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Tag: SARS-CoV-2

  • Virus that causes COVID widespread in wildlife, Virginia Tech researchers say – WTOP News

    Virus that causes COVID widespread in wildlife, Virginia Tech researchers say – WTOP News

    The virus that causes COVID-19 has been spreading through Virginia wildlife, and Virginia Tech researchers say well-populated areas are likely where it spread from humans to animals.

    The virus that causes COVID-19 has been spreading through Virginia wildlife, and Virginia Tech researchers say well-populated areas are likely where it spread from humans to animals.

    While SARS-CoV-2 infections were previously identified in wildlife, primarily in white-tailed deer and feral mink, Virginia Tech researchers attempted to see whether the virus had spread to common backyard wildlife.

    Researcher Carla Finkielstein, who is also director of the Virginia Tech Molecular Diagnostics Lab, said tracking the spread of the virus is important.

    “The more we get vaccinated and protected, the higher the chances that the virus will try to find a new host,” Finkielstein said. “The virus is indifferent to whether its host walks on two legs or four — its primary objective is survival.”

    The research team collected 798 nasal and oral swabs across Virginia from animals that were either live-trapped in the field and released, or were being treated in wildlife rehabilitation centers.

    The team obtained 126 blood sample from six species. The study also identified two mice at the same site on the same day with the exact same variant, suggesting they either both got it from the same human, or one mouse infected the other.

    Finkielstein said it’s not clear how the virus was transmitted from humans to wildlife.

    “The most reasonable speculations are trash, food residues, wastewater,” she said. “Something that we humans infected, discarded or disposed of, and then the animals picked it up.”

    When asked whether there was any indication that animals could also spread COVID to humans, she said, “We don’t have evidences of the other way around.”

    The team will continue its research supported by a $5 million grant from the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, in part to understand how the virus’ presence in wildlife may influence the long-term maintenance of COVID in humans.

    “We shouldn’t be afraid of wildlife or interacting with wildlife,” Finkielstein said. “We just need to be mindful of how we do this.”

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    Neal Augenstein

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  • Why Are We Still Flu-ifying COVID?

    Why Are We Still Flu-ifying COVID?

    Four years after what was once the “novel coronavirus” was declared a pandemic, COVID remains the most dangerous infectious respiratory illness regularly circulating in the U.S. But a glance at the United States’ most prominent COVID policies can give the impression that the disease is just another seasonal flu. COVID vaccines are now reformulated annually, and recommended in the autumn for everyone over the age of six months, just like flu shots; tests and treatments for the disease are steadily being commercialized, like our armamentarium against flu. And the CDC is reportedly considering more flu-esque isolation guidance for COVID: Stay home ’til you’re feeling better and are, for at least a day, fever-free without meds.

    These changes are a stark departure from the earliest days of the crisis, when public-health experts excoriated public figures—among them, former President Donald Trump—for evoking flu to minimize COVID deaths and dismiss mitigation strategies. COVID might still carry a bigger burden than flu, but COVID policies are getting more flu-ified.

    Read: The flu-ification of COVID policy is almost complete

    In some ways, as the population’s immunity has increased, COVID has become more flu-like, says Roby Bhattacharyya, a microbiologist and an infectious-disease physician at Massachusetts General Hospital. Every winter seems to bring a COVID peak, but the virus is now much less likely to hospitalize or kill us, and somewhat less likely to cause long-term illness. People develop symptoms sooner after infection, and, especially if they’re vaccinated, are less likely to be as sick for as long. COVID patients are no longer overwhelming hospitals; those who do develop severe COVID tend to be those made more vulnerable by age or other health issues.

    Even so, COVID and the flu are nowhere near the same. SARS-CoV-2 still spikes in non-winter seasons and simmers throughout the rest of the year. In 2023, COVID hospitalized more than 900,000 Americans and killed 75,000; the worst flu season of the past decade hospitalized 200,000 fewer people and resulted in 23,000 fewer deaths. A recent CDC survey reported that more than 5 percent of American adults are currently experiencing long COVID, which cannot be fully prevented by vaccination or treatment, and for which there is no cure. Plus, scientists simply understand much less about the coronavirus than flu viruses. Its patterns of spread, its evolution, and the durability of our immunity against it all may continue to change.

    And yet, the CDC and White House continue to fold COVID in with other long-standing seasonal respiratory infections. When the nation’s authorities start to match the precautions taken against COVID with those for flu, RSV, or common colds, it implies “that the risks are the same,” Saskia Popescu, an epidemiologist at the University of Maryland, told me. Some of those decisions are “not completely unreasonable,” says Costi Sifri, the director of hospital epidemiology at UVA Health, especially on a case-by-case basis. But taken together, they show how bent America has been on treating COVID as a run-of-the-mill disease—making it impossible to manage the illness whose devastation has defined the 2020s.

    Each “not completely unreasonable” decision has trade-offs. Piggybacking COVID vaccines onto flu shots, for instance, is convenient: Although COVID-vaccination rates still lag those of flu, they might be even lower if no one could predict when shots might show up. But such convenience may come at the cost of protecting Americans against COVID’s year-round threat. Michael Osterholm, an epidemiologist at the University of Minnesota School of Public Health, told me that a once-a-year vaccine policy is “dead wrong … There is no damn evidence this is a seasonal virus yet.” Safeguards against infection and milder illness start to fade within months, leaving people who dose up in autumn potentially more susceptible to exposures by spring. That said, experts are still torn on the benefits of administering the same vaccine more than once a year—especially to a public that’s largely unwilling to get it. Throughout the pandemic, immunocompromised people have been able to get extra shots. And today, an advisory committee to the CDC voted to recommend that older adults once again get an additional dose of the most recently updated COVID vaccine in the coming months. Neither is a pattern that flu vaccines follow.

    Read: Fall’s vaccine routine didn’t have to be this hard

    Dropping the current COVID-isolation guideline—which has, since the end of 2021, recommended that people cloister for five days—may likewise be dangerous. Many Americans have long abandoned this isolation timeline, but given how new COVID is to both humanity and science, symptoms alone don’t yet seem enough to determine when mingling is safe, Popescu said. (The dangers are even tougher to gauge for infected people who never develop fevers or other symptoms at all.) Researchers don’t currently have a clear picture of how long people can transmit the virus once they get sick, Sifri told me. For most respiratory illnesses, fevers show up relatively early in infection, which is generally when people pose the most transmission risk, says Aubree Gordon, an epidemiologist at the University of Michigan. But although SARS-CoV-2 adheres to this same rough timeline, infected people can shed the virus after their symptoms begin to resolve and are “definitely shedding longer than what you would usually see for flu,” Gordon told me. (Asked about the specifics and precise timing of the update, a CDC spokesperson told me that there were “no updates to COVID guidelines to announce at this time,” and did not respond to questions about how flu precedents had influenced new recommendations.)

    At the very least, Emily Landon, an infectious-disease physician at the University of Chicago, told me, recommendations for all respiratory illnesses should tell freshly de-isolated people to mask for several days when they’re around others indoors; she would support some change to isolation recommendations with this caveat. But if the CDC aligns the policy fully with its flu policy, it might not mention masking at all.

    Read: No one really knows how much COVID is silently spreading … again

    Several experts told me symptom-based isolation might also remove remaining incentives to test for the coronavirus: There’s little point if the guidelines for all respiratory illnesses are essentially the same. To be fair, Americans have already been testing less frequently—in some cases, to avoid COVID-specific requirements to stay away from work or school. And Osterholm and Gordon told me that, at this point in the pandemic, they agree that keeping people at home for five days isn’t sustainable—especially without paid sick leave, and particularly not for health-care workers, who are in short supply during the height of respiratory-virus season.

    But the less people test, the less they’ll be diagnosed—and the less they’ll benefit from antivirals such as Paxlovid, which work best when administered early. Sifri worries that this pattern could yield another parallel to flu, for which many providers hesitate to prescribe Tamiflu, debating its effectiveness. Paxlovid use is already shaky; both antivirals may end up chronically underutilized.

    Flu-ification also threatens to further stigmatize long COVID. Other respiratory infections, including flu, have been documented triggering long-term illness, but potentially at lower rates, and to different degrees than SARS-CoV-2 currently does. Folding this new virus in with the rest could make long COVID seem all the more negligible. What’s more, fewer tests and fewer COVID diagnoses could make it much harder to connect any chronic symptoms to this coronavirus, keeping patients out of long-COVID clinics—or reinforcing a false portrait of the condition’s rarity.

    The U.S. does continue to treat COVID differently from flu in a few ways. Certain COVID products remain more available; some precautions in health-care settings remain stricter. But these differences, too, will likely continue to fade, even as COVID’s burden persists. Tests, vaccines, and treatments are slowly commercializing; as demand for them drops, supply may too. And several experts told me that they wouldn’t be surprised if hospitals, too, soon flu-ify their COVID policies even more, for instance by allowing recently infected employees to return to work once they’re fever-free.

    Early in the pandemic, public-health experts hoped that COVID’s tragedies would prompt a rethinking of all respiratory illnesses. The pandemic showed what mitigations could do: During the first year of the crisis, isolation, masking, distancing, and shutdowns brought flu transmission to a near halt, and may have driven an entire lineage of the virus to extinction—something “that never, in my wildest dreams, did I ever think would be possible,” Landon told me.

    Most of those measures weren’t sustainable. But America’s leaders blew right past a middle ground. The U.S. could have built and maintained systems in which everyone had free access to treatments, tests, and vaccines for a longer list of pathogens; it might have invested in widespread ventilation improvements, or enacted universal sick leave. American homes might have been stocked with tests for a multitude of infectious microbes, and masks to wear when people started to cough. Vaccine requirements in health-care settings and schools might have expanded. Instead, “we seem to be in a more 2019-like place than a future where we’re preventing giving each other colds as much as we could,” Bhattacharyya told me.

    Read: Next winter, what if we test for even more viruses?

    That means a return to a world in which tens of thousands of Americans die each year of flu and RSV, as they did in the 2010s. With COVID here to stay, every winter for the foreseeable future will layer on yet another respiratory virus—and a particularly deadly, disabling, and transmissible one at that. The math is simple: “The risk has overall increased for everyone,” Landon said. That straightforward addition could have inspired us to expand our capacity for preserving health and life. Instead, our tolerance for suffering seems to be the only thing that’s grown.

    Katherine J. Wu

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  • Bats Could Hold the Secret to Better, Longer Human Life

    Bats Could Hold the Secret to Better, Longer Human Life

    In Linfa Wang’s ideal world, all humans would be just a bit more bat-like.

    Wang, a biochemist and zoonotic-disease expert at Duke-NUS Medical School, in Singapore, has no illusions about people flapping about the skies or echolocating to find the best burger in town. The point is “not to live like a bat,” Wang told me, but to take inspiration from their very weird physiology in order to boost the quality, or even the length, of human life. They might not look it, but bats, Wang said, are “the healthiest mammals on Earth.”

    That thought might be tough to square with bats’ recent track record. In the past three decades—from 1994, when Hendra virus jumped to humans, to 2019, when SARS-CoV-2 emerged—at least half a dozen of the most devastating viral epidemics known to have recently leapt into people from wildlife have had their likeliest origins in bats. But bats themselves rarely, if ever, seem to fall ill. Ebola, Nipah, Marburg, and various coronaviruses don’t appear to trouble them; some bats can survive encounters with rabies, which, left untreated in humans, has a near 100 percent fatality rate. “They’ve evolved mechanisms to limit the damage of disease,” says Emma Teeling, a bat biologist at University College Dublin, who collaborates with Wang.

    Read: Why we’re afraid of bats

    The creatures’ apparent ability to defy death goes even beyond that. Some nectar-devouring species spend years spiking their blood-sugar levels high enough to send a human into a hyperglycemic coma—and yet, those bats never seem to develop what we’d call diabetes. Others have been documented surviving up to 41 years in the wild—nearly 10 times as long as mammals of their size are generally expected to live—all the while avoiding cancer and fertility dips.

    Wang and Teeling, along with several colleagues, were recently awarded a $13 million grant by the European Research Council to try to better understand the biology behind these batty abilities—and how it might help other creatures. (And they’re certainly not the only ones trying to find out.) Wang’s team, as he likes to cheerfully boast, has already put some of his ideas to the test by genetically engineering a healthier, more disease-tolerant “bat-mouse.” He and his colleagues are still years away from creating any sort of bat person, but they are confident that this line of thinking could one day inform new treatments for humans—to combat diabetes, to temper infectious diseases, maybe even to extend the life span.

    The key to bats’ health seems to be flight, or at least the effects that evolving flight has had on the bat body. Flight, for all its perks, is one of the most energetically taxing transportation options: When bats fly, their metabolism can rev up to 15 to 16 times above its resting state; their heart rate may soar above 1,000 beats per minute; their body temperature can exceed 105 degrees Fahrenheit, effectively plunging the animals into an epic fever state. Put all of that on virtually any other mammal, and their body would likely be overwhelmed by the blaze of extreme inflammation, the toxic by-products of their metabolism effectively rending cells apart.

    To cope with this self-destructive form of locomotion, bats have evolved two essential safeguards. First, they are extraordinarily good at maintaining bodily Zen. Even when pushed into extreme forms of exertion, bat bodies don’t get all that inflamed—maybe in part because they lack some of the molecular machinery that kicks those systems into gear. Which means that bats simply rack up less damage when their bodies get stressed. And for any damage that does occur, bats have a second trick: Their cells appear to be unusually efficient at cleanup and repair, rapidly stitching back together bits of torn-up DNA.

    Those strategies, Wang and Teeling told me, haven’t just made flight a breeze for bats. They also mitigate other types of bodily harm. Cancer tends to unfurl after errors appear in particular parts of our genetic code. And, molecularly speaking, aging is basically what happens to the body as it accumulates a lifetime of cellular wear and tear. In a sense, stress is simply stress: The root causes of these chronic health issues overlap with the greatest taxes of flight. So the solutions that keep a bat body running smoothly in the air can address problems throughout its lifetime. While humans get worse at repairing damage with age, bats’ ability improves, Teeling told me.

    All of this can also help explain why bats are such hospitable hosts for pathogens that can kill us. Many of the most dangerous cases of infectious disease are driven by the body’s overzealous inflammatory response; that reaction can pose a greater threat than any damage that a pathogen itself might do to cells. Many of our defenses are like bombs set off on our home turf—capable of killing invaders, yes, but at great cost to us. Bats have such a high threshold for igniting inflammation that many viruses seem able to inhabit their tissues without setting off that degree of destruction. In laboratory experiments, bats have been dosed with so much virus that their tissues end up chock-full—clocking some 10 million units of Ebola virus per milliliter of serum, or 10 million units of the MERS coronavirus per gram of lung——and researchers were still unable to discern serious problems with the bats’ health. Bats and their viruses have, in effect, struck “an immunological detente,” says Tony Schountz, a bat immunologist at Colorado State University.

    Such astronomical levels of virus aren’t a bat’s preferred state. Bat bodies also happen to be very good at tamping down viral replication up front. Part of the reason seems to be that, in certain bat species’ bodies, parts of their antiviral defense system “are always on,” Wang told me. “I call them ‘battle ready.’” So when a pathogen does appear, it knocks up against a host that is already teeming with powerful proteins, ready-made to block parts of the viral life cycle, hindering the microbe from spinning out of control.

    The catch here is that the viruses have wised up to bats’ tricks—and evolved to be more forceful as they attempt to infiltrate and replicate inside of, and then spread between, those well-defended cells. And that bat-caliber offense can be excessive in a human that lacks the same shields, says Cara Brook, a disease ecologist at the University of Chicago. That might help explain why so many bat viruses hit us so hard.. Couple that show of force with our difficulties reining in our own inflammation, and what might have been a trivial infection for a bat can turn into utter chaos for a person.

