Houston Methodist, said he would want to exclude Parkinson’s disease, which can also cause freezing episodes.But neurologists agreed that suggestions that Mr. McConnell was merely lightheaded, while possible, were difficult to square with the video. Dehydration could exacerbate other conditions, they said, but such patients would be unlikely to stay upright or recover so quickly without fluids, as Mr. McConnell appeared to do.“We don’t have 100 percent information, so we’re kind of in the dark,” Dr. Devinsky said. “But we do have this very powerful clinical information, which is quite honestly how I have to diagnose seizures and epilepsy all the time, often without the video.”

The drug Wegovy eased issues for people with a type of heart problem, adding to the treatment’s benefits beyond weight loss.One of the leading new obesity drugs, Wegovy, eased symptoms and raised the quality of life of patients with obesity and a common type of heart failure, a study funded by the drug’s maker found, adding to the evidence that the medications can produce health benefits beyond weight loss.The study, published on Friday in The New England Journal of Medicine, evaluated the drug in people with a condition known as preserved ejection fraction in which the heart pumps normally but has lost the flexibility needed to fill with blood. The condition accounts for roughly half of all heart failure cases.Patients given Wegovy in the trial showed greater improvements in physical fitness and in symptoms like fatigue and shortness of breath than those administered a placebo. The study, which included 529 participants and lasted for a year, was not designed to assess cardiac emergencies, but it found that 12 patients on the placebo and only one on Wegovy were hospitalized or required an urgent medical visit for heart failure.The drug showed more pronounced relief of heart failure symptoms than other treatments, the study said.“This is a huge patient population that is extremely symptomatic, for which we’ve had very few if any treatment options, and in which obesity is highly prevalent,” said Dr. Mikhail Kosiborod, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City and the study’s lead investigator, who also consults for Novo Nordisk, the maker of Wegovy. “It’s going to be a true paradigm shift.”Cardiologists used to see obesity as a condition that simply coexisted with heart failure. But the new study strengthened the evidence of obesity being a main driver of the disease.“It’s a proof of concept that in many patients with this type of heart failure, where obesity is in fact causal, it needs to be treated as a root cause of heart failure and needs to be targeted as a therapeutic strategy,” Dr. Kosiborod said.Another study evaluating the drug in heart failure patients with obesity and diabetes is expected to wrap up this year. If that study, too, produces promising results, Novo Nordisk has said it could seek to have the drug formally recommended for the treatment of heart failure.Scientists who did not work on the trial said it would be important to study the drug over longer periods in more patients, allowing researchers to determine whether it actually reduced the likelihood of hospitalizations or deaths. But given the severity of physical limitations and symptoms in patients with this type of heart failure, the improvements on those measures alone were notable, they said.On a 100-point measure of quality of life and physical abilities, patients given Wegovy experienced a greater improvement of their symptoms by roughly eight more points than patients on the placebo, according to the study. People on Wegovy also showed greater gains on a six-minute walk test.“It’s a short trial, and so we can’t say much about long-term sustained benefits, but I think the magnitude of the benefit is impressive relative to what other interventions have shown in the same population,” said Dr. Daniel Drucker, a senior scientist at the Lunenfeld Tanenbaum Research Institute at Mt. Sinai Hospital in Toronto who has studied the new drugs. He has received fees from Novo Nordisk but was not involved in the latest trial.Wegovy and another version of the same drug for diabetes patients, Ozempic, have quickly become popular for the significant weight loss results they have shown — so much so that Novo Nordisk has struggled to meet growing demand.But the latest study built on other recent evidence that the drug does more than cut weight.The company, for example, announced this month that Wegovy also slashed the risk of heart complications by 20 percent among a different pool of patients in a large trial, a result that was seen as crucial for persuading more insurers to cover the new weight loss drugs. Researchers are waiting for the company to release the underlying data to the study to examine the topline results.“Obesity is associated with 200 other obesity-related diseases,” said Dr. Ania Jastreboff, an endocrinologist and obesity medicine specialist at Yale University who consults for makers of obesity drugs. “If we treat this one disease, we can potentially impact the health of so many patients in many different ways, and this is yet another important example.”Experts believe that weight loss on its own probably accounted for some of the improvements in patients’ heart health. But determining exactly how big a role weight loss played and what other factors may have contributed will require more research.The heart failure study released on Friday, for example, found indications that Wegovy may have reduced inflammation. Patients on the drug also had lower levels of an important marker of heart congestion, another sign that the drug is doing something that may have an effect on heart failure.“We still need to understand that better,” Dr. Kosiborod said.

Senator Dianne Feinstein developed this rare and potentially debilitating complication after a shingles infection.Dianne Feinstein, a Democratic senator from California, has returned to the Capitol after spending more than two months recovering from shingles. The disease, often characterized by a painful rash, is triggered by the same virus that causes chickenpox, which stays in people’s bodies for life and, years later, can become reactivated.For Ms. Feinstein, 89, the virus also brought on a previously unreported case of encephalitis, a rare but potentially debilitating complication in which the brain swells. The condition is often caused by an infection or an immune response.What are the symptoms of encephalitis?Post-shingles encephalitis can cause headache, fever, sensitivity to light, vomiting, confusion, a stiff neck or even seizures.It can also leave some patients with more lasting problems. Those include memory or language trouble, sleep disorders, mood disorders, walking difficulty and other cognitive problems. Older patients tend to have the most trouble recovering.There are milder and more serious cases. A French study from last year looking at several dozen critically ill patients with the condition found that about one-fifth of them were significantly disabled a year after being hospitalized and one-third had died.A separate study in Denmark from 2020 found that roughly half of post-shingles encephalitis patients admitted to hospitals were at least moderately disabled three months after being discharged.How common is the condition?Dr. Adrien Mirouse, a physician and immunologist based at Sorbonne University in Paris, who led the French study last year, estimated that fewer than 1 percent of shingles patients go on to develop encephalitis.But precise rates, he said, were difficult to pin down: Milder cases often go unreported, making it hard to know the real number of patients with shingles or post-shingles encephalitis.Brain swelling has historically been thought to affect mostly those shingles patients with immune deficiencies. But recent studies have found that many patients are simply older and struggling with a routine weakening of their immune systems. For that reason, the condition may be increasingly common as populations age, experts said.What is the outlook for patients?It is not entirely clear why some shingles patients who develop encephalitis fare better or worse with the condition. Older age appears to put people at greater risk for more serious problems.But published case studies have described even younger patients who show signs of retrieving their cognitive functions, only to deteriorate again.“You may have some symptoms that last after the encephalitis,” Dr. Mirouse said of patients. “It’s not sure you will be able to recover completely. That’s true at 89, it’s also true at 30 or 20.”Ms. Feinstein may have been at higher risk for developing encephalitis because her shingles had spread to her face and neck, which is known to put patients at risk of brain inflammation.How else can shingles affect people’s cognition?Inflammation alone can damage cells in the brain.But shingles can also contribute to cognitive decline in other ways, including by damaging blood vessels of the brain, said Dr. Sharon E. Curhan, a physician and epidemiologist at Brigham and Women’s Hospital and Harvard Medical School, who is studying the link between shingles and changes in cognition.Shingles patients also face a significantly higher long-term risk of having a stroke, a condition that itself can lead to cognitive decline, according to a study led by Dr. Curhan published last year.Ms. Feinstein had received a shingles vaccine, which in most people provides strong protection against the virus and the complications that can follow. Federal health officials recommend the vaccine for people 50 and older and younger adults with weakened immune systems.