    One of Wang’s primary ideas for dealing with this kind of host-pathogen mismatch is to use drugs to make our inflammatory responses a bit more muted—that is, a bit more bat-like. That option is especially intriguing, he told me, because it could also lower the risk of autoimmunity, maybe even forestall aging or certain kinds of chronic metabolic disease. His bat-mouse, which was engineered to express a particular inflammation-suppressing bat gene, is an experiment with that principle, and it seemed to fare better against flu, SARS-CoV-2, even gout crystals.

    Read: Hibernation: the extreme lifestyle that can stop aging

    But the idea of muffling inflammation isn’t exactly new: Our medical armamentarium has included steroids and other immune-system-modulating drugs for decades. All have their limits and their drawbacks, and a treatment specifically inspired by bats would likely be subject to the same caveats, says Arinjay Banerjee, a virologist and bat immunologist at the University of Saskatchewan. Inflammation, as damaging as it can be, is an essential defense. Any drug that modifies it—especially one taken long-term—must avoid the hurt of too much while skirting the risk of not enough. And ultimately, humans just aren’t bats. Plop a bat’s defense into a human body, and it might not work in the way researchers expect, says Hannah Frank, a bat immunologist at Tulane University. To truly see bat-like benefits in people, chances are, we’d need more than one treatment turning more than one physiological dial, Banerjee told me.

    As much as researchers are learning about bats, the gaps in their knowledge are still huge. What’s observed in one of the more than 1,400 species of bats may not hold true for another. Plus, bat physiology is distinct enough from ours that no one really can precisely say what optimal health for them looks like, Frank told me. Although bats rarely die from their viruses, those infections may be still taking a toll in ways that researchers have yet to appreciate, Brook told me. Bats aren’t the only intriguing virus-carriers, either. Rodents, too, haul around a lot of deadly pathogens without falling sick, as Schountz points out. Nor are they the only mammals that live at extremes. Naked mole rats withstand low-oxygen conditions underground; seals must cope with organ-crushing pressures when they dive. Like flight, those adaptations may have rejiggered immunity in yet untold ways.

    Certainly, though, bats have more to offer us than many people give them credit for. In the aftermath of a Hendra virus outbreak in Australia, years ago, “we even had a politician say, Let’s bomb the bats,” Wang told me. The start of the coronavirus pandemic, too, ignited calls for bat cullings; some animals were even reportedly burned out of roosts. “I still don’t want a bat as a pet,” Wang told me. But if his findings keep panning out, maybe someday people will associate bats less with the diseases we don’t want to get from them, and more with the healthy traits we do.

    Katherine J. Wu

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  • One More COVID Summer?

    One More COVID Summer?

    Since the pandemic’s earliest days, epidemiologists have been waiting for the coronavirus to finally snap out of its pan-season spree. No more spring waves like the first to hit the United States in 2020, no more mid-year surges like the one that turned Hot Vax Summer on its head. Eventually, or so the hope went, SARS-CoV-2 would adhere to the same calendar that many other airway pathogens stick to, at least in temperate parts of the globe: a heavy winter peak, then a summer on sabbatical.

    But three and a half years into the outbreak, the coronavirus is still stubbornly refusing to take the warmest months off. Some public-health experts are now worried that, after a relatively quiet stretch, the virus is kick-starting yet another summer wave. In the southern and northeastern United States, concentrations of the coronavirus in wastewater have been slowly ticking up for several weeks, with the Midwest and West now following suit; test-positivity rates, emergency-department diagnoses of COVID-19, and COVID hospitalizations are also on the rise. The absolute numbers are still small, and they may stay that way. But these are the clear and early signs of a brewing mid-year wave, says Caitlin Rivers, an epidemiologist at Johns Hopkins University—which would make this the fourth summer in a row with a distinct coronavirus bump.

    Even this far into the pandemic, though, no one can say for certain whether summer waves are a permanent COVID fixture—or if the virus exhibits a predictable seasonal pattern at all. No law of nature dictates that winters must come with respiratory illness, or that summers will not. “We just don’t know very much about what drives the cyclical patterns of respiratory infections,” says Sam Scarpino, an infectious-disease modeler at Northeastern University. Which means there’s still no part of the year when this virus is guaranteed to cut us any slack.

    That many pathogens do wax and wane with the seasons is indisputable. In temperate parts of the world, airborne bugs get a boost in winter, only to be stifled in the heat; polio and other feces-borne pathogens, meanwhile, often rise in summer, along with gonorrhea and some other STIs. But noticing these trends is one thing; truly understanding the triggers is another.

    Read: COVID sure looks seasonal now

    Some diseases lend themselves a bit more easily to explanation: Near the equator, waves of mosquito-borne illness, such as Zika and Chikungunya, tend to be tied to the weather-dependent life cycles of the insects that carry them; in temperate parts of the world, rates of Lyme disease track with the summertime activity of ticks. Flu, too, has pretty strong data to back its preference for wintry months. The virus—which is sheathed in a fragile, fatty layer called an envelope and travels airborne via moist drops—spreads best when it’s cool and dry, conditions that may help keep infectious particles intact and spittle aloft.

    The coronavirus has enough similarities to flu that most experts expect that it will continue to spread in winter too. Both viruses are housed in a sensitive skin; both prefer to move by aerosol. Both are also relatively speedy evolvers that don’t tend to generate long-lasting immunity against infection—factors conducive to repeat waves that hit populations at a fairly stable clip. For those reasons, Anice Lowen, a virologist at Emory University, anticipates that SARS-CoV-2 will continue to show “a clear wintertime seasonality in temperate regions of the world.” Winter is also a time when our bodies can be more susceptible to respiratory bugs: Cold, dry air can interfere with the movement of mucus that shuttles microbes out of the nose and throat; aridity can also make the cells that line those passageways shrivel and die; certain immune defenses might get a bit sleepier, with vitamin D in shorter supply.

    None of that precludes SARS-CoV-2 spread in the heat, even if experts aren’t sure why the virus so easily drives summer waves. Plenty of other microbes manage it: enteroviruses, polio, and more. Even rhinoviruses and adenoviruses, two of the most frequent causes of colds, tend to spread year-round, sometimes showing up in force during the year’s hottest months. (Many scientists presume that has something to do with these viruses’ relatively hardy outer layer, but the reason is undoubtedly more complex than that.) An oft-touted explanation for COVID’s summer waves is that people in certain parts of the country retreat indoors to beat the heat. But that argument alone “is weak,” Lowen told me. In industrialized nations, people spend more than 90 percent of their time indoors.

    That said, an accumulation of many small influences can together create a seasonal tipping point. Summer is a particularly popular time for travel, often to big gatherings. Many months out from winter and its numerous infections and vaccinations, population immunity might also be at a relative low at this time of year, Rivers said. Plus, for all its similarities to the flu, SARS-CoV-2 is its own beast: It has so far affected people more chronically and more severely, and has generated population-sweeping variants at a far faster pace. Those dynamics can all affect when waves manifest.

    And although certain bodily defenses do dip in the cold, data don’t support the idea that immunity is unilaterally stronger in the summer. Micaela Martinez, the director of environmental health at WE ACT for Environmental Justice, in New York, told me the situation is far more complicated than that. For years, she and other researchers have been gathering evidence that suggests that our bodies have distinctly seasonal immunological profiles—with some defensive molecules spiking in the summer and another set in winter. The consequences of those shifts aren’t yet apparent. But some of them could help explain when the coronavirus spreads. By the same token, winter is not a time of disease-ridden doom. Xaquin Castro Dopico, an immunologist at the Karolinska Institute, in Sweden, has found that immune systems in the Northern Hemisphere might be more inflammation-prone in the winter—which, yes, could make certain bouts of illness more severe but could also improve responses to certain vaccinations.

    All of those explanations could apply to COVID’s summer swings—or perhaps none does. “Everybody always wants to have a very simple seasonal answer,” Martinez told me. But one may simply not exist. Even the reasons for the seasonality of polio, a staunch summertime disease prior to its elimination in the U.S., have been “an open question” for many decades, Martinez told me.

    Rivers is hopeful that the coronavirus’s permanent patterns may already be starting to peek through: a wintry heyday, and a smaller maybe-summer hump. “We’re in year four, and we’re seeing the same thing year over year,” she told me. But some experts worry that discussions of COVID-19 seasonality are premature. SARS-CoV-2 is still so fresh to the human population that its patterns could be far from their final form. At an extreme, the patterns researchers observed during the first few years of the pandemic may not prelude the future much at all, because they encapsulate so much change: the initial lack and rapid acquisition of immunity, the virus’s evolution, the ebb and flow of masks, and more. Amid that mishmash of countervailing influences, says Brandon Ogbunu, an infectious-disease modeler at Yale, “you’re going to get some counterintuitive dynamics” that won’t necessarily last long term.

    Read: The next stage of COVID is starting now

    With so much of the world now infected, vaccinated, or both, and COVID mitigations almost entirely gone, the global situation is less in flux now. The virus itself, although still clearly changing at a blistering pace, has not pulled off an Omicron-caliber jump in evolution for more than a year and a half. But no one can yet promise predictability. The cadence of vaccination isn’t yet settled; Scarpino, of Northeastern University, also isn’t ready to dismiss the idea of a viral evolution surprise. Maybe summer waves, to the extent that they’re happening, are a sign that SARS-CoV-2 will remain a microbe for all seasons. Or maybe they’re part of the pandemic’s death rattle—noise in a system that hasn’t yet quieted down.

    Katherine J. Wu

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  • The COVID-Origins Debate Has Split Into Parallel Worlds

    The COVID-Origins Debate Has Split Into Parallel Worlds

    The lab-leak theory of COVID’s origin has always been a little squirrelly. If SARS-CoV-2 really did begin infecting humans in a research setting, the evidence that got left behind is mostly of the cloak-and-dagger type: confirmations from anonymous government officials about vague conclusions drawn in classified documents, for example; or leaked materials that lay out hypothetical research projects; or information gleaned from who-knows-where that certain people came down with who-knows-what disease at some crucial moment. In short, it’s all been messy human stuff, the bits and bobs of intelligence analysis. Simple-seeming facts emerge from a dark matter of sources and methods.

    So it goes again. The latest major revelation in this line emerged this week. Taken at face value, it’s extraordinary: Ben Hu, a high-level researcher at the Wuhan Institute of Virology, and two colleagues, Yu Ping and Yan Zhu, could have been the first people on the planet to be infected with SARS-CoV-2, according to anonymous sources cited first in the newsletter Public and then in The Wall Street Journal. These proposed patient SARS-CoV-zeroes aren’t merely employees of the virology institute; they’re central figures in the very sort of research that lab-leak investigators have been scrutinizing since the start of the pandemic. Their names appear on crucial papers related to the discovery of new, SARS-related coronaviruses in bats, and subsequent experimentation on those viruses. (The Journal reached out to the three researchers, but they did not respond.)

    Is this the “smoking gun,” at last, as many now insist? Has the Case of the Missing COVID Origin finally been solved? If it’s true these were the very first infected people, then their professional activities mean they almost certainly caught the virus in the lab, not a market stall full of marmots and raccoon dogs. The origins debate has from the start revolved around a pair of dueling “coincidences.” The fact that the pandemic just happened to take off at a wet market suggests that the virus spilled over into humans from animals for sale there. But the fact that it also just happened to take off not too far away from one of the world’s leading bat-coronavirus labs suggests the opposite. This week’s information seems to tip the balance very heavily toward the latter interpretation.

    Read: If the lab-leak theory is right, what’s next?

    The only problem is, we don’t know whether the latest revelations can be trusted, or to what extent. The newly reported facts appear to stem from a single item of intelligence, furnished by a foreign source, that has bounced around inside the U.S. government since sometime in 2020. Over the past two and a half years, the full description of the sickened workers in Wuhan has been revealed with excruciating slowness, in sedimenting clauses, through well-timed leaks. This glacial striptease has finally reached its end, but is the underlying information even true? Until that question can be answered (which could be never), the origins debate will be stuck exactly where it’s been for many months: always moving forward, never quite arriving.

    The story of these sickened workers has been in the public domain, one way or another, since the start of 2021. Officials in the Trump administration’s State Department, reportedly determined to go public with their findings, put out a fact sheet about various events and circumstances at the Wuhan Institute of Virology around the beginning of the pandemic. Included was a quick description of alleged illnesses among the staff. The fact sheet didn’t name the sickened scientists or what they did inside the lab, or when exactly their illnesses occurred. It didn’t specify their symptoms, nor did it say how many scientists had gotten sick. If you boiled it down, the fact sheet’s revelations could be paraphrased like this:

    Several researchers at WIV became ill with respiratory symptoms in autumn 2019.

    That vague stub did little to budge consensus views. The lab-leak theory had been preemptively “debunked” in early 2020, and broad disregard of the idea—contempt of it, really—hadn’t yet abated. The day before the State Department fact sheet was released, a team of 17 international experts dispatched by the World Health Organization arrived in Wuhan to conduct (with the help of Chinese scientists) a comprehensive study of the pandemic’s origins. By the time of their return in February 2021, they’d come out with their conclusions: The lab-leak theory was “extremely unlikely” to be true, they said.

    The next month, while the WHO team was preparing to release its final report, further details of the sick-researchers story began to trickle out. In a panel discussion of COVID origins and then in an interview with the Daily Mail, David Asher, a former State Department investigator who’s now a senior fellow at a conservative think tank, filled in a few more specifics, including that the researchers had been working in a coronavirus laboratory and that the wife of one of them later died. The intel had arrived from a foreign government, he said. Now the facts that were revealed could be summarized like so:

    Three coronavirus researchers at WIV became severely ill with respiratory symptoms in the second week of November 2019.

    Pressure for a more serious appraisal of the lab-leak theory grew throughout that spring. In May 2021, more than a dozen prominent virologists and biosafety experts published a letter in the journal Science calling for “a proper investigation” of the matter. A week later, The Wall Street Journal published a leak from anonymous current and former U.S. officials: According to a “previously undisclosed US intelligence report,” the paper said, the sickened researchers had been treated for their sickness at a hospital. In other words, they probably weren’t suffering from common colds. This new aspect of the narrative was making headlines now, like this:

    Three coronavirus researchers at WIV became severely ill with respiratory symptoms in the second week of November 2019 and sought hospital care.

    After all of this publicity, President Joe Biden ordered the intelligence community to redouble efforts to analyze the evidence. While that work was going on, the leaks kept coming. In a 12,000-word story for Vanity Fair, the investigative journalist Katherine Eban gave some backstory on the sick-research intelligence, claiming that it had been gathered in 2020 and then inexplicably file-drawered until State Department investigators rediscovered it. (One former senior official described this as a “holy shit” moment in an interview with Eban.) Her article contained another seemingly important detail, too: The sickened researchers were doing not simply coronavirus research, her sources told her, but the very sort of research that could produce amped-up versions of a pathogen—an approach known as “gain of function.” Later in the summer, Josh Rogin, a Washington Post columnist, added that, according to his unnamed sources, the sickened researchers had lost their sense of smell and developed ground-glass opacities in their lungs. By this point, in the middle of 2021, the expanded piece of intel amounted to the following:

    Three gain-of-function coronavirus researchers at WIV became severely ill with COVID-like symptoms in the second week of November 2019 and sought hospital care.

    The latest revelations are coming at just the moment when Republicans are lambasting the Biden administration for failing to declassify COVID-origins intelligence in accordance with a law that the president signed. The Sunday Times quoted an anonymous former State Department investigator who said they were “rock-solid confident” that the three sick researchers had been sick with COVID, because people as young as the researchers would rarely be hit so hard by a mere seasonal illness. A few days later, someone spilled the researchers’ names to Public. On Tuesday, The Wall Street Journal matched the scoop, and it seemed that every detail of the once-secret information was now exposed:

    Ben Hu, Yu Ping, and Yan Zhu, three gain-of-function coronavirus researchers at WIV, became severely ill with COVID-like symptoms in the second week of November 2019 and sought hospital care.