Using mRNA tailored to each patient’s tumor, the vaccine may have staved off the return of one of the deadliest forms of cancer in half of those who received it.Five years ago, a small group of cancer scientists meeting at a restaurant in a deconsecrated church hospital in Mainz, Germany, drew up an audacious plan: They would test their novel cancer vaccine against one of the most virulent forms of the disease, a cancer notorious for roaring back even in patients whose tumors had been removed.The vaccine might not stop those relapses, some of the scientists figured. But patients were desperate. And the speed with which the disease, pancreatic cancer, often recurred could work to the scientists’ advantage: For better or worse, they would find out soon whether the vaccine helped.On Wednesday, the scientists reported results that defied the long odds. The vaccine provoked an immune response in half of the patients treated, and those people showed no relapse of their cancer during the course of the study, a finding that outside experts described as extremely promising.The study, published in Nature, was a landmark in the yearslong movement to make cancer vaccines tailored to the tumors of individual patients.Researchers at Memorial Sloan Kettering Cancer Center in New York, led by Dr. Vinod Balachandran, extracted patients’ tumors and shipped samples of them to Germany. There, scientists at BioNTech, the company that made a highly successful Covid vaccine with Pfizer, analyzed the genetic makeup of certain proteins on the surface of the cancer cells.Using that genetic data, BioNTech scientists then produced personalized vaccines designed to teach each patient’s immune system to attack the tumors. Like BioNTech’s Covid shots, the cancer vaccines relied on messenger RNA. In this case, the vaccines instructed patients’ cells to make some of the same proteins found on their excised tumors, potentially provoking an immune response that would come in handy against actual cancer cells.“This is the first demonstrable success — and I will call it a success, despite the preliminary nature of the study — of an mRNA vaccine in pancreatic cancer,” said Dr. Anirban Maitra, a specialist in the disease at the University of Texas MD Anderson Cancer Center, who was not involved in the study. “By that standard, it’s a milestone.”The study was small: Only 16 patients, all of them white, were given the vaccine, part of a treatment regimen that also included chemotherapy and a drug intended to keep tumors from evading people’s immune responses. And the study could not entirely rule out factors other than the vaccine having contributed to better outcomes in some patients.“It’s relatively early days,” said Dr. Patrick Ott of the Dana-Farber Cancer Institute.Beyond that, “cost is a major barrier for these types of vaccines to be more broadly utilized,” said Dr. Neeha Zaidi, a pancreatic cancer specialist at the Johns Hopkins University School of Medicine. That could potentially create disparities in access.But the simple fact that scientists could create, quality-check and deliver personalized cancer vaccines so quickly — patients began receiving the vaccines intravenously roughly nine weeks after having their tumors removed — was a promising sign, experts said.Since the beginning of the study, in December 2019, BioNTech has shortened the process to under six weeks, said Dr. Ugur Sahin, a co-founder of the company, who worked on the study. Eventually, the company intends to be able to make cancer vaccines in four weeks.And since it first began testing the vaccines about a decade ago, BioNTech has lowered the cost from roughly $350,000 per dose to less than $100,000 by automating parts of production, Dr. Sahin said.A personalized mRNA cancer vaccine developed by Moderna and Merck reduced the risk of relapse in patients who had surgery for melanoma, a type of skin cancer, the companies announced last month. But the latest study set the bar higher by targeting pancreatic cancer, which is thought to have fewer of the genetic changes that would make it ripe for vaccine treatments.In patients who did not appear to respond to the vaccine, the cancer tended to return around 13 months after surgery. Patients who did respond, though, showed no signs of relapse during the roughly 18 months they were tracked.Intriguingly, one patient showed evidence of a vaccine-activated immune response in the liver after an unusual growth developed there. The growth later disappeared in imaging tests.“It’s anecdotal, but it’s nice confirmatory data that the vaccine can get into these other tumor regions,” said Dr. Nina Bhardwaj, who studies cancer vaccines at the Icahn School of Medicine at Mount Sinai.Scientists have struggled for decades to create cancer vaccines, in part because they trained the immune system on proteins found on tumors and normal cells alike.Tailoring vaccines to mutated proteins found only on cancer cells, though, potentially helped provoke stronger immune responses and opened new avenues for treating any cancer patient, said Ira Mellman, vice president of cancer immunology at Genentech, which developed the pancreatic cancer vaccine with BioNTech.“Just establishing the proof of concept that vaccines in cancer can actually do something after, I don’t know, thirty years of failure is probably not a bad thing,” Dr. Mellman said. “We’ll start with that.”

After analyzing genetic data swabbed from a Wuhan market in early 2020, a virologist said it was unclear if animals for sale there had been infected.A new study of genetic data from a market in Wuhan, China, said the data did not support the case that the pandemic had started with illegally traded animals, touching off fresh debate about samples that other scientists see as critical pieces of the puzzle of how the coronavirus reached humans.The new study, which examined the relative amounts of animal and viral material in swabs taken from surfaces at the market in early 2020, said it was difficult to draw conclusions about whether given samples of the virus had come from infected live animals or were simply from incidental contamination.But several outside experts said the analysis, posted online this week by the study’s author, Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center, could have been affected by a number of unknown variables and decisions about how to filter the data.For those reasons, they said, the findings did not do much to sway their impression of previous studies. Samples from the market containing animal and viral genetic material, they said, were consistent with the possibility that an animal there — perhaps a raccoon dog — had spread the virus to people, but did not prove that had happened.“I think there’s a pretty reasonable chance they picked up an infected raccoon dog, but that doesn’t prove that was the origin,” said Frederic Bushman, a microbiologist at the University of Pennsylvania who specializes in analyzing samples like those taken from the Wuhan market, but who was not involved in any of the market studies. “I don’t think the Bloom paper changes my thinking that much.”Chinese researchers wrote about the market data last year and then made the genetic sequences available this year, allowing a team of international scientists to study them. That team wrote in a report last month that based on the data, they could not conclusively identify an animal that had passed the virus to people.But they said the data confirmed that animals believed to be susceptible to the virus, like raccoon dogs and masked palm civets, a small Asian mammal implicated in the SARS outbreak two decades ago, were being sold at the market in late 2019. Many of the earliest Covid-19 patients also worked or shopped at the market.Because the market was one of only four places in Wuhan reported to be selling live animals of the sort that could plausibly spread the virus, the scientists said it was unlikely that so many early patients were linked to the market purely by chance. They said the genetic data also built on other evidence, including that two early lineages of the virus had been at the market.This week’s study took a different approach to analyzing the gene sequences.Dr. Bloom investigated whether the amount of genetic material from the virus correlated with the amount of genetic material from susceptible animal species in the samples. If one species at the market was overwhelmingly responsible for shedding the virus, he said in an interview, he would have expected to see a clear link between the amount of genetic material from the virus and the amount from that species.But the study found no clear correlations of that kind. Instead, the strongest correlations involved various fish sold at the market that could not have been infected, an indication that infected people had probably deposited viral material where the fish was.Dr. Bloom said that finding suggested that the virus, also known as SARS-CoV-2, was spread widely across the market by the time the swabs were collected in early 2020.“In the same way we shouldn’t read much of anything into the fact that there’s a bunch of SARS-CoV-2 mixed with largemouth bass and catfish samples, we also shouldn’t read much into the fact that there’s a raccoon dog sample with a SARS-CoV-2 read,” Dr. Bloom said.A common raccoon dog.Buschkind/AlamyBut outside experts said that various features of the samples could throw off efforts to correlate animal and viral material. The international scientists said in their report that they had considered running a similar analysis, but that it risked producing misleading results. Dr. Bloom acknowledged that “it’s an open question of whether that is an informative thing to calculate at all.”Genetic material from the virus degrades quickly, said Christopher Mason, a specialist in environmental sampling at Weill Cornell Medicine. Crucially, viral material may decay at a different rate than material from animals, making it difficult to compare them in samples collected over the course of weeks after the market’s closure.It could be that fish were most closely associated with the virus simply because the fish were likely to have been frozen or refrigerated, slowing the decay of viral material in those samples, said Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium.The latest analysis “confirms that looking at these sorts of correlations tells you next to nothing with respect to which host species could have been a plausible source of the pandemic,” Dr. Wenseleers said. This leaves scientists in the same situation as before, he said, with market data that doesn’t offer conclusive evidence of any particular origin scenario.The new study also looked closely at a swab from a cart at the market in which the international team had found a trace of the virus alongside genetic signatures of raccoon dogs, but no detectable genetic material from humans.Dr. Bloom wrote that the swab had only a minuscule amount of viral material, and that it was not clear why Chinese researchers had classified the swab as Covid-positive. His study said that swab was the only one that had substantial amounts of raccoon dog genetic material with any traces of the virus.Some scientists, though, said Dr. Bloom’s analysis risked dismissing other Covid-positive swabs by setting too high of a bar for the amount of animal genetic material in a sample.Dr. Bushman, of the University of Pennsylvania, said that the threshold used in the analysis was “aggressive” and that it was best to compare results obtained from a series of different cutoffs.Using a more sensitive threshold, the international team of scientists identified multiple Covid-positive samples containing raccoon dog genetic material, as well as others with genetic signatures of different animals thought to be susceptible to the virus.Alexander Crits-Christoph, a computational biologist formerly at Johns Hopkins University who helped lead the international team’s analysis, said the team also looked closely at whether the Chinese researchers had been right to describe the swab from the cart as positive for the virus.He noted that a number of other swabs from the same stall were clearly positive for the virus. He said results from sampling elsewhere in the market also indicated that unlike the swab from the cart, most of the truly negative swabs contained no traces of the virus at all.“This is environmental sampling of a virus that is a tiny needle in a haystack,” Dr. Crits-Christoph said.