    However vivid this may sound, its credibility remains unknown. Did Hu, Ping, and Zhu really get sick, as the intel claims? If so, was it really COVID? Two years ago, the Journal cited two anonymous sources on this question: One, the Journal wrote, called the intelligence “potentially significant but still in need of further investigation and corroboration”; the other said it was “of exquisite quality” and “very precise.” Just this week, anonymous officials in the Biden administration told The New York Times that intelligence analysts had already “dismissed the evidence,” by August 2022, about the sickened workers at WIV for lack of relevance. Which secret source should be trusted to explain the significance of this secret intelligence? Readers are left to sort that out themselves.

    Read: Don’t fall for these lab-leak traps

    In the meantime, over the past two years, even as the sickened-worker intel was revealed, a very different sort of evidence was mounting, too. A new research paper, published just days after Eban’s feature in Vanity Fair, revealed that live wild animals, including raccoon dogs, had been for sale at the Huanan market in Wuhan shortly before the pandemic started. In early 2022, scientists put out two detailed analyses of early case patterns and viral genome data, which argued in favor of the animal-spillover theory. Another study involving many of the same researchers came out this past spring, noting the presence of genetic material from raccoon dogs in early samples from the market; its authors described their findings as providing strong evidence for an animal origin. But other scientists were quick to challenge the study’s importance. A further study of the same data by Chinese scientists made a point of not ruling out the hypothesis that the pandemic had started with a case of tainted frozen seafood; yet another study, released in May, argued that the original work provided no useful information whatsoever on the question of COVID’s origins.

    So it goes with the animal-spillover theory. The evidence in favor has always been highly esoteric, knotted with data and interpretation. Scientific points are made—a particular run of viral nucleotides is a “smoking gun” for genetic engineering, one famous scholar said in 2021—and then they are re-argued and occasionally walked back. Long-hidden sample data from the market suddenly appear, and their meaning is subjected to vituperative, technical debate. If the evidence for a lab leak tends to come from messy human stuff, the evidence for animal spillover emerges from messy data. Simple-seeming claims are draped across a sprawl of numbers.

    In this way, the origins question has broken down into a pair of rival theories that don’t—and can’t—ever fully interact. They’re based on different sorts of evidence, with different standards for evaluation and debate. Each story may be accruing new details—fresh intelligence about the goings-on at WIV, for example, or fresh genomic data from the market—but these are only filling out a picture that will never be complete. The two narratives have been moving forward on different tracks. Neither one is getting to its destination.

    Daniel Engber

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  • Only the Emergency Has Ended

    Only the Emergency Has Ended

    Emergency responses—being, well, emergency responses—aren’t designed to last forever, and this morning, the World Health Organization declared the one that’s been in place for the COVID-19 pandemic since January 2020 officially done. “This virus is here to stay. It is still killing, and it’s still changing,” Tedros Adhanom Ghebreyesus, the director general of the WHO, said at a press conference; although the coronavirus will continue to pose a threat, the time had simply come, he and his colleagues said, for countries to move away from treating it as a global crisis.

    And, really, they already have: The United States, for instance, ended its national emergency last month and will sunset its public-health emergency next week; countries around the world have long since shelved testing programs, lifted lockdowns, dispensed with masking mandates, and even stopped recommending frequent COVID shots to healthy people in certain age groups. In some ways, the WHO was already a straggler. Had it waited much longer, the power of its designation of COVID as a “public health emergency of international concern,” or PHEIC, “would have been undermined,” says Salim Abdool Karim, the director of the Centre for the AIDS Program of Research in South Africa.

    There’s no disputing that the virus’s threat has ebbed since the pandemic’s worst days. By and large, “we are in our recovery phase now”—not perfectly stabilized, but no longer in chaotic flux, says René Najera, the director of public health at the College of Physicians of Philadelphia. Still, ending the emergency doesn’t mean that the world has fully addressed the problems that made this an emergency. Global vaccine distribution remains wildly inequitable, leaving many people susceptible to the virus’s worst effects; deaths are still concentrated among those most vulnerable; the virus’s evolutionary and transmission patterns are far from predictable or seasonal. Now, ending the emergency is less an epidemiological decision than a political one: Our tolerance for these dangers has grown to the extent that most people are doing their best to look away from the remaining risk, and will continue to until the virus forces us to turn back.

    The end to the PHEIC, to be clear, isn’t a declaration that COVID is over—or even that the pandemic is. Both a PHEIC and a pandemic tend to involve the rapid and international spread of a dangerous disease, and the two typically do go hand in hand. But no set-in-stone rules delineate when either starts or ends. Plenty of diseases have met pandemic criteria—noted by many epidemiologists as an epidemic that’s rapidly spread to several continents—without ever being granted a PHEIC, as is the case with HIV. And several PHEICs, including two of the Ebola outbreaks of the past decade and the Zika epidemic that began in 2015, did not consistently earn the pan- prefix among experts. With COVID, the WHO called a PHEIC more than a month before it publicly labeled the outbreak a pandemic on March 11. Now the organization has bookended its declaration with a similar mismatch: one crisis designation on and the other off. That once again leaves the world in a bizarre risk limbo, with the threat everywhere but our concern for it on the wane.

    For other diseases with pandemic potential, understanding the start and end of crisis has been simpler. After a new strain of H1N1 influenza sparked a global outbreak in 2009, disrupting the disease’s normal seasonal ebb and flow, scientists simply waited until the virus’s annual transmission patterns went back to their pre-outbreak baseline, then declared that particular pandemic done. But “we don’t really have a baseline” to return to for SARS-CoV-2, says Sam Scarpino, an infectious-disease modeler at Northeastern University. This has left officials floundering for an end-of-pandemic threshold to meet. Once, envisioning that coda seemed more possible: In February 2021, when the COVID shots were still new, Alexis Madrigal wrote in The Atlantic that, in the U.S. at least, pandemic restrictions might end once the country reached some relatively high rate of vaccination, or drove daily deaths below 100—approximating the low-ish end of the flu’s annual toll.

    Those criteria aren’t perfect. Given how the virus has evolved, even, say, an 85 percent vaccination rate probably wouldn’t have squelched the virus in a way public-health experts were envisioning in 2021 (and wouldn’t have absolved us of booster maintenance). And even if the death toll slipped below 100 deaths a day, the virus’s chronic effects would still pose an immense threat. But thresholds such as those, flawed though they were, were never even set. “I’m not sure we ever set any goals at all” to designate when we’d have the virus beat, Céline Gounder, an infectious-disease physician at NYU and an editor-at-large for public health at KFF Health News, told me. And if they had been, we probably still would not have met them: Two years out, we certainly have not.

    Instead, efforts to mitigate the virus have only gotten laxer. Most individuals are no longer masking, testing, or staying up to date on their shots; on community scales, the public goods that once seemed essential—ventilation, sick leave, equitable access to insurance and health care—have already faded from most discourse. That COVID has been more muted in recent months feels “more like luck” than a product of concerted muffling from us, Scarpino told me. Should another SARS-CoV-2 variant sweep the world or develop resistance to Paxlovid, “we don’t have much in the way of a plan,” he said.

    If and when the virus troubles us again, our lack of preparedness will be a reflection of America’s classically reactive approach to public health. Even amid a years-long emergency declaration that spanned national and international scales, we squandered the opportunity “to make the system more resilient to the next crisis,” Gounder said. There is little foresight for what might come next. And individuals are still largely being asked to fend for themselves—which means that as this emergency declaration ends, we are setting ourselves up for another to inevitably come, and hit us just as hard.

    As the final roadblocks to declaring normalcy disappear, we’re unlikely to patch those gaps. The PHEIC, at this point, was more symbolic than practical—but that didn’t make it inconsequential. Experts worry that its end will sap what remaining incentive there was for some countries to sustain a COVID-focused response—one that would, say, keep vaccines, treatments, and tests in the hands of those who need them most. “Public interest is very binary—it’s either an emergency or it’s not,” says Saskia Popescu, an infection-prevention expert at George Mason University. With the PHEIC now gone, the world has officially toggled itself to “not.” But there’s no going back to 2019. Between that and the height of the pandemic is middle-ground maintenance, a level of concern and response that the world has still not managed to properly calibrate.

    Katherine J. Wu

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  • Will COVID’s Spring Lull Last?

    Will COVID’s Spring Lull Last?

    By all official counts—at least, the ones still being tallied—the global situation on COVID appears to have essentially flatlined. More than a year has passed since the world last saw daily confirmed deaths tick above 10,000; nearly a year and a half has elapsed since the population was pummeled by a new Greek-lettered variant of concern. The globe’s most recent winters have been the pandemic’s least lethal to date—and the World Health Organization is mulling lifting its COVID emergency declaration sometime later this year, as the final pandemic protections in the United States prepare to disappear. On the heels of the least-terrible winter since the pandemic’s onset, this spring in the U.S. is also going … kind of all right. “I am feeling less worried than I have been in a while,” Shweta Bansal, an infectious-disease modeler at Georgetown University, told me.

    That sense of phew, though, Bansal said, feels tenuous. The coronavirus’s evolution is not yet predictable; its effects are nowhere near benign. This might be the longest stretch of quasi-normalcy that humanity has had since 2020’s start, but experts can’t yet tell whether we’re at the beginning of post-pandemic stability or in the middle of a temporary reprieve. For now, we’re in a holding pattern, a sort of extended coda or denouement. Which means that our lived experience and scientific reality might not match up for a good while yet.

    Read: The next stage of COVID is starting now

    There is, to be fair, reason to suspect that some current trends will stick. The gargantuan waves of seasons past were the rough product of three factors: low population immunity, genetic changes that allowed SARS-CoV-2 to skirt what immunity did exist, and upswings in behaviors that brought people and the virus into frequent contact. Now, though, just about everyone has had some exposure to SARS-CoV-2’s spike protein, whether by infection or injection. And most Americans have long since dispensed with masking and distancing, maintaining their exposure at a consistently high plateau. That leaves the virus’s shape-shifting as the only major wild card, says Emily Martin, an infectious-disease epidemiologist at the University of Michigan. SARS-CoV-2 could, for instance, make another evolutionary leap large enough to re-create the Omicron wave of early 2022—but a long time has passed since the virus managed such a feat. Tentatively, carefully, experts are hopeful that we’re at last in a “period that could be kind of indicative of what the new normal really is,” says Virginia Pitzer, an infectious-disease epidemiologist at Yale.

    Top American officials are already gambling on that guess. At a conference convened in late March by the Massachusetts Medical Society, Ashish Jha, the outgoing coordinator of the White House COVID-19 Response Team, noted that the relative tameness of this past winter was a major deciding factor in the Biden administration’s decision to let the U.S. public-health emergency lapse. The crisis-caliber measures that were essential at the height of the pandemic, Jha said, were no longer “critical at this moment” to keep the nation’s health-care system afloat. Americans could rely instead primarily on shots and antivirals to keep themselves healthy—“If you are up to date on your vaccines and you get treated with Paxlovid, if you get an infection, you just don’t die of this virus,” he said. (That math, of course, doesn’t hold up as well for certain vulnerable groups, including the elderly and the immunocompromised.) The pharmaceuticals-only strategy asks much less of people: Going forward, most Americans will need to dose up on their COVID vaccines only once a year in the fall, a la seasonal flu shots.

    Making sweeping assessments at this particular juncture, though, is tough. Experts expect SARS-CoV-2 cases to take a downturn as winter transitions into spring—as many other respiratory viruses do. And a half-ish year of relative quietude is, well, just a half-ish year of relative quietude—too little data for scientists to definitively declare the virus seasonal, or even necessarily stable in its annual patterns. One of the most telling intervals is yet to come: the Northern Hemisphere’s summer, says Alyssa Bilinski, a health-policy researcher at Brown University. In previous years, waves of cases have erupted pretty consistently during the warmer months, especially in the American South, as people flock indoors to beat the heat.

    SARS-CoV-2 might not end up being recognizably seasonal at all. So far, the virus has circulated more or less year-round, with erratic bumps in the winter and, to a lesser extent, the summer. “There is a consistency there that is very enticing,” Bansal told me. But many of the worst surges we’ve weathered were driven by a lack of immunity, which is less of an issue now. “So I like to be extremely careful about the seasonality argument,” she said. In future years, the virus may break from its summer-winter shuffle. How SARS-CoV-2 will continue to interact with other respiratory viruses, such as RSV and flu, also remains to be seen. After an extended hiatus, driven largely by pandemic mitigations, those pathogens came roaring back this past autumn—making it more difficult, perhaps, for the coronavirus to find unoccupied hosts. Experts can’t yet tell whether future winters will favor the coronavirus or its competitors. Either way, scientists won’t know until they’ve collected several more years of evidence—“I would want at least a handful, like four or five,” Bansal said.

    Amassing those numbers is only getting tougher, though, as data streams dry up, Martin told me. Virus-surveillance systems are being dismantled; soon, hospitals and laboratories will no longer be required to share their COVID data with federal officials. Even independent trackers have sunsetted their regular updates. Especially abysmal are estimates of total infections, now that so many people are using only at-home tests, if they’re testing at all—and metrics such as hospitalization and death don’t fully reflect where and when the virus is moving, and which new variants may be on the rise.

    Shifts in long-term approaches to virus control could also upend this period of calm. As tests, treatments, and vaccines become privatized, as people lose Medicaid coverage, as community-outreach programs fight to stay afloat, the virus will find the country’s vulnerable pockets again. Those issues aren’t just about the coming months: COVID-vaccination rates among children remain worryingly low—a trend that could affect the virus’s transmission patterns for decades. And should the uptake of annual COVID shots continue on its current trajectory—worse, even, than America’s less-than-optimal flu vaccination rates—or dip even further down, rates of severe disease may begin another upward climb. Experts also remain concerned about the ambiguities around long COVID, whose risks remain ill-defined.

    Read: Long COVID is being erased—again

    We could get lucky. Maybe 2023 is the start of a bona fide post-pandemic era; maybe the past few months are genuinely offering a teaser trailer of decades to come. But even if that’s the case, it’s not a full comfort. COVID remains a leading cause of death in the United States, where the virus continues to kill about 200 to 250 people each day, many of them among the population’s most vulnerable and disenfranchised. It’s true that things are better than they were a couple of years ago. But in some ways, that’s a deeply unfair comparison to make. Deaths would have been higher when immunity was low; vaccines, tests, and treatments were scarce; and the virus was far less understood. “I would hope our standard for saying that we’ve succeeded and that we don’t need to do more is not Are we doing better than some of the highest-mortality years in history?” Bilinski told me. Perhaps the better question is why we’re settling for the status quo—a period of possible stability that may be less a relief and more a burden we’ve permanently stuck ourselves with.

    Katherine J. Wu

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  • A Major Clue to COVID’s Origins Is Just Out of Reach

    A Major Clue to COVID’s Origins Is Just Out of Reach

    Updated at 2:45 p.m. on March 21, 2023

    Last week, the ongoing debate about COVID-19’s origins acquired a new plot twist. A French evolutionary biologist stumbled across a trove of genetic sequences extracted from swabs collected from surfaces at a wet market in Wuhan, China, shortly after the pandemic began; she and an international team of colleagues downloaded the data in hopes of understanding who—or what—might have ferried the virus into the venue. What they found, as The Atlantic first reported on Thursday, bolsters the case for the pandemic having purely natural roots: The genetic data suggest that live mammals illegally for sale at the Huanan Seafood Wholesale Market—among them, raccoon dogs, a foxlike species known to be susceptible to the virus—may have been carrying the coronavirus at the end of 2019.

    But what might otherwise have been a straightforward story on new evidence has rapidly morphed into a mystery centered on the origins debate’s data gaps. Within a day or so of nabbing the sequences off a database called GISAID, the researchers told me, they reached out to the Chinese scientists who had uploaded the data to share some preliminary results. The next day, public access to the sequences was locked—according to GISAID, at the request of the Chinese researchers, who had previously analyzed the data and drawn distinctly different conclusions about what they contained.