Scientists from the Chinese C.D.C. confirmed that DNA from raccoon dogs and other animals susceptible to the coronavirus was found at the market in early 2020.Chinese government scientists on Wednesday published a long-awaited study about a market in the city of Wuhan, acknowledging that animals susceptible to the coronavirus were there around the time the virus emerged. But the scientists also said that it remained unclear how the pandemic began.The study, published in the journal Nature, focused on swabs taken from surfaces in early 2020 at the Huanan Seafood Wholesale Market, a large market where many of the earliest known Covid patients had worked or shopped. The Chinese scientists had posted an early version of their genetic analysis of those samples in February 2022, but at the time downplayed the possibility of animal infections at the market.The scientists, many of whom are affiliated with the Chinese Center for Disease Control and Prevention, also wanted to publish their data in a peer-reviewed journal. And as part of that process, the scientists uploaded more genetic sequence data to a large international database, the administrators of the database said last month.A few weeks after the data became public, a team of international scientists who had been studying the origins of the pandemic said they stumbled upon the sequences. They found that samples testing positive for the coronavirus contained genetic material belonging to animals, including large amounts that were a match for the raccoon dog, a fluffy mammal sold for fur and meat that was known to be able to spread the coronavirus.That analysis, the subject of a report posted online in late March, did not prove that a raccoon dog itself was infected or that animals gave the virus to people. But it established that raccoon dogs deposited their genetic signatures in the same place where genetic material from the virus was left.Many virologists said that scenario was consistent with one in which the virus spilled into people from an illegally traded wild animal at the market.It appeared that the international team’s analysis sped up the release of the Chinese scientists’ study about the same data: The article appeared on Wednesday on Nature’s website with a note saying that it had been accepted for publication, but was still an “early version” and had not yet been edited.Several authors of the article affiliated with the Chinese C.D.C., William J. Liu, George Gao and Guizhen Wu, did not respond to requests for comment.In their first version of the article from February 2022, the Chinese authors did not mention finding any genetic material from raccoon dogs in the market swabs, which were taken from walls, floors, metal cages and carts. Beyond that, they said that the data did not point to any infected animals.But in Wednesday’s version a little more than a year later, they wrote that the study “confirmed the existence of raccoon dogs” and other animals susceptible to the coronavirus at the market.Many scientists believe that the existing evidence points to those animals likely acting as so-called intermediate hosts for the virus, which probably originated in bats. But they also say the evidence does not completely rule out a scenario in which people gave the virus to animals at the market.The Chinese authors stressed that uncertainty in the new study. They also raised the notion that the virus could have been ferried to the Wuhan market on packages of frozen food, also known as cold chain products. Many scientists consider that scenario highly improbable, but China has promoted it because it gives credence to the idea that the pandemic could have started outside of the country and arrived via imported foods.“The possibility of potential introduction of the virus to the market through infected humans, or cold chain products, cannot be ruled out yet,” the article said.The study included several other unlikely findings as well, outside scientists said in interviews on Wednesday. For example, it said that the swabs contained genetic material from a number of animals that were almost certainly not present at the market, including pandas, chimpanzees and mole-rats.Alice Hughes, an associate professor at the University of Hong Kong focused on conservation biology, said that the inclusion of those animals suggested either that the authors had incorrectly categorized the genetic material or that the samples were contaminated during sequencing in a lab.“This paper’s greatest asset is the fact that it releases a data set for other scientists to analyze more carefully and responsibly,” Dr. Hughes said. “Given the glaring errors in this analysis, the analysis has not been done in a way that’s careful enough to have confidence in any of the results.”Asked how Nature’s peer-review process had treated the species findings, a spokesman for the journal noted that the authors included a caveat that the list of species identified at the market was “not definitive” and more analysis was required.For the international scientists who had first reported finding signs of raccoon dogs in the Covid-positive swabs last month, the latest Nature study left a number of important questions unanswered about the methods used by the Chinese team to analyze the sequences.Still, the publication, as well as an earlier version of it posted online by the Chinese scientists last week, did supply critical new data, including the number of swabs taken from each stall in the market, said Alexander Crits-Christoph, a former postdoctoral researcher and computational biologist at Johns Hopkins University who helped lead the international team’s analysis.With that information, Dr. Crits-Christoph said that he and his collaborators were able to confirm an important finding: Swabs taken from a corner of the market selling wild animals were more likely to test positive for the virus, a result that could not be explained merely by Chinese researchers having taken more samples from that corner, he said.“It’s an extremely impressive data set and its importance is quite high,” Dr. Crits-Christoph said of the market samples. “And because of that, I think it’s a good thing this data has been published in the scientific record, even if I don’t agree with every interpretation.”