    Read: The strongest evidence yet that an animal started the pandemic

    Yesterday evening, the international team behind the new Huanan-market analysis released a report on its findings—but did not post the underlying data. The write-up confirms that genetic material from raccoon dogs and several other mammals was found in some of the same spots at the wet market, as were bits of SARS-CoV-2’s genome around the time the outbreak began. Some of that animal genetic material, which was collected just days or weeks after the market was shut down, appears to be RNA—a particularly fast-degrading molecule. That strongly suggests that the mammals were present at the market not long before the samples were collected, making them a plausible channel for the virus to travel on its way to us. “I think we’re moving toward more and more evidence that this was an animal spillover at the market,” says Ravindra Gupta, a virologist at the University of Cambridge, who was not involved in the new research. “A year and a half ago, my confidence in the animal origin was 80 percent, something like that. Now it’s 95 percent or above.”

    For now, the report is just that: a report, not yet formally reviewed by other scientists or even submitted for publication to the journal—and that will remain the case as long as this team continues to leave space for the researchers who originally collected the market samples, many of them based at the Chinese Center for Disease Control and Prevention, to prepare a paper of their own. And still missing are the raw sequence files that sparked the reanalysis in the first place—before vanishing from the public eye.

    Every researcher I asked emphasized just how important the release of that evidence is to the origins investigation: Without data, there’s no base-level proof—nothing for the broader scientific community to independently scrutinize to confirm or refute the international team’s results. Absent raw data, “some people will say that this isn’t real,” says Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security, who wasn’t involved in the new analysis. Data that flicker on and off publicly accessible parts of the internet also raise questions about other clues on the pandemic’s origins. Still more evidence might be out there, yet undisclosed.

    Transparency is always an essential facet of research, but all the more so when the stakes are so high. SARS-CoV-2 has already killed nearly 7 million people, at least, and saddled countless people with chronic illness; it will kill and debilitate many more in the decades to come. Every investigation into how it began to spread among humans must be “conducted as openly as possible,” says Sarah Cobey, an infectious-disease modeler at the University of Chicago, who wasn’t involved in the new analysis.

    The team behind the reanalysis still has copies of the genetic sequences its members downloaded earlier this month. But they’ve decided that they won’t be the ones to share them, several of them told me. For one, they don’t have sequences from the complete set of samples that the Chinese team collected in early 2020—just the fraction that they spotted and grabbed off GISAID. Even if they did have all of the data, the researchers contend that it’s not their place to post them publicly. That’s up to the China CDC team that originally collected and generated the data.

    Part of the international team’s reasoning is rooted in academic decorum. There isn’t a set-in-stone guidebook among scientists, but adhering to unofficial rules on etiquette smooths successful collaborations across disciplines and international borders—especially during a global crisis such as this one. Releasing someone else’s data, the product of another team’s hard work, is a faux pas. It risks misattribution of credit, and opens the door to the Chinese researchers’ findings getting scooped before they publish a high-profile paper in a prestigious journal. “It isn’t right to share the original authors’ data without their consent,” says Niema Moshiri, a computational biologist at UC San Diego and one of the authors of the new report. “They produced the data, so it’s their data to share with the world.”

    If the international team released what data it has, it could potentially stoke the fracas in other ways. The World Health Organization has publicly indicated that the data should come from the researchers who collected them first: On Friday, at a press briefing, Tedros Adhanom Ghebreyesus, the WHO’s director-general, admonished the Chinese researchers for keeping their data under wraps for so long, and called on them to release the sequences again. “These data could have and should have been shared three years ago,” he said. And the fact that it wasn’t is “disturbing,” given just how much it might have aided investigations early on, says Gregory Koblentz, a biodefense expert at George Mason University, who wasn’t involved in the new analysis.

    Publishing the current report has already gotten the researchers into trouble with GISAID, the database where they found the genetic sequences. During the pandemic, the database has been a crucial hub for researchers sharing viral genome data; founded to provide open access to avian influenza genomes, it is also where researchers from the China CDC published the first whole-genome sequences of SARS-CoV-2, back in January 2020. A few days after the researchers downloaded the sequences, they told me, several of them were contacted by a GISAID administrator who chastised them about not being sufficiently collaborative with the China CDC team and warned them against publishing a paper using the China CDC data. They were in danger, the email said, of violating the site’s terms of use and would risk getting their database access revoked. Distributing the data to any non-GISAID users—including the broader research community—would also be a breach.

    This morning, hours after the researchers released their report online, many of them found that they could no longer log in to GISAID—they received an error message when they input their username and password. “They may indeed be accusing us of having violated their terms,” Moshiri told me, though he can’t be sure. The ban was instated with absolutely no warning. Moshiri and his colleagues maintain that they did act in good faith and haven’t violated any of the database’s terms—that, contrary to GISAID’s accusations, they reached out multiple times with offers to collaborate with the China CDC, which has “thus far declined,” per the international team’s report.

    GISAID didn’t respond when I reached out about the data’s disappearing act, its emails to the international team, and the group-wide ban. But in a statement released shortly after I contacted the database—one that echoes language in the emails sent to researchers—GISAID doubled down on accusing the international team of violating its terms of use by posting “an analysis report in direct contravention of the terms they agreed to as a condition to accessing the data, and despite having knowledge that the data generators are undergoing peer review assessment of their own publication.”

    Maria Van Kerkhove, the WHO’s COVID-19 technical lead, told me that she’s learned that the China CDC researchers recently provided a fuller data set to GISAID—more complete than the one the international team downloaded earlier this month. “It’s ready to go,” she told me. GISAID just needs permission, she said, from the Chinese researchers to make the sequences publicly available. “I reach out to them every day, asking them for a status update,” she added, but she hasn’t yet heard back on a definitive timeline. In its statement, GISAID also “strongly” suggested “that the complete and updated dataset will be made available as soon as possible,” but gave no timeline. I asked Van Kerkhove if there was a hypothetical deadline for the China CDC team to restore access, at which point the international team might be asked to publicize the data instead. “This hypothetical deadline you’re talking about? We’re way past that,” she said, though she didn’t comment specifically on whether the international team would be asked to step in. “Data has been uploaded. It is available. It just needs to be accessible, immediately.”

    Why, exactly, the sequences were first made public only so recently, and why they have yet to reappear publicly, remain unclear. In a recent statement, the WHO said that access to the data was withdrawn “apparently to allow further data updates by China CDC” to its original analysis on the market samples, which went under review for publication at the journal Nature last week. There’s no clarity, however, on what will happen if the paper is not published at all. When I reached out to three of the Chinese researchers—George Gao, William Liu, and Guizhen Wu—to ask about their intentions for the data, I didn’t receive a response.

    “We want the data to come out more than anybody,” says Saskia Popescu, an infectious-disease epidemiologist at George Mason University and one of the authors on the new analysis. Until then, the international team will be fielding accusations, already flooding in, that it falsified its analyses and overstated its conclusions.

    Researchers around the world have been raising questions about these particular genetic sequences for at least a year. In February 2022, the Chinese researchers and their close collaborators released their analysis of the same market samples probed in the new report, as well as other bits of genetic data that haven’t yet been made public. But their interpretations deviate pretty drastically from the international team’s. The Chinese team contended that any shreds of virus found at the market had most likely been brought in by infected humans. “No animal host of SARS-CoV-2 can be deduced,” the researchers asserted at the time. Although the market had perhaps been an “amplifier” of the outbreak, their analysis read, “more work involving international coordination” would be needed to determine the “real origins of SARS-CoV-2.” When reached by Jon Cohen of Science magazine last week, Gao described the sequences that fleetingly appeared on GISAID as “[n]othing new. It had been known there was illegal animal dealing and this is why the market was immediately shut down.”

    There is, then, a clear divergence between the two reports. Gao’s assessment indicates that finding animal genetic material in the market swabs merely confirms that live mammals were being illegally traded at the venue prior to January 2020. The researchers behind the new report insist that the narrative can now go a step further—they suggest not just that the animals were there, but that the animals, several of which are already known to be vulnerable to SARS-CoV-2, were there, in parts of the market where the virus was also found. That proximity, coupled with the virus’s inability to persist without a viable host, points to the possibility of an existing infection among animals, which could spark several more.

    The Chinese researchers used this same logic of location—multiple types of genetic material pulled out of the same swab—to conclude that humans were carrying around the virus at Huanan. The reanalysis confirms that there probably were infected people at the market at some point before it closed. But they were unlikely to be the virus’s only chauffeurs: Across several samples, the amount of raccoon-dog genetic material dwarfs that of humans. At one stall in particular—located in the sector of the market where the most virus-positive swabs were found—the researchers discovered at least one sample that contained SARS-CoV-2 RNA, and was also overflowing with raccoon-dog genetic material, while containing very little DNA or RNA material matching the human genome. That same stall was photographically documented housing raccoon dogs in 2014. The case is not a slam dunk: No one has yet, for instance, identified a viral sample taken from a live animal that was swabbed at the market in 2019 before the venue was closed. Still, JHU’s Gronvall told me, the situation feels clearer than ever. “All of the science is pointed” in the direction of Huanan being the pandemic’s epicenter, she said.

    To further untangle the significance of the sequences will require—you guessed it—the now-vanished genetic data. Some researchers are still withholding their judgment on the significance of the new analysis, because they haven’t gotten their hands on the genetic sequences themselves. “That’s the whole scientific process,” Van Kerkhove told me: data transparency that allows analyses to be “done and redone.”

    Van Kerkhove and others are also wondering whether more data could yet emerge, given how long this particular set went unshared. “This is an indication to me in recent days that there is more data that exists,” she said. Which means that she and her colleagues haven’t yet gotten the fullest picture of the pandemic’s early days that they could—and that they won’t be able to deliver much of a verdict until more information emerges. The new analysis does bolster the case for market animals acting as a conduit for the virus between bats (SARS-CoV-2’s likeliest original host, based on several studies on this coronavirus and others) and people; it doesn’t, however, “tell us that the other hypotheses didn’t happen. We can’t remove any of them,” Van Kerkhove told me.

    More surveillance for the virus needs to be done in wild-animal populations, she said. Having the data from the market swabs could help with that, perhaps leading back to a population of mammals that might have caught the virus from bats or another intermediary in a particular part of China. At the same time, to further investigate the idea that SARS-CoV-2 first emerged out of a laboratory mishap, officials need to conduct intensive audits and investigations of virology laboratories in Wuhan and elsewhere. Last month, the U.S. Department of Energy ruled that such an accident was the likelier catalyst of the coronavirus outbreak than a natural spillover from wild animals to humans. The ruling echoed earlier judgments from the FBI and a Senate minority report. But it contrasted with the views of four other agencies, plus the National Intelligence Council, and it was made with “low confidence” and based on “new” evidence that has yet to be declassified.

    Read: The lab leak will haunt us forever

    The longer the investigation into the virus’s origins drags on, and the more distant the autumn of 2019 grows in our rearview, “the harder it becomes,” Van Kerkhove told me. Many in the research community were surprised that new information from market samples collected in early 2020 emerged at all, three years later. Settling the squabbles over SARS-CoV-2 will be especially tough because the Huanan market was so swiftly shut down after the outbreak began, and the traded animals at the venue rapidly culled, says Angela Rasmussen, a virologist at the University of Saskatchewan and one of the researchers behind the new analysis. Raccoon dogs, one of the most prominent potential hosts to have emerged from the new analysis, are not even known to have been sampled live at the market. “That evidence is gone now,” if it ever existed, Koblentz, of George Mason University, told me. For months, Chinese officials were even adamant that no mammals were being illegally sold at the region’s wet markets at all.

    So researchers continue to work with what they have: swabs from surfaces that can, at the very least, point to a susceptible animal being in the right place, at the right time, with the virus potentially inside it. “Right now, to the best of my knowledge, this data is the only way that we can actually look,” Rasmussen told me. It may never be enough to fully settle this debate. But right now, the world doesn’t even know the extent of the evidence available—or what could, or should, still emerge.

    Katherine J. Wu

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  • The Strongest Evidence Yet That an Animal Started the Pandemic

    The Strongest Evidence Yet That an Animal Started the Pandemic

    For three years now, the debate over the origins of the coronavirus pandemic has ping-ponged between two big ideas: that SARS-CoV-2 spilled into human populations directly from a wild-animal source, and that the pathogen leaked from a lab. Through a swirl of data obfuscation by Chinese authorities and politicalization within the United States, and rampant speculation from all corners of the world, many scientists have stood by the notion that this outbreak—like most others—had purely natural roots. But that hypothesis has been missing a key piece of proof: genetic evidence from the Huanan Seafood Wholesale Market in Wuhan, China, showing that the virus had infected creatures for sale there.

    This week, an international team of virologists, genomicists, and evolutionary biologists may have finally found crucial data to help fill that knowledge gap. A new analysis of genetic sequences collected from the market shows that raccoon dogs being illegally sold at the venue could have been carrying and possibly shedding the virus at the end of 2019. It’s some of the strongest support yet, experts told me, that the pandemic began when SARS-CoV-2 hopped from animals into humans, rather than in an accident among scientists experimenting with viruses.

    “This really strengthens the case for a natural origin,” says Seema Lakdawala, a virologist at Emory who wasn’t involved in the research. Angela Rasmussen, a virologist involved in the research, told me, “This is a really strong indication that animals at the market were infected. There’s really no other explanation that makes any sense.”

    The findings won’t fully silence the entrenched voices on either side of the origins debate. But the new analysis may offer some of the clearest and most compelling evidence that the world will ever get in support of an animal origin for the virus that, in just over three years, has killed nearly 7 million people worldwide.

    Read: The lab leak will haunt us forever

    The genetic sequences were pulled out of swabs taken in and near market stalls around the pandemic’s start. They represent the first bits of raw data that researchers outside of China’s academic institutions and their direct collaborators have had access to. Late last week, the data were quietly posted by researchers affiliated with the country’s Center for Disease Control and Prevention, on an open-access genomic database called GISAID. By almost pure happenstance, scientists in Europe, North America, and Australia spotted the sequences, downloaded them, and began an analysis.

    The samples were already known to be positive for the coronavirus, and had been scrutinized before by the same group of Chinese researchers who uploaded the data to GISAID. But that prior analysis, released as a preprint publication in February 2022, asserted that “no animal host of SARS-CoV-2 can be deduced.” Any motes of coronavirus at the market, the study suggested, had most likely been chauffeured in by infected humans, rather than wild creatures for sale.

    The new analysis, led by Kristian Andersen, Edward Holmes, and Michael Worobey—three prominent researchers who have been looking into the virus’s roots—shows that that may not be the case. Within about half a day of downloading the data from GISAID, the trio and their collaborators discovered that several market samples that tested positive for SARS-CoV-2 were also coming back chock-full of animal genetic material—much of which was a match for the common raccoon dog. Because of how the samples were gathered, and because viruses can’t persist by themselves in the environment, the scientists think that their findings could indicate the presence of a coronavirus-infected raccoon dog in the spots where the swabs were taken. Unlike many of the other points of discussion that have been volleyed about in the origins debate, the genetic data are “tangible,” Alex Crits-Christoph, a computational biologist and one of the scientists who worked on the new analysis, told me. “And this is the species that everyone has been talking about.”

    Finding the genetic material of virus and mammal so closely co-mingled—enough to be extracted out of a single swab—isn’t perfect proof, Lakdawala told me. “It’s an important step, I’m not going to diminish that,” she said. Still, the evidence falls short of, say, isolating SARS-CoV-2 from a free-ranging raccoon dog or, even better, uncovering a viral sample swabbed from a mammal for sale at Huanan from the time of the outbreak’s onset. That would be the virological equivalent of catching a culprit red-handed. But “you can never go back in time and capture those animals,” says Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security. And to researchers’ knowledge, “raccoon dogs were not tested at the market and had likely been removed prior to the authorities coming in,” Andersen wrote to me in an email. He underscored that the findings, while an important addition, are still not “direct evidence of infected raccoon dogs at the market.”

    Still, the findings don’t stand alone. “Do I believe there were infected animals at the market? Yes, I do,” Andersen told me. “Does this new data add to that evidence base? Yes.” The new analysis builds on extensive previous research that points to the market as the source of the earliest major outbreak of SARS-CoV-2: Many of the earliest known COVID-19 cases of the pandemic were clustered roughly in the market’s vicinity. And the virus’s genetic material was found in many samples swabbed from carts and animal processing equipment at the venue, as well as parts of nearby infrastructure, such as storehouses, sewage wells, and water drains. Raccoon dogs, creatures commonly bred for sale in China, are also already known to be one of many mammal species that can easily catch and spread the coronavirus. All of this left one main hole in the puzzle to fill: clear-cut evidence that raccoon dogs and the virus were in the exact same spot at the market, close enough that the creatures might have been infected and, possibly, infectious. That’s what the new analysis provides. Think of it as finding the DNA of an investigation’s main suspect at the scene of the crime.

    The findings don’t rule out the possibility that other animals may have been carrying SARS-CoV-2 at Huanan. Raccoon dogs, if they were infected, may not even be the creatures who passed the pathogen on to us. Which means the search for the virus’s many wild hosts will need to plod on. “Do we know the intermediate host was raccoon dogs? No,” Andersen wrote to me, using the term for an animal that can ferry a pathogen between other species. “Is it high up on my list of potential hosts? Yes, but it’s definitely not the only one.”

    On Tuesday, the researchers presented their findings at a hastily scheduled meeting of the World Health Organization’s Scientific Advisory Group for the Origins of Novel Pathogens, which was also attended by several of the Chinese researchers responsible for the original analysis, according to multiple researchers who were not present but were briefed about it before and after by multiple people who were there.

    Shortly after the meeting, the Chinese team’s preprint went into review at a Nature Research journal—suggesting that a new version was being prepared for publication. (I reached out to the WHO for comment and will update the story when I have more information.)

    At this point, it’s still unclear why the sequences were posted to GISAID last week. They also vanished from the database shortly after appearing, without explanation. When I emailed George Gao, the former China CDC director-general and the lead author on the original Chinese analysis, asking for his team’s rationale, I didn’t immediately receive a response. Given what was in the GISAID data, it does seem that raccoon dogs could have been introduced into and clarified the origins narrative far sooner—at least a year ago, and likely more.

    China has, for years, been keen on pushing the narrative that the pandemic didn’t start within its borders. In early 2020, a Chinese official suggested that the novel coronavirus may have emerged from a U.S. Army lab in Maryland. The notion that a dangerous virus sprang out from wet-market mammals echoed the beginnings of the SARS-CoV-1 epidemic two decades ago—and this time, officials immediately shut down the Huanan market, and vehemently pushed back against assertions that live animals being sold illegally in the the country were to blame; a WHO investigation in March 2021 took the same line. “No verified reports of live mammals being sold around 2019 were found,” the report stated. But just three months later, in June 2021, a team of researchers published a study documenting tens of thousands of mammals for sale in wet markets in Wuhan between 2017 and late 2019, including at Huanan. The animals were kept in largely illegal, cramped, and unhygienic settings—conditions conducive to viral transmission—and among them were more than 1,000 raccoon dogs. Holmes himself had been at the market in 2014 and snapped a photo at Stall 29, clearly showing a raccoon dog in a cage; another set of images from the venue, captured by a local in December 2019 and later shared on Weibo, caught the animals on film as well—right around the time that the first recorded SARS-CoV-2 infections in humans occurred.

    And yet, Chinese researchers maintained their stance. As Jon Cohen reported for Science magazine last year, scientists from several of China’s largest academic institutions posted a preprint in September 2021 concluding that a massive nationwide survey of bats—the likeliest original source of the coronavirus before it jumped into an intermediate host, such as raccoon dogs, and then into us—had turned up no relatives of SARS-CoV-2. The implication, the team behind the paper asserted, was that relatives of the coronavirus were “extremely rare” in the region, making it unlikely that the pandemic had started there. The findings directly contradicted others showing that cousins of SARS-CoV-2 were indeed circulating in China’s bats. (Local bats have also been found to harbor viruses related to SARS-CoV-1.)

    The original Chinese analysis of the Huanan market swabs, from February 2022, also stuck with China’s party line on the pandemic. One of the report’s graphs suggested that viral material at the market had been mixed up with genetic material of multiple animal species—a data trail that should have led to further inquiry or conclusions, but which the Chinese researchers appear to have ignored. Their report noted only humans as being linked to SARS-CoV-2, stating that its findings “highly” suggested that any viral material at the market came from people (at least one of whom, presumably, picked it up elsewhere and ferried it into the venue). The Huanan market, the study’s authors wrote, “might have acted as an amplifier” for the epidemic. But “more work involving international coordination” would be needed to suss out the “real origins of SARS-CoV-2.”

    The wording of that report baffled many scientists in Europe, North America, and Australia, several of whom had, almost exactly 24 hours after the release of the China CDC preprint, published early versions of their own studies, concluding that the Huanan market was the pandemic’s probable epicenter—and that SARS-CoV-2 might have made its hop into humans from the venue twice at the end of 2019. Itching to get their hands on China CDC’s raw data, some of the researchers took to regularly trawling GISAID, occasionally at odd hours—the only reason that Florence Débarre, an evolutionary biologist at the French National Centre for Scientific Research, spotted the sequences pinging onto the server late last Thursday night with no warning or fanfare.

    Within hours of downloading the data and starting their own analysis, the researchers found their suspicions confirmed. Several surfaces in and around one stall at the market, including a cart and a defeathering machine, produced virus-positive samples that also contained genetic material from raccoon dogs—in a couple of cases, at higher concentrations than of human genomes. It was Stall 29—the same spot where Holmes had snapped the photo of the raccoon dog, nearly a decade before.

    Slam-dunk evidence for a raccoon-dog host—or another animal—could still emerge. In the hunt for the wild source of MERS, another coronavirus that caused a deadly outbreak in 2012, researchers were eventually able to identify the pathogen in camels, which are thought to have caught their initial infection from bats—and which still harbor the virus today; a similar story has played out for Nipah virus, which hopscotched from bats to pigs to us.

    Read: Bird flu leaves the world with an existential choice

    Proof of that caliber, though, may never turn up for SARS-CoV-2. (Nailing wild origins is rarely simple: Despite a years-long search, the wild host for Ebola still has not been definitively pinpointed.) Which leaves just enough ambiguity to keep debate about the pandemic’s origins running, potentially indefinitely. Skeptics will likely be eager to poke holes in the team’s new findings—pointing out, for instance, that it’s technically possible for genetic material from viruses and animals to end up sloshed together in the environment even if an infection didn’t take place. Maybe an infected human visited the market and inadvertently deposited viral RNA near an animal’s crate.

    But an infected animal, with no third-party contamination, still seems by far the most plausible explanation for the samples’ genetic contents, several experts told me; other scenarios require contortions of logic and, more important, additional proof. Even prior to the reveal of the new data, Gronvall told me, “I think the evidence is actually more sturdy for COVID than it is for many others.” The strength of the data might even, in at least one way, best what’s available for SARS-CoV-1: Although scientists have isolated SARS-CoV-1-like viruses from a wet-market-traded mammal host, the palm civet, those samples were taken months after the outbreak began—and the viral variants found weren’t exactly identical to the ones in human patients. The versions of SARS-CoV-2 tugged out of several Huanan-market samples, meanwhile, are a dead ringer for the ones that sickened humans with COVID early on.

    The debate over SARS-CoV-2’s origins has raged for nearly as long as the pandemic itself—outlasting lockdowns, widespread masking, even the first version of the COVID vaccines. And as long as there is murkiness to cling to, it may never fully resolve. While evidence for an animal spillover has mounted over time, so too have questions about the possibility that the virus escaped from a laboratory. When President Biden asked the U.S. intelligence community to review the matter, four government agencies and the National Intelligence Council pointed to a natural origin, while two others guessed that it was a lab leak. (None of these assessments were made with high confidence; a bill passed in both the House and Senate would, 90 days after it becomes a law, require the Biden administration to declassify underlying intelligence.)

    If this new level of scientific evidence does conclusively tip the origins debate toward the animal route, it will be, in one way, a major letdown. It will mean that SARS-CoV-2 breached our borders because we once again mismanaged our relationship with wildlife—that we failed to prevent this epidemic for the same reason we failed, and could fail again, to prevent so many of the rest.

    Katherine J. Wu

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  • The COVID Question That Will Take Decades to Answer

    The COVID Question That Will Take Decades to Answer

    To be a newborn in the year 2023—and, almost certainly, every year that follows—means emerging into a world where the coronavirus is ubiquitous. Babies might not meet the virus in the first week or month of life, but soon enough, SARS-CoV-2 will find them. “For anyone born into this world, it’s not going to take a lot of time for them to become infected,” maybe a year, maybe two, says Katia Koelle, a virologist and infectious-disease modeler at Emory University. Beyond a shadow of a doubt, this virus will be one of the very first serious pathogens that today’s infants—and all future infants—meet.

    Three years into the coronavirus pandemic, these babies are on the leading edge of a generational turnover that will define the rest of our relationship with SARS-CoV-2. They and their slightly older peers are slated to be the first humans who may still be alive when COVID-19 truly hits a new turning point: when almost everyone on Earth has acquired a degree of immunity to the virus as a very young child.

    Read: Is COVID a common cold yet?

    That future crossroads might not sound all that different from where the world is currently. With vaccines now common in most countries and the virus so transmissible, a significant majority of people have some degree of immunity. And in recent months, the world has begun to witness the consequences of that shift. The flux of COVID cases and hospitalizations in most countries seems to be stabilizing into a seasonal-ish sine wave; disease has gotten, on average, less severe, and long COVID seems to be somewhat less likely among those who have recently gotten shots. Even the virus’s evolution seems to be plodding, making minor tweaks to its genetic code, rather than major changes that require another Greek-letter name.

    But today’s status quo may be more of a layover than a final destination in our journey toward COVID’s final form. Against SARS-CoV-2, most little kids have fared reasonably well. And as more babies have been born into a SARS-CoV-2-ridden world, the average age of first exposure to this coronavirus has been steadily dropping—a trend that could continue to massage COVID-19 into a milder disease. Eventually, the expectation is that the illness will reach a stable nadir, at which point it may truly be “another common cold,” says Rustom Antia, an infectious-disease modeler at Emory.

    The full outcome of this living experiment, though, won’t be clear for decades—well after the billions of people who encountered the coronavirus for the first time in adulthood are long gone. The experiences that today’s youngest children have with the virus are only just beginning to shape what it will mean to have COVID throughout a lifetime, when we all coexist with it from birth to death as a matter of course.

    At the beginning of SARS-CoV-2’s global tear, the coronavirus was eager to infect all of us, and we had no immunity to rebuff its attempts. But vulnerability wasn’t just about immune defenses: Age, too, has turned out to be key to resilience. Much of the horror of the disease could be traced to having not only a large population that lacked protection against the virus—but a large adult population that lacked protection against the virus. Had the entire world been made up of grade-schoolers when the pandemic arrived, “I don’t think it would have been nearly as severe,” says Juliet Pulliam, an infectious-disease modeler at Stellenbosch University, in South Africa.

    Across several viral diseases—polio, chicken pox, mumps, SARS, measles, and more—getting sick as an adult is notably more dangerous than as a kid, a trend that’s typically exacerbated when people don’t have any vaccinations or infections to those pathogens in their rearview. The manageable infections that strike toddlers and grade-schoolers may turn serious when they first manifest at older ages, landing people in the hospital with pneumonia, brain swelling, even blindness, and eventually killing some. When scientists plot mortality data by age, many curves bend into “a pretty striking J shape,” says Dylan Morris, an infectious-disease modeler at UCLA.

    The reason for that age differential isn’t always clear. Some of kids’ resilience probably comes from having a young, spry body, far less likely to be burdened with chronic medical conditions that raise severe disease risk. But the quick-wittedness of the young immune system is also likely playing a role. Several studies have found that children are much better at marshaling hordes of interferon—an immune molecule that armors cells against viruses—and may harbor larger, more efficient cavalries of infected-cell-annihilating T cells. That performance peaks sometime around grade school or middle school, says Janet Chou, a pediatrician at Boston Children’s Hospital. After that, our molecular defenses begin a rapid tumble, growing progressively creakier, clumsier, sluggish, and likelier to launch misguided attacks against the tissues that house them. By the time we’re deep into adulthood, our immune systems are no longer sprightly, or terribly well calibrated. When we get sick, our bodies end up rife with inflammation. And our immune cells, weary and depleted, are far less unable to fight off the pathogens they once so easily trounced.

    Whatever the explanations, children are far less likely to experience serious symptoms, or to end up in the hospital or the ICU after being infected with SARS-CoV-2. Long COVID, too, seems to be less prevalent in younger cohorts, says Alexandra Yonts, a pediatrician at Children’s National Hospital. And although some children still develop MIS-C, a rare and dangerous inflammatory condition that can appear weeks after they catch the virus, the condition “seems to have dissipated” as the pandemic has worn on, says Betsy Herold, the chief of pediatric infectious disease at the Children’s Hospital at Montefiore, in the Bronx.

    Should those patterns hold, and as the age of first exposure continues to fall, COVID is likely to become less intense. The relative mildness of childhood encounters with the virus could mean that almost everyone’s first infection—which tends, on average, to be more severe than the ones that immediately follow—could rank low in intensity, setting a sort of ceiling for subsequent bouts. That might make concentrating first encounters “in the younger age group actually a good thing,” says Ruian Ke, an infectious-disease modeler at Los Alamos National Laboratory.

    COVID will likely remain capable of killing, hospitalizing, and chronically debilitating a subset of adults and kids alike. But the hope, experts told me, is that the proportion of individuals who face the worst outcomes will continue to drop. That may be what happened in the aftermath of the 1918 flu pandemic, Antia, of Emory, told me: That strain of the virus stuck around, but never caused the same devastation again. Some researchers suspect that something similar may have even played out with another human coronavirus, OC43: After sparking a devastating pandemic in the 19th century, it’s possible that the virus no longer managed to wreak much more havoc than a common cold in a population that had almost universally encountered it early in life.

    Such a fate for COVID, though, isn’t a guarantee. The virus’s propensity to linger in the body’s nooks and crannies, sometimes causing symptoms that last many months or years, could make it an outlier among its coronaviral kin, says Melody Zeng, an immunologist at Cornell University. And even if the disease is likely to get better than what it is now, that is not a very high bar to clear.

    Some small subset of the population will always be naive to the virus—and it’s not exactly a comfort that in the future, that cohort will almost exclusively be composed of our kids. Pediatric immune systems are robust, UCLA’s Morris told me. But “robust is not the same as infallible.” Since the start of the pandemic, more than 2,000 Americans under the age of 18 have died from COVID—a small fraction of total deaths, but enough to make the disease a leading cause of death for children in the U.S. MIS-C and long COVID may not be common, but their consequences are no less devastating for the children who experience them. Some risks are especially concentrated among our youngest kids, under the age 5, whose immune defenses are still revving up, making them more vulnerable than their slightly older peers. There’s especially little to safeguard newborns just under six months, who aren’t yet eligible for most vaccines—including COVID shots—and who are rapidly losing the antibody-based protection passed down from their mothers while they were in the womb.