In a much-anticipated study, experts described a swab that contained loads of genetic material from the coronavirus and raccoon dogs.On Jan. 12, 2020, Chinese investigators combing a market for clues about the outbreak of a mysterious new illness in the city of Wuhan swabbed a cart. It was the kind typically used for transporting animal cages, and it came back positive for the coronavirus.Three years later, a team of international experts has sifted through the genetic contents of that swab, which were quietly uploaded to an international database and made public only this year. In a report released on Monday night, the scientists described in detail for the first time evidence from the swab that they say strengthens the case that illegally traded wild animals ignited the coronavirus pandemic.Chinese researchers who had originally uploaded the raw data had it removed from the database after they were contacted by the international team. Now administrators of the database itself have cut off access to the international scientists for what they said were rules violations, raising questions about the database’s own role in the tug of war over access to data that could shed light the origins of a virus that has killed seven million people.Along with genetic signatures of the coronavirus, the swab from the cart contained more than 4,500 lengthy fragments of genetic material from raccoon dogs, the report said. It had none from humans. Some Covid-positive swabs taken from other objects and surfaces at the market, the report said, also had more genetic material from animals than from humans.Finding genetic footprints from animals in the same place as genetic material from the virus does not prove that the animals themselves were infected. But some scientists who reviewed the report said that the dominance of genetic material from animals — and especially raccoon dogs — suggested that species known to be able to spread the coronavirus were indeed carrying infections at the market in late 2019.That scenario, they said, was consistent with the virus spilling into humans from market animals and touching off the pandemic, a set of circumstances similar to the one that gave rise to the first SARS outbreak in China two decades earlier.“You look at them and say those are probably infected animals,” Theodora Hatziioannou, a virologist at The Rockefeller University in New York who was not involved in the research, said of the latest findings. “If it was a human shedding the virus, one would expect to find human DNA there, too.”The swabs could yet hold more clues about where the virus in the samples had come from. The report said, for instance, that there was evidence of particular genes that could suggest the material had come from a raccoon dog’s upper respiratory tract.Even if an animal had been infected, however, it would not be clear that it had spread the virus to people. Someone infected with the virus could have gotten a market animal sick. And only by swabbing animals directly could scientists prove whether they had been carrying the virus, a step that was precluded by the market being cleared of animals soon after the outbreak began.The report has been the subject of intense speculation since the international experts presented their findings to the World Health Organization last week and then raced to compile their analyses. At the same time, the findings set off a battle for access to the genetic sequences at their heart.Chinese scientists had initially uploaded the raw sequences to a global database some time after publishing a study describing them last year. But once the international experts discovered the data in early March and alerted Chinese researchers to what they had found, the data was taken offline.Last week, the W.H.O. rebuked China for hiding such crucial information from the rest of the world for three years. Now the nonprofit organization based in Munich that runs the database, called GISAID, has come under scrutiny for its role in controlling access to the data.In the new report, the international team of scientists said that GISAID had “deviated from its stated mission” in allowing the Chinese researchers to withhold the data for so long.The database administrators responded to the report on Tuesday by cutting off the team members’ access to their online accounts and saying that they had violated its rules by getting out ahead of the Chinese scientists and posting their own analysis. The scientists said that they hewed to GISAID’s database-access agreement in downloading and studying the sequences, and noted that they had made multiple offers to work with the Chinese scientists.“The ramifications of cutting off access to this group of authors are huge,” said Michael Worobey, an evolutionary biologist at the University of Arizona and co-author of the new report, noting that GISAID also jeopardized work by team members related to coronavirus variants and flu preparedness. “They’re making false accusations.”The international team homed in on raccoon dogs — fluffy mammals related to foxes and sold for meat and fur — because of how much of the animals’ genetic material was found in the key swab from the cart and because they are known to spread the virus. They said their findings were consistent with that animal harboring the virus, which originated in bats, and passing it to humans at the market.“This isn’t an infected animal,” said Joel Wertheim, a virologist at the University of California, San Diego and a co-author of the report, referring to the new genetic data. “But this is the closest you can get without having the animal in front of you.”The report, though, also offered the most concrete evidence to date of other animals susceptible to the virus being sold at the market, noted Kristian Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., and a co-author of the report. Genetic material from those animals — like the masked palm civet, a small Asian mammal that was implicated in the SARS outbreak two decades ago — was also found in swabs that were positive for the coronavirus.“It’s literally Disney Land for zoonotic transfer,” said Joseph DeRisi, a professor of biochemistry at the University of California, San Francisco, and co-president of the Chan Zuckerberg Biohub, referring to the range of animals documented in the report.A number of other swabs at the market found large quantities of human genetic material — an indication, the report said, of certain virus samples likely being shed by infected people. Many of the earliest known Covid patients worked or shopped at the market.Still other positive swabs, the report said, were dominated by genetic material from animals that are not believed to be susceptible to the virus. A sample taken from a fish packaging surface, for example, contained a lot of fish genetic material. That virus was likely to have been deposited by a person, scientists said, illustrating that substantial amounts of animal genetic material did not necessarily mean that animals had produced the virus there.Citing those findings, some scientists said that the kinds of swabs analyzed in the report simply could not offer conclusive proof of an infected animal.“The report does contain useful information,” Sergei Pond, a virologist at Temple University in Philadelphia, said. But, he added, “Does it tell you anything about which animal was infected? It really doesn’t.”Dr. David Relman, a microbiologist at Stanford, said that it was difficult to assess the findings without more details about how the Chinese investigators had collected and analyzed their swabs. The Chinese paper last year, he noted, described using a kit to filter out human genetic material and make the tests more sensitive to the virus.But a number of swabs from the Chinese researchers described in the international team’s report contained substantial amounts of human genetic material, suggesting that those filtering methods had not depleted the samples of human material. Dr. DeRisi, who specializes in the type of analysis described in the report, said that such kits were generally ineffective at removing the genetic signatures of people.Frederic Bushman, a microbiologist at the University of Pennsylvania who also specializes in sequencing techniques, agreed that the report’s methods were sound.“I think the simplest explanation is that it’s an infected raccoon dog,” he said. “I don’t think it’s absolute proof.”

Genetic research from China suggests to some experts that the coronavirus may have sprung from a market in Wuhan. Now the data are missing from a scientific database.The World Health Organization rebuked Chinese officials on Friday for withholding research that may link Covid’s origin to wild animals, asking why the data had not been made available three years ago and why it is now missing.Before the Chinese data disappeared, an international team of virus experts downloaded and began analyzing the research, which appeared online in January. They say it supports the idea that the pandemic could have begun when illegally traded raccoon dogs infected humans at a Wuhan seafood market.But the gene sequences were removed from a scientific database once the experts offered to collaborate on the analysis with their Chinese counterparts.“These data could have — and should have — been shared three years ago,” Dr. Tedros Adhanom Ghebreyesus, the W.H.O.’s director general, said. The missing evidence now “needs to be shared with the international community immediately,” he said.According to the experts who are reviewing it, the research offers evidence that raccoon dogs, fox-like animals known to spread coronaviruses, had left behind DNA in the same place in the Wuhan market that genetic signatures of the new coronavirus also were discovered.To some experts, that finding suggests that the animals may have been infected and may have transmitted the virus to humans.With huge amounts of genetic information drawn from swabs of animal cages, carts and other surfaces at the Wuhan market in early 2020, the genetic data had been the focus of restless anticipation among virus experts since they learned of it a year ago in a paper by Chinese scientists.A French biologist discovered the genetic sequences in the database last week, and she and a team of colleagues began mining them for clues about the origins of the pandemic.That team has not yet released a paper outlining the findings. But the researchers delivered an analysis of the material to a W.H.O. advisory group studying Covid’s origins this week in a meeting that also included a presentation by Chinese researchers regarding the same data.“These data could have — and should have — been shared three years ago,” Dr. Tedros Adhanom Ghebreyesus, the W.H.O.’s director general, said. Cyril Zingaro/EPA, via ShutterstockThe analysis seemed to clash with earlier contentions by Chinese scientists that samples taken in the market that were positive for the coronavirus had been ferried in by sick people alone, said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago who was not involved in the latest analysis.