    A younger average age of first infection will also probably increase the total number of exposures people have to SARS-CoV-2 in a typical lifetime—each instance carrying some risk of severe or chronic disease. Ke worries the cumulative toll that this repetition could exact: Studies have shown that each subsequent tussle with the virus has the potential to further erode the functioning or structural integrity of organs throughout the body, raising the chances of chronic damage. There’s no telling how many encounters might push an individual past a healthy tipping point.

    Racking up exposures also won’t always bode well for the later chapters of these children’s lives. Decades from now, nearly everyone will have banked plenty of encounters with SARS-CoV-2 by the time they reach advanced age, Chou, from Boston Children’s Hospital, told me. But the virus will also continue to change its appearance, and occasionally escape the immunity that some people built up as kids. Even absent those evasions, as their immune systems wither, many older people may not be able to leverage past experiences with the disease to much benefit. The American experience with influenza is telling. Despite a lifetime of infections and available vaccines, tens of thousands of people typically die annually of the disease in the United States alone, says Ofer Levy, the director of the Precision Vaccines Program at Boston Children’s Hospital. So even with the expected COVID softening, “I don’t think we’re going to reach a point where it’s, Oh well, tra-la-la,” Levy told me. And the protection that immunity offers can have caveats: Decades of research with influenza suggest that immune systems can get a bit hung up on the first versions of a virus that they see, biasing them against mounting strong attacks against other strains; SARS-CoV-2 now seems to be following that pattern. Depending on the coronavirus variants that kids encounter first, their responses and vulnerability to future bouts of illness may vary, says Scott Hensley, an immunologist at the University of Pennsylvania.

    Read: Are our immune systems stuck in 2020?

    Early vaccinations—that ideally target multiple versions of SARS-CoV-2—could make a big difference in reducing just about every bad outcome the virus threatens. Severe disease, long COVID, and transmission to other children and vulnerable adults all would likely be “reduced, prevented, and avoided,” Chou told me. But that’s only if very young kids are taking those shots, which, right now, isn’t at all the case. Nor are they necessarily getting protection passed down during gestation or early life from their mothers, because many adults are not up to date on COVID shots.

    Some of these issues could, in theory, end up moot. A hundred or so years from now, COVID could simply be another common cold, indistinguishable in practice from any other. But Morris points out that this reality, too, wouldn’t fully spare us. “When we bother to look at the burden of the other human coronaviruses, the ones who have been with us for ages? In the elderly, it’s real,” he told me. One study found that a nursing-home outbreak of OC43—the purported former pandemic coronavirus—carried an 8 percent fatality rate; another, caused by NL63, killed three out of the 20 people who caught it in a long-term-care facility in 2017. These and other “mild” respiratory viruses also continue to pose a threat to people of any age who are immunocompromised.

    SARS-CoV-2 doesn’t need to follow in those footsteps. It’s the only human coronavirus against which we have vaccines—which makes the true best-case scenario one in which it ends up even milder than a common cold, because we proactively protect against it. Disease would not need to be as inevitable; the vaccine, rather than the virus, could be the first bit of intel on the disease that kids receive. Tomorrow’s children probably won’t live in a COVID-free world. But they could at least be spared many of the burdens we’re carrying now.

    Katherine J. Wu

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  • New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

    New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

    RESEARCH SUMMARY

    Publication: Nature Genetics https://www.nature.com/articles/s41588-023-01307-z

    Dana-Farber Cancer Institute author: Cigall Kadoch, PhD,

     

    Summary:

    A new class of oral drugs can inhibit a wide range of SARS-CoV-2 variants, researchers report, potentially identifying new antiviral agents providing broad activity against the constantly emerging new strains of the COVID-19 virus. The researchers discovered that the mammalian SWI/SNF (also called BAF) chromatin remodeling complex, a regulator of gene expression –controls the expression of the ACE2, the cellular receptor or “entry point” used by COVID-19 viruses.  When mSWI/SNF complexes were disrupted, the cell could no longer make ACE-2 receptor protein and became resistant to infection by any virus that uses that receptor. Kadoch’s work on mSWI/SNF complexes over the years has led to experimental drugs currently in phase 1 trials as anti-cancer agents. These oral drugs now are looking promising for use in COVID-19, since they can inhibit ACE2 activity and nearly completely block viral infection in multiple cell lines and human lung organoids.

    Impact:

    The formerly potent array of monoclonal antibody treatments for COVID-19 continue to lose their activity as new less-sensitve variants of the virus appear: indeed, one by one, they have gone off the market. The need for more broadly acting agents against new and drug-resistant viruses is great. With the identification of this new target – a druggable chromatin regulatory complex – inhibition of which prevents infection of host cells, Kadoch and co-author Craig Wilen, MD, PhD, of the Yale Cancer Center have found a promising novel approach to combating the constantly-changing SARS virus.

    Funding:

    This work was supported by NIH grants K08AI128043, Burroughs Wellcome Fund, Smith Family Foundation, Ludwig Family Foundation, Huffington Foundation, Mathers Foundation, Emergent Ventures Fast Grant, and NIH Director’s New Innovator Award 1DP2CA195762-01.

     

    Dana-Farber Cancer Institute

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  • COVID Vaccines Are Turning Into Flu Shots

    COVID Vaccines Are Turning Into Flu Shots

    For all the legwork that public-health experts have done over the past few years to quash comparisons between COVID-19 and the flu, there sure seems to be a lot of effort nowadays to equate the two. In an advisory meeting convened earlier today, the FDA signaled its intention to start doling out COVID vaccines just like flu shots: once a year in autumn, for just about everyone, ad infinitum. Whatever the brand, primary-series shots and boosters (which might no longer be called “boosters”) will guard against the same variants, making them interchangeable. Doses will no longer be counted numerically. “This will be a fundamental transition,” says Jason Schwartz, a vaccine policy expert at Yale—the biggest change to the COVID-vaccination regimen since it debuted.

    Hints of the annual approach have been dropping, not so subtly, for years. Even in the spring of 2021, Pfizer’s CEO was floating the idea of yearly shots; Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, teased it throughout 2022. This past September, Joe Biden officially endorsed it as “a new phase in our COVID-19 response,” and Ashish Jha, the White House’s COVID czar, memorably highlighted the convenience of combining a flu shot and a COVID shot into a single appointment: “I really believe this is why God gave us two arms.”

    Still, in today’s meeting, FDA officials were pushier than ever in their advocacy for the flu-ification of COVID vaccines. “We think that simplification of the vaccination regimen would contribute to easier vaccine deployment, better communication, and improved vaccine coverage,” Jerry Weir, the FDA’s director of the division of viral products, said at the meeting. The timing is important: After renewing the U.S.’s pandemic-emergency declaration earlier this month, the Biden administration seems set to allow its expiration this coming April. That makes the present moment awfully convenient for repackaging a chaotic, crisis-caliber vaccination paradigm as a scheduled, seasonal, normal-seeming one. A once-a-year strategy, modeled on a routine recommendation, suggests that “we’re no longer in emergency mode,” says Maria Sundaram, a vaccine researcher at the Marshfield Clinic Research Institute. Or at least, that’s the message that the public is likely to hear.

    But federal regulators may be trying to fit a COVID-shaped peg into a flu-shaped hole. The experts I spoke with largely agreed: Eventually, someday, annual autumn shots for COVID “will probably be sufficient,” says Gregory Poland, a vaccinologist at Mayo Clinic. “Are we ready for that yet? I’m not sure that’s the case at all.”

    Even in the short term, COVID-vaccination tactics need a revamp. “It’s clear above all that the current approach isn’t working,” Schwartz told me. Despite abundant supply, demand for COVID boosters in the U.S. has been abysmal—and interest seems to be declining with each additional dose. Last fall’s bivalent shot has reached the arms of only 15 percent of Americans; even among adults over 65—a majority of whom sign up for flu shots each fall—the vaccination rate hasn’t yet reached 40 percent.

    For most of the time that COVID shots have been around, figuring out when to get them has been a hassle, with different guidelines and requirements that depend on age, sex, risk factors, vaccination history, and more. Pharmacies have had to stock an absurd number of vials and syringes to accommodate the various combinations of brands and dose sizes; record-keeping on flimsy paper cards has been a total joke. “I do this for a living, and I can barely keep track,” Schwartz said. Recommendations on the proper timing and number of doses have also changed so many times that many Americans have simply checked out. After the bivalent recipe debuted, polls found that an alarming proportion of people didn’t even know the shot was available to them.

    Streamlining COVID-vaccine recommendations will remove a lot of that headache, Sundaram told me. Most people would need to keep only one mantra in mind—one dose, each fall—and could top off their flu and COVID immunity at the same time. Burdens on pharmacies and clinics would be lower, and communication would be far easier—a change that could make an especially big difference for those with children, among whom COVID-vaccine uptake has been the lowest. “It’ll be more scheduled, more systematic,” says Charlotte Hobbs, a pediatric infectious-disease specialist at the University of Mississippi Medical Center. COVID shots could simply be offered at annual well-child visits, she told me. “It’s something we already know works well.”

    The advantages of a flu-ified COVID shot aren’t just about convenience. If we have to shoehorn COVID vaccines into an existing paradigm, Sundaram told me, influenza’s is the best candidate. SARS-CoV-2, like the flu, is excellent at altering itself to dodge our defenses; it spreads readily in winter; and our immunity to infection tends to fade rather quickly. All of that adds up to a need for regularly updated shots. Such a system has been in place for decades for the flu: At the end of each winter, a panel of experts convenes to select the strains that should be targeted by the next formulation; manufacturers spend the next several months whipping up big batches in time for an autumn-ish rollout. The pipeline depends on a global surveillance system for flu viruses, as well as regular surveys of antibody levels in the community to suss out which strains people are still protected against. The premise has been so well vetted by now that researchers can skip the chore of running large-scale clinical trials to determine the efficacy and safety of each new, updated recipe.

    But a seasonal strategy works best for a seasonal virus—and SARS-CoV-2 just isn’t there yet, says Hana El Sahly, an infectious-disease physician at Baylor College of Medicine. Though flu viruses tend to hop between the globe’s hemispheres, alternately troubling the north and the south during their respective cold months, this new coronavirus has yet to confine its spread to one part of the calendar. (Marks, of the FDA, tried to address this concern at today’s meeting, asserting that “we’re starting to see some seasonality” and that fall was indeed the very sensible for an annual rollout.) SARS-CoV-2 has also been spitting out concerning variants and subvariants at a faster rate than the flu (and flu shots already have a hard time keeping up with evolution). The FDA’s new proposal suggests picking SARS-CoV-2 variants in June to have a vaccine ready by September, a shorter timeline than is used for flu. That still might not be fast enough: “By the time we detect a variant, it will have ripped through the global population and, in a few more weeks, died down,” El Sahly told me. The world got a preview of this problem with last year’s bivalent shot, which overlapped with the dominance of its target subvariants for only a couple of months. A flu model for COVID would make more sense “if we had stable, predictable dynamics,” says Avnika Amin, a vaccine epidemiologist at Emory University. “I don’t think we’re at that point.”

    Murkiness around vaccine effectiveness makes this transition complicated too. Experts told me that it’s gotten much more difficult to tell how well our COVID vaccines are working, and for how long, fueling debates over how often they should be given and how often their composition should change. Many people have now been infected by the virus multiple times, which can muddy calculations of vaccine effectiveness; better treatments also alter risk profiles. And many researchers told me they’re concerned that the data shortcuts we use for flu—measures of antibodies as a proxy for immune protection—just won’t fly for COVID shots. “We need better clinical data,” El Sahly told me. In their absence, the hasty adoption of a flu framework could lead to our updating and distributing COVID shots too often, or not often enough.

    A flu-ish approach also wouldn’t fix all of the COVID vaccines’ problems. Today’s discussion suggested that, even if a new COVID-shot strategy change goes through, officials will still need to recommend several different dose sizes for several different age groups—a more complex regimen than flu’s—and may advise additional injections for those at highest risk. At the same time, COVID shots would continue to be more of a target for misinformation campaigns than many other vaccines and, at least in the case of mRNA-based injections, more likely to cause annoying side effects. These issues and others have driven down interest—and simply pivoting to the flu paradigm “is not going to solve the uptake problem,” says Angela Shen, a vaccine-policy expert at Children’s Hospital of Philadelphia.

    Perhaps the greatest risk of making COVID vaccines more like flu shots is that it could lead to more complacency. In making the influenza paradigm a model, we also threaten to make it a ceiling. Although flu shots are an essential, lifesaving public-health tool, they are by no means the best-performing vaccines in our roster. Their timeline is slow and inefficient; as a result, the formulations don’t always match circulating strains. Already, with COVID, the world has struggled to chase variants with vaccines that simply cannot keep up. If we move too quickly to the fine-but-flawed framework for flu, experts told me, it could disincentivize research into more durable, more variant-proof, less side-effect-causing COVID shots. Uptake of flu vaccines has never been stellar, either: Just half of Americans sign up for the shots each year—and despite years of valiant efforts, “we still haven’t figured out how to consistently improve that,” Amin told me.

    Whenever the COVID-emergency declaration expires, vaccination will almost certainly have to change. Access to shots may be imperiled for tens of millions of uninsured Americans; local public-health departments may end up with even fewer resources for vaccine outreach. A flu model might offer some improvements over the status quo. But if the downsides outweigh the pluses, Poland told me, that could add to the erosion of public trust. Either way, it might warp attitudes toward this coronavirus in ways that can’t be reversed. At multiple points during today’s meeting, FDA officials emphasized that COVID is not the flu. They’re right: COVID is not the flu and never will be. But vaccines can sometimes become a lens through which we view the dangers they fight. By equating our frontline responses to these viruses, the U.S. risks sending the wrong message—that they carry equal threat.

    Katherine J. Wu

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  • Trying to Stop Long COVID Before It Even Starts

    Trying to Stop Long COVID Before It Even Starts

    Three years into the global fight against SARS-CoV-2, the arsenal to combat long COVID remains depressingly bare. Being vaccinated seems to reduce people’s chances of developing the condition, but the only surefire option for avoiding long COVID is to avoid catching the coronavirus at all—a proposition that feels ever more improbable. For anyone who is newly infected, “we don’t have any interventions that are known to work,” says Akiko Iwasaki, an immunologist and long-COVID researcher at Yale.

    Some researchers are hopeful that the forecast might shift soon. A pair of recent preprint studies, both now under review for publication in scientific journals, hint that two long-COVID-preventing pills might already be on our pharmacy shelves: the antiviral Paxlovid and metformin, an affordable drug commonly used for treating type 2 diabetes. When taken early in infection, each seems to at least modestly trim the chance of developing long COVID—by 42 percent, in the case of metformin. Neither set of results is a slam dunk. The Paxlovid findings did not come out of a clinical trial, and were focused on patients at high risk of developing severe, acute COVID; the metformin data did come out of a clinical trial, but the study was small. When I called more than half a dozen infectious-disease experts to discuss them, all used hopeful, but guarded, language: The results are “promising,” “intriguing”; they “warrant further investigation.”

    At this point, though, any advance at all feels momentous. Long COVID remains the pandemic’s biggest unknown: Researchers still can’t even agree on its prevalence or the features that define it. What is clear is that millions of people in the United States alone, and countless more worldwide, have experienced some form of it, and more are expected to join them. “We’ve already seen early data, and we’ll continue to see data, that that will emphasize the impact that long COVID has on our society, on quality of life, on productivity, on our health system and medical expenditures,” says Susanna Naggie, an infectious-disease physician and COVID-drug researcher at Duke University. “This needs to be a high priority,” she told me. Researchers have to trim long COVID incidence as much as possible, as soon as possible, with whatever safe, effective options they can.

    By now, news of the inertia around preventive long-COVID therapies may not come as much of a shock. Interventions that stop disease from developing are, on the whole, a neglected group; big, blinded, placebo-controlled clinical trials—the industry gold standard—usually look to investigate potential treatments, rather than drugs that might keep future illness at bay. It’s a bias that makes research easier and faster; it’s a core part of the American medical culture’s reactive approach to health.

    Read: Long COVID has forced a reckoning for one of medicine’s most neglected diseases

    For long COVID, the terrain is even rougher. Researchers are best able to address prevention when they understand a disease’s triggers, the source of its symptoms, and who’s most at risk. That intel provides a road map, pointing them toward specific bodily systems and interventions. The potential causes of COVID, though, remain murky, says Adrian Hernandez, a cardiologist and clinical researcher at Duke. Years of research have shown that the condition is quite likely to comprise a cluster of diverse syndromes with different triggers and prognoses, more like a category (e.g., “cancer”) than a singular disease. If that’s the case, then a single preventive treatment shouldn’t be expected to cut its rates for everyone. Without a universal way to define and diagnose the condition, researchers can’t easily design trials, either. Endpoints such as hospitalization and death tend to be binary and countable. Long COVID operates in shades of gray.

    Still, some scientists might be making headway with vetted antiviral drugs, already known to slash the risk of developing severe COVID-19. A subset of long-COVID cases could be caused by bits of virus that linger in the body, prompting the immune system to wage an extended war; a drug that clears the microbe more quickly might lower the chances that any part of the invader sticks around. Paxlovid, which interferes with SARS-CoV-2’s ability to copy itself inside of our cells, fits that bill. “The idea here is really nipping it in the bud,” says Ziyad Al-Aly, a clinical epidemiologist and long-COVID researcher at Washington University in St. Louis, who led the recent Paxlovid work.

    Paxlovid has yet to hit the scientific jackpot: proof from a big clinical trial that shows it can prevent long COVID in newly infected people. But Al-Aly’s study, which pored over the electronic medical records of more than 56,000 high-risk patients, offers some early optimism. People who took the pills, he and his colleagues found, were 26 percent less likely to report lingering symptoms three months after their symptoms began than those who didn’t.

    Read: Inside the mind of an anti-Paxxer

    The pills’ main benefit remains the prevention of severe, acute disease. (In the recent study, Paxlovid-takers were also 30 percent less likely to be hospitalized and 48 percent less likely to die.) Al-Aly expects that the drug’s effectiveness at preventing long COVID—if it’s confirmed in other populations—will be “modest, not huge.” Though the two functions could yet be linked: Some long-COVID cases may result from severe infections that damage tissues so badly that the body struggles to recover. And should Paxlovid’s potential pan out, it could help build the case for testing other SARS-CoV-2 antivirals. Al-Aly and his colleagues are currently working on a similar study into molnupiravir. “The early results are encouraging,” he told me, though “not as robust as Paxlovid.” (Another study, run by other researchers, that followed hospitalized COVID patients found those who took remdesivir were less likely to get long COVID, but a later randomized clinical trial didn’t bear that out.)

    A clinical trial testing Paxlovid’s preventive potency against long COVID is still needed. Kit Longley, a spokesperson for Pfizer, told me in an email that the company doesn’t currently have one planned, though it is “continuing to monitor data from our clinical studies and real-world evidence.” (The company is collaborating with a research group at Stanford to study Paxlovid in new clinical contexts, but they’re looking at whether the pills  might treat long COVID that’s already developed. The RECOVER trial, a large NIH-funded study on long COVID, is also focusing its current studies on treatment.) But given the meager uptake rates for Paxlovid even among those in high-risk groups, Al-Aly thinks his new data could already serve a useful purpose: providing people with extra motivation to take the drug.

    The case for adding metformin to the anti-COVID tool kit might be a bit muddier. The drug isn’t the most intuitive medication to deploy against a respiratory virus, and despite its widespread use among diabetics, its exact effects on the body remain nebulous, says Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital. But there are many reasons to believe it might be useful. Some research has shown that metformin can mess with the manufacture of viral proteins inside of human cells, Bramante told me, which may impede the ability of SARS-CoV-2 and other pathogens to reproduce. The drug also appears to rev up the disease-dueling powers of certain immune cells, and to stave off inflammation. Studies have shown that metformin can improve responses to certain vaccinations in humans and rodents, and researchers have found that people taking the drug seem less likely to get seriously sick from influenza. Even the diabetes-coronavirus connection may not be so tenuous: Metabolic disease is a risk factor for severe COVID; infection itself can put blood-sugar levels on the fritz. It’s certainly plausible that having a metabolically altered body, Schultz-Cherry told me, could make infections worse.

    Read: The promising treatment we’re not even trying for long COVID

    But the evidence that metformin helps prevent long COVID remains sparse. Carolyn Bramante, the scientist who led the metformin study, told me that when her team first set out in 2020 to investigate the drug’s effects on SARS-CoV-2 infections in a randomized, clinical trial, long COVID wasn’t really on their radar. Like many others in their field, they were hoping to repurpose established medicines to keep infected people out of the hospital; early studies of metformin—as well as the two other drugs in their trial, the antidepressant fluvoxamine and the antiparasitic ivermectin—hinted that they’d work. Ironically, two years later, their story flipped around. A large analysis, published last summer, showed that none of the three drugs were stellar at preventing severe COVID in the short term—a disappointing result (though Bramante contends that their data still indicate that metformin does some good). Then, when Bramante and her colleagues examined their data again, they found that study participants that had taken metformin for two weeks around the start of their illness were 42 percent less likely to have a long-COVID diagnosis from their doctor nearly a year down the road. David Boulware, an infectious-disease physician who helped lead the work, considers that degree of reduction pretty decent: “Is it 100 percent? No,” he told me. “But it’s better than zero.”

    Metformin may well prove to prevent long COVID but not acute, severe COVID (or vice versa). Plenty of people who never spend time in the hospital can still end up developing chronic symptoms. And Iwasaki points out that the demographics of long-haulers and people who get severe COVID don’t really overlap; the latter skew older and male. In the future, early-infection regimens may be multipronged: antivirals, partnered with metabolic drugs, in the hopes of keeping symptoms both mild and short-lived.

    But researchers are still a long way off from delivering that reality. It’s not yet clear, for instance, whether the drugs work additively when combined, Boulware told me. Nor is it a given that they’ll work across different demographics—age, vaccination status, risk factors, and more. Bramante and Boulware’s study cast a decently wide net: Although everyone enrolled in the trial was overweight or obese, many were young and healthy; a few were even pregnant. The study was not enormous, though—about 1,000 people. It also relied on patients’ individual doctors to deliver long-COVID diagnoses, likely leading to some inconsistencies, so other studies that follow up in the future could find different results. For now, this isn’t enough to “mean we should run out and use metformin,” Schultz-Cherry, who has been battling long COVID herself, told me.

    Other medications could still fill the long-COVID gaps. Hernandez, the Duke cardiologist, is hopeful that one of his ongoing clinical trials, ACTIV-6, might provide answers soon. He and his team are testing whether any of several drugs—including ivermectin, fluvoxamine, the steroid fluticasone, and, as a new addition, the anti-inflammatory montelukast—might cut down on severe, short-term COVID. But Hernandez and his colleagues, Naggie among them, appended a check-in at the 90-day mark, when they’ll be asking their patients whether they’re experiencing a dozen or so symptoms that could hint at a chronic syndrome.

    That check-in questionnaire won’t capture the full list of long-COVID symptoms, now more than 200 strong. Still, the three-month benchmark could give them a sense of where to keep looking, and for how long. Hernandez, Naggie, and their colleagues are considering whether to extend their follow-up period to six months, maybe farther. The need for long-COVID prevention, after all, will only grow as the total infection count does. “We’re not going to get rid of long COVID anytime soon,” Iwasaki told me. “The more we can prevent onset, the better off we are.”

    Katherine J. Wu

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  • Consider Armadillo COVID

    Consider Armadillo COVID

    This past spring, Amanda Goldberg crouched in the leafy undergrowth of a southwestern Virginia forest and attempted to swab a mouse for COVID. No luck; its nose was too tiny for her tools. “You never think about nostrils until you start having to swab an animal,” Goldberg, a conservation biologist at Virginia Tech University, told me. Larger-nosed creatures that she and her team had trapped, such as raccoons and foxes, had no issue with nose swabs—but for mice, throat samples had to do. The swabs fit reasonably well into their mouths, she said, though they endured a fair bit of munching.

    Goldberg’s throat-swabbing endeavors were part of a study she and her colleagues devised to answer an unexplored question: How common is COVID in wildlife? Of the 333 forest animals her team swabbed around Blacksburg, Virginia, spanning 18 species, one—an opossum—tested positive. This was to be expected, Goldberg said; catching a wild animal that happened to have an active infection right when it was swabbed was like finding Waldo. But the researchers also collected blood samples, and those were more telling about whether the animals had experienced previous bouts with COVID. Analysis by the Molecular Diagnostics Lab and the Fralin Biomedical Research Institute at Virginia Tech revealed antibodies across 24 animals spanning six species, including the opossum, the Eastern gray squirrel, and two types of mice. “Our minds were blown,” Goldberg said. “It was basically every species we sent” to the lab.

    That animals can get COVID is one of the earliest things we learned about the virus. Despite the endless debate over its origins, SARS-CoV-2 most likely jumped from an animal through an intermediate host to humans in Wuhan. Since then, it has since spread back to a range of animals. People have passed it to household pets, such as dogs and cats, and to a Disney movie’s worth of beasts, including lions, hippos, hyenas, tigers, mink, and hamsters. Three years into the pandemic, animals are still falling sick with COVID, just as we are. COVID is likely circulating more widely in animals than we are aware of, Edward Holmes, a biologist at the University of Sydney, told me. “In all my 30-plus years of doing work on this subject, I have never seen a virus that can infect so many animal species,” he said. More than 500 other mammal species are predicted to be highly susceptible to infection.

    Given that most people nowadays aren’t fretting too much about human-to-human spread, it makes sense that animal-to-human spread has largely been forgotten. But even when there are so many other pandemic concerns, animal COVID can’t be ignored. The consequences of sustained animal transmission are exactly the same as they are in people: The more COVID spreads, the more opportunities the virus has to evolve into new variants. What’s most alarming is the chance that one of those variants could spill back into humans. As we’ve known since the pandemic started, SARS-CoV-2 is not a human virus, but one that can infect multiple animals, including humans. As long as animals are still getting COVID, we’re not out of the doghouse either.

    Perhaps part of the reason COVID in animals has been overlooked—apart from the fact that they’re not people—is that most species don’t seem to get very sick. Animals that have gotten infected generally exhibit mild symptoms—typically some coughing and sluggishness, as in pumas and lions. But our research has gone only fur-deep. “We certainly can’t ask them, ‘Are you feeling headaches, or sluggish?’” said Goldberg, who worries about long-term or invisible symptoms going undiagnosed in species. And so animal COVID has lingered unchecked, increasing the chances that it could mean something bad for us.

    The good news is that the overall risk of getting COVID from animals is considered low, according to the CDC. This is partly explained by evolutionary theory, which predicts that most variants that emerge in an animal population will have adapted to become better at infecting the host animal—not us. But some of them, strictly by chance, “could be highly transmissible or virulent in humans,” Holmes said. “It’s an unpredictable process.” His concern is not that animals will start infecting people en masse—your neighbors are far likelier to do that than raccoons—but that in animals, SARS-CoV-2 could form new variants that can spill over into people. Some scientists believe that Omicron emerged this way in mice, though evidence remains scant.

    A troubling sign is that there’s already some evidence that COVID has made its way from humans to animals, where it mutated, and then made its way back into humans. Take white-tailed deer, by now a well-known COVID host. Every fall, hunters take to the golden meadows and reddening forests of southwestern Ontario to shoot the deer, giving researchers an opportunity to test some of the hunted animals for COVID. The species has been infected with the same variants circulating widely in humans—a handful of Staten Island deer caught Omicron last winter, for example—which suggests that people are infecting them. How the deer get infected still isn’t clear: Extended face time with humans, nosing around in trash, or slurping up our wastewater are all possibilities.

    The researchers in Canada found not only that some of the animals tested positive, but also that the variant they carried had never before been seen in humans, indicating that the virus had been spreading and mutating within the population for a long time, Brad Pickering, a research scientist for the Canadian government who studied the deer, told me. In fact, the new variant is among the most evolutionarily divergent ones identified so far. But despite its differences, it appeared to have infected at least one person who had interacted with deer the week before falling ill. “We can’t make a direct link between them,” Pickering said, but the fact that such a highly diverged deer variant was detected in a human is very suggestive of how that person got sick.

    This research adds to the small but growing body of evidence that the COVID we spread to animals could come back to bite us. Fortunately, this particular spillback does not appear to have had serious consequences for humans; rogue deer variants don’t seem to be circulating in southern Canada. But this is not the sole documented instance of animal-to-human spread: People have been infected by mink in the Netherlands, hamsters in Hong Kong, and a cat in Thailand. Other spillbacks have probably occurred and gone unnoticed. So far, no data show that the animal variants that have spread to humans are more dangerous for us. Even if a potential animal variant isn’t the next Omicron, it could still be better at dodging our existing treatments and vaccines, Pickering said.

    But there is also, frankly, a lack of data. Local wildlife-surveillance efforts led by researchers like Goldberg and Pickering are ongoing, but they do not exist in most countries, Holmes said. An international database of known animal infections, maintained by Complexity Science Hub Vienna, is a promising start. An interactive map shows the locations of previously infected animals, including large hairy armadillos (Argentina), manatees (Brazil), and cats (everywhere). At the very least, with animal COVID, “we need to know what species it’s in, in what abundance, and genetically, what those variants look like,” Holmes said. “It’s absolutely critical to know where [the virus] is going.” Without this, there is no way of knowing how often spillback occurs and whether it puts humans at risk. And we can’t tell whether new COVID variants are also putting animals in danger, Goldberg said; a devastating Omicron-like variant could emerge in their populations too.

    The steps we need to take to mitigate the animal-COVID problem—and prevent other zoonotic diseases from jumping into humans—are clear, even if they don’t seem to be happening. Eliminating wet markets where wild animals are sold is an obvious preventive measure, but it has been difficult to implement because the livelihoods and diets of many people, especially in the global South, depend on them. As climate change and land development decimate even more habitats, wildlife will be forced into ever-closer quarters with us, fostering an even more efficient exchange of viruses between species. Unlike mask wearing and other straightforward options for curbing the human spread of COVID, preventing its transmission to, from, and among animals will require major upheavals to the way our societies run, likely far greater than we are willing to commit to.

    Humans tend to act like COVID ends up afflicting us after traveling through a long chain of species. But to think so is like living in the Middle Ages, Holmes said, when the Earth was considered the center of the universe. As we learned then, we are not that important: Humans are but a node in an immense network of species that viruses move through in many directions. Just as animal viruses infect us, human viruses can spread to animals (measles, for example, kills a variety of great apes). There are definitely bigger problems than animal COVID—no one needs to hunker down for fear of sneezing deer—but as long as animals keep getting infected, we can’t overlook what that means for us. Paying attention to animal COVID often starts with a single swab—and a snout to stick it in.

    Yasmin Tayag

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  • Is COVID a Common Cold Yet?

    Is COVID a Common Cold Yet?

    At the start of the coronavirus pandemic, one of the worst things about SARS-CoV-2 was that it was so new: The world lacked immunity, treatments, and vaccines. Tests were hard to come by too, making diagnosis a pain—except when it wasn’t. Sometimes, the symptoms of COVID got so odd, so off-book, that telling SARS-CoV-2 from other viruses became “kind of a slam dunk,” says Summer Chavez, an emergency physician at the University of Houston. Patients would turn up with the standard-issue signs of respiratory illness—fever, coughing, and the like—but also less expected ones, such as rashes, diarrhea, shortness of breath, and loss of taste or smell. A strange new virus was colliding with people’s bodies in such unusual ways that it couldn’t help but stand out.