“It’s just very unlikely to be seeing this much animal DNA, especially raccoon dog DNA, mixed in with viral samples, if it’s simply mostly human contamination,” Dr. Cobey said.Questions remain about how the samples were collected, what precisely they contained and why the evidence had disappeared. In light of the ambiguities, many scientists reacted cautiously, saying that it was difficult to assess the research without seeing a complete report.The idea that a lab accident could have accidentally set off the pandemic has become the focus of renewed interest in recent weeks, thanks in part to a fresh intelligence assessment from the Department of Energy and hearings led by the new Republican House leadership.But a number of virus experts not involved with the latest analysis said that what was known about the swabs gathered in the market buttressed the case that animals sold there had sparked the pandemic.“It’s exactly what you’d expect if the virus was emerging from an intermediate or multiple intermediate hosts in the market,” Dr. Cobey said. “I think ecologically, this is close to a closed case.”Dr. Cobey was one of 18 scientists who signed an influential letter in the journal Science in May 2021 urging serious consideration of a scenario in which the virus could have spilled out of a laboratory in Wuhan.On Friday, she said lab leaks continued to pose enormous risks and that more oversight of research into dangerous pathogens was needed. But Dr. Cobey added that an accumulation of evidence — relating to the clustering of human cases around the Wuhan market, the genetic diversity of viruses there, and now the raccoon dog data — strengthened the case for a market origin.The new genetic data do not appear to prove that a raccoon dog was infected with the coronavirus. Even if it had been, the possibility would remain that another animal could have passed that virus to people, or even that someone infected with the virus could have transmitted it to a raccoon dog.Some scientists stressed those points on Friday, saying that the new genetic data did not appreciably shift the discussion about the pandemic’s origins.“We know it’s a promiscuous virus that infects a bunch of species,” said David Fisman, an epidemiologist at the University of Toronto, who also signed the May 2021 letter in Science.Chinese scientists had released a study in February 2022 looking at the market samples. Some scientists speculated that the Chinese researchers might have posted the data in January because they were required to make them available as part of a review of their study by a scientific journal.The Chinese study had suggested that samples that were positive for the virus had come from infected people, rather than from animals sold in the market. That fit with a narrative long promulgated by Chinese officials: that the virus sprang not only from outside the market, but also from outside the country altogether.But the Chinese report had left clues that viral material at the market had been jumbled together with genetic material from animals. And scientists said that the new analysis by the international team illustrated an even stronger link with animals.“Scientifically, it doesn’t prove that raccoon dogs were the source, but it sure smells like infected raccoon dogs were at the market,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport.He added, “It raises more questions about what the Chinese government really knows.”Scientists cautioned that it was not clear that the genetic material from the virus and from raccoon dogs had been deposited at the same time.Depending on the stability of genetic material from the virus and the animals, said Michael Imperiale, a virologist at the University of Michigan, “they could have been deposited there at potentially widely different times.”Still, Dr. Arturo Casadevall, an immunologist at the Johns Hopkins Bloomberg School of Public Health who co-authored a recent study with Dr. Imperiale examining the origin of the coronavirus, said that linking animal and viral material nevertheless added to the evidence of a natural spillover event.“I would say it strengthens the zoonotic idea,” he said, “that is, the idea that it came from an animal at the market.”In the absence of the actual animal that first spread the virus to people, Dr. Casadevall said, assessing the origins of an outbreak would always involve weighing probabilities. In this case, animals sold at the market were removed before researchers began taking samples in early 2020, making it impossible to find a culprit.Tim Stearns, the dean of graduate and postgraduate studies at the Rockefeller University in New York, said that the latest finding was “an interesting piece of the puzzle,” though he said it was “not in itself definitive and highlights the need for a more thorough investigation.”For all the missing elements, some scientists said that the new findings highlighted just how much information scientists had managed to assemble about the beginnings of the pandemic, including home addresses for early patients and sequence data from the market.Theodora Hatziioannou, a virologist at the Rockefeller University, said that it was critical that the raw data be released. But, she said, “I think the evidence is overwhelming at the moment toward a market origin.”And the latest data, she said, “makes it even more unlikely that this started somewhere else.”Felicia Goodrum, an immunobiologist at the University of Arizona, said that finding the virus in an actual animal would be the strongest evidence of a market origin. But finding virus and animal material in the same swab was close.“To me,” she said, “this is the next best thing.”