    Now, nearly three years into the crisis, the virus is more familiar, and its symptoms are too. Put three sick people in the same room this winter—one with COVID, another with a common cold, and the third with the flu—and “it’s way harder to tell the difference,” Chavez told me. Today’s most common COVID symptoms are mundane: sore throat, runny nose, congestion, sneezing, coughing, headache. And several of the wonkier ones that once hogged headlines have become rare. More people are weathering their infections with their taste and smell intact; many can no longer remember when they last considered the scourge of “COVID toes.” Even fever, a former COVID classic, no longer cracks the top-20 list from the ZOE Health Study, a long-standing symptom-tracking project based in the United Kingdom, according to Tim Spector, an epidemiologist at King’s College London who heads the project. Longer, weirder, more serious illness still manifests, but for most people, SARS-CoV-2’s symptoms are getting “pretty close to other viruses’, and I think that’s reassuring,” Spector told me. “We are moving toward a cold-like illness.”

    That trajectory has been forecast by many experts since the pandemic’s early days. Growing immunity against the coronavirus, repeatedly reinforced by vaccines and infections, could eventually tame COVID into a sickness as trifling as the common cold or, at worst, one on par with the seasonal flu. The severity of COVID will continue to be tempered by widespread immunity, or so this thinking goes, like a curve bending toward an asymptote of mildness. A glance at the landscape of American immunity suggests that such a plateau could be near: Hundreds of millions of people in the U.S. have been vaccinated multiple times, some even quite recently with a bivalent shot; many have now logged second, third, and fourth infections with the virus. Maybe, just maybe, we’re nearing the level of cumulative exposure at which COVID gets permanently more chill. Then again? Maybe not—and maybe never.

    Read: What does it mean to care about COVID anymore?

    The recent trajectory of COVID, at least, has been peppered with positive signs. On average, symptoms have migrated higher up the airway, sparing several vulnerable organs below; disease has gotten shorter and milder, and rates of long COVID seem to be falling a bit. Many of these changes roughly coincided with the arrival of Omicron in the fall of 2021, and part of the shift is likely attributable to the virus itself: On the whole, Omicron and its offshoots seem to prefer infecting cells in the nose and throat over those in the lungs. But experts told me the accumulation of immune defenses that preceded and then accompanied that variant’s spread are almost certainly doing more of the work. Vaccination and prior infection can both lay down protections that help corral the virus near the nose and mouth, preventing it from spreading to tissues elsewhere. “Disease is really going to differ based on the compartment that’s primarily infected,” says Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital. As SARS-CoV-2 has found a tighter anatomical niche, our bodies have become better at cornering it.

    With the virus largely getting relegated to smaller portions of the body, the pathogen is also purged from the airway faster and may be less likely to be passed to someone else. On the individual level, a sickness that might have once unfurled into pneumonia now gets subdued into barely perceptible sniffles and presents less risk to others; on the population scale, rates of infection, hospitalization, and death go down.

    This is how things usually go with respiratory viruses. Repeat tussles with RSV tend to get progressively milder; post-vaccination flu is usually less severe. The few people who catch measles after getting their shots are less likely to transmit the virus, and they tend to experience such a trivial course of sickness that their disease is referred to by a different name, “modified” measles, says Diane Griffin, a virologist and an immunologist at Johns Hopkins University.

    It’s good news that the median case of COVID diminished in severity and duration around the turn of 2022, but it’s a bit more sobering to consider that there hasn’t been a comparably major softening of symptoms in the months since. The full range of disease outcomes—from silent infection all the way to long-term disability, serious disease, and death—remains in play as well, for now and the foreseeable future, Schultz-Cherry told me. Vaccination history and immunocompromising conditions can influence where someone falls on that spectrum. So too can age as well as other factors such as sex, genetics, underlying medical conditions, and even the dose of incoming virus, says Patricia García, a global-health expert at the University of Washington.

    New antibody-dodging viral variants could still show up to cause more severe disease even among the young and healthy, as occasionally happens with the flu. The BA.2 subvariant of Omicron, which is more immune-evasive than its predecessor BA.1, seemed to accumulate more quickly in the airway, and it sparked more numerous and somewhat gnarlier symptoms. Data on more recent Omicron subvariants are still being gathered, but Shruti Mehta, an epidemiologist at Johns Hopkins, says she’s seen some hints that certain gastrointestinal symptoms, such as vomiting, might be making a small comeback.

    Read: Will we get Omicron’d again?

    All of this leaves the road ahead rather muddy. If COVID will be tamed one day into a common cold, that future definitely hasn’t been realized yet, says Yonatan Grad, an epidemiologist at Harvard’s School of Public Health. SARS-CoV-2 still seems to spread more efficiently and more quickly than a cold, and it’s more likely to trigger severe disease or long-term illness. Still, previous pandemics could contain clues about what happens next. Each of the past century’s flu pandemics led to a surge in mortality that wobbled back to baseline after about two to seven years, Aubree Gordon, an epidemiologist at the University of Michigan, told me. But SARS-CoV-2 isn’t a flu virus; it won’t necessarily play by the same epidemiological rules or hew to a comparable timeline. Even with flu, there’s no magic number of shots or past infections that’s known to mollify disease—“and I think we know even less about how you build up immunity to coronaviruses,” Gordon said.

    The timing of when and how those defenses manifest could matter too. Almost everyone has been infected by the flu or at least gotten a flu shot by the time they reach grade school; SARS-CoV-2 and COVID vaccines, meanwhile, arrived so recently that most of the world’s population met them in adulthood, when the immune system might be less malleable. These later-in-life encounters could make it tougher for the global population to reach its severity asymptote. If that’s the case, we’ll be in COVID limbo for another generation or two, until most living humans are those who grew up with this coronavirus in their midst.

    COVID may yet stabilize at something worse than a nuisance. “I had really thought previously it would be closer to common-cold coronaviruses,” Gordon told me. But severity hasn’t declined quite as dramatically as she’d initially hoped. In Nicaragua, where Gordon has been running studies for years, vaccinated cohorts of people have endured second and third infections with SARS-CoV-2 that have been, to her disappointment, “still more severe than influenza,” she told me. Even if that eventually flips, should the coronavirus continue to transmit this aggressively year-round, it could still end up taking more lives than the flu does—as is the case now.

    Wherever, whenever a severity plateau is reached, Gordon told me that our arrival to it can be confirmed only in hindsight, “once we look back and say, ‘Oh, yeah, it’s been about the same for the last five years.’” But the data necessary to make that call are getting harder to collect as public interest in the virus craters and research efforts to monitor COVID’s shifting symptoms hit roadblocks. The ZOE Health Study lost its government funding earlier this year, and its COVID-symptom app, which engaged some 2.4 million regular users at its peak, now has just 400,000—some of whom may have signed up to take advantage of newer features for tracking diet, sleep, exercise, and mood. “I think people just said, ‘I need to move on,’” Spector told me.

    Mehta, the Johns Hopkins epidemiologist, has encountered similar hurdles in her COVID research. At the height of the Omicron wave, when Mehta and her colleagues were trying to find people for their community studies, their rosters would immediately fill up past capacity. “Now we’re out there for weeks” and still not hitting the mark, she told me. Even weekly enrollment for their long-COVID study has declined. Sign-ups do increase when cases rise—but they drop off especially quickly as waves ebb. Perhaps, in the view of some potential study volunteers, COVID has, ironically, become like a common cold, and is thus no longer worth their time.

    For now, researchers don’t know whether we’re nearing the COVID-severity plateau, and they’re worried it will get only more difficult to tell. Maybe it’s for the best if the mildness asymptote is a ways off. In the U.S. and elsewhere, subvariants are still swirling, bivalent-shot uptake is still stalling, and hospitalizations are once more creeping upward as SARS-CoV-2 plays human musical chairs with RSV and flu. Abroad, inequities in vaccine access and quality—and a zero-COVID policy in China that stuck around too long—have left gaping immunity gaps. To settle into symptom stasis with this many daily deaths, this many off-season waves, this much long COVID, and this pace of viral evolution would be grim. “I don’t think we’re quite there yet,” Gordon told me. “I hope we’re not there yet.”

    Katherine J. Wu

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  • Will Flu and RSV Always Be This Bad?

    Will Flu and RSV Always Be This Bad?

    In the Northern Hemisphere, this year’s winter hasn’t yet begun. But Melissa J. Sacco, a pediatric-intensive-care specialist at UVA Health, is already dreading the arrival of the one that could follow.

    For months, the ICU where Sacco works has been overflowing with children amid an early-arriving surge of respiratory infections. Across the country, viruses such as RSV and flu, once brought to near-record lows by pandemic mitigations, have now returned in force, all while COVID-19 continues to churn and the health-care workforce remains threadbare. Most nights since September, Sacco told me, her ICU has been so packed that she’s had to turn kids away “or come up with creative ways to manage patients in emergency rooms or emergency departments,” where her colleagues are already overwhelmed and children more easily slip through the cracks. The team has no choice: There’s nowhere else for critically ill kids to go.

    Similar stories have been pouring in from around the nation for weeks. I recently spoke with a physician in Connecticut who called this “by far the worst spike in illness I’ve seen in 20 years”; another in Maryland told me, “There have been days when there is not an ICU bed to be found anywhere in the mid-Atlantic.” About three-quarters of the country’s pediatric hospital beds are full; to accommodate overflow, some hospitals have set up tents outside their emergency department or contemplated calling in the National Guard. Last week, the Children’s Hospital Association and the American Academy of Pediatrics asked the Biden administration to declare a national emergency. And experts say there’s no end to the crisis in sight. When Sacco imagines a similar wave slamming her team again next fall, “I get that burning tear feeling in the back of my eyes,” she told me. “This is not sustainable.”

    Read: The worst pediatric-care crisis in decades

    The experts I spoke with are mostly optimistic that these cataclysmic infection rates won’t become an autumn norm. But they also don’t yet fully understand the factors that have been driving this year’s surge, making it tough to know with certainty whether we’re due for an encore.

    One way or another, COVID has certainly thrown the typical end-of-year schedule out of whack. Respiratory viruses typically pick up speed in late fall, peak in mid-to-late winter, and then bow out by the spring; they often run in relay, with one microbe surging a bit before another. This year, though, nearly every pathogen arrived early, cresting in overlapping waves. “Everything is happening at once,” says Kathryn Edwards, a pediatrician and vaccinologist at Vanderbilt University. November isn’t yet through, and RSV has already sent infant hospitalizations soaring past pre-pandemic norms. Flu-hospitalization rates are also at their worst in more than a decade; about 30 states, plus D.C. and Puerto Rico, are reporting high or very high levels of the virus weeks before it usually begins its countrywide climb. And the country’s late-summer surge in rhinovirus and enterovirus has yet to fully abate. “We just haven’t had a break,” says Asuncion Mejias, a pediatrician at Nationwide Children’s Hospital.

    Previous pandemics have had similar knock-on effects. The H1N1-flu pandemic of 2009, for example, seems to have pushed back the start of the two RSV seasons that followed; seasonal flu also took a couple of years to settle back into its usual rhythms, Mejias told me. But that wonky timetable wasn’t permanent. If the viral calendar is even a little more regular next year, Mejias said, “that will make our lives easier.”

    This year, flu and RSV have also exploited Americans’ higher-than-average vulnerability. Initial encounters with RSV in particular can be rough, especially in infants, whose airways are still tiny; the sickness tempers with age as the body develops and immunity builds, leaving most children well protected by toddlerhood. But this fall, the pool of undefended kids is larger than usual. Children born just before the pandemic, or during the phases of the crisis when mitigations aplenty were still in place, may be meeting influenza or RSV for the first time. And many of them were born to mothers who had themselves experienced fewer infections and thus passed fewer antibodies to their baby while pregnant or breastfeeding. Some of the consequences may already have unfurled elsewhere in the world: Australia’s most recent flu season hit kids hard and early, and Nicaragua’s wave at the start of 2022 infected children at rates “higher than what we saw during the 2009 pandemic,” says Aubree Gordon, an epidemiologist at the University of Michigan.

    Read: What a ‘tripledemic’ means for your body

    In the U.S., many hospitals are now admitting far more toddlers and older children for respiratory illnesses than they normally do, says Mari Nakamura, a pediatric-infectious-disease specialist at Boston Children’s Hospital. The problem is worsened by the fact that many adults and school-age kids avoided their usual brushes with flu and RSV while those viruses were in exile, making it easier for the pathogens to spread once crowds flocked back together. “I wouldn’t be surprised,” Gordon told me, “if we see 50 to 60 percent of kids get infected with flu this year”—double the estimated typical rate of 20 to 30 percent. Caregivers too are falling sick; when I called Edwards, I could hear her husband and grandson coughing in the background.

    By next year, more people’s bodies should be clued back in to the season’s circulating strains, says Helen Chu, a physician and an epidemiologist at the University of Washington. Experts are also hopeful that the toolkit for fighting RSV will soon be much improved. Right now, there are no vaccines for the virus, and only one preventive drug is available in the U.S.: a tough-to-administer monoclonal antibody that’s available only to high-risk kids. But at least one RSV vaccine and another, less cumbersome antibody therapy (already being used in Europe) are expected to have the FDA’s green light by next fall.

    Even with the addition of better tech, though, falls and winters may be grueling for many years to come. SARS-CoV-2 is here to stay, and it will likely compound the respiratory burden by infecting people on its own or raising the risk of co-infections that can worsen and prolong disease. Even nonoverlapping illnesses might cause issues if they manifest in rapid sequence: Very serious bouts of COVID, for instance, can batter the respiratory tract, making it easier for other microbes to colonize.

    A few experts have begun to wonder if even milder tussles with SARS-CoV-2 might leave people more susceptible to other infections in the short or long term. Given the coronavirus’s widespread effects on the body, “we can’t be cavalier” about that possibility, says Flor Muñoz Rivas, a pediatrician at Baylor College of Medicine. Mejias and Octavio Ramilo, also at Nationwide, recently found that among a small group of infants, those with recent SARS-CoV-2 infections seemed to have a rougher go with a subsequent bout of RSV. The trend needs more study, though; it’s not clear which kids might be at higher risk, and Mejias doubts that the effect would last more than a few months.

    Gordon points out that some people may actually benefit from the opposite scenario: A recent brush with SARS-CoV-2 could bolster the body’s immune defenses against a second respiratory invader for a few days or weeks. This phenomenon, called viral interference, wouldn’t halt an outbreak by itself, but it’s thought to be part of the reason waves of respiratory disease don’t usually spike simultaneously: The presence of one microbe can sometimes crowd others out. Some experts think last year’s record-breaking Omicron spike helped punt a would-be winter flu epidemic to the spring.

    Even if all of these variables were better understood, the vagaries of viral evolution could introduce a plot twist. A new variant of SARS-CoV-2 may yet emerge; a novel strain of flu could cause a pandemic of its own. RSV, for its part, is not thought to be as quick to shape-shift, but the virus’s genetics are not well studied. Mejias and Ramilo’s data suggest that the arrival of a gnarly RSV strain in 2019 may have pushed local hospitalizations past their usual highs.

    Read: Will we get Omicron’d again?

    Behavioral and infrastructural factors could cloud the forecast as well. Health-care workers vacated their posts in droves during the pandemic, and many hospitals’ pediatric-bed capacity has shrunk, leaving supply grossly inadequate to address current demand. COVID-vaccination rates in little kids also remain abysmal, and many pediatricians are worried that anti-vaccine sentiment could stymie the delivery of other routine immunizations, including those against flu. Even temporary delays in vaccination can have an effect: Muñoz Rivas points out that the flu’s early arrival this year, ahead of when many people signed up for their shot, may now be aiding the virus’s spread. The new treatments and vaccines for RSV “could really, really help,” Nakamura told me, but “only if we use them.”

    Next fall comes with few guarantees: The seasonal schedule may not rectify itself; viruses may not give us an evolutionary pass. Our immune system will likely be better-prepared to fend off flu, RSV, rhinovirus, enterovirus, and more—but that may not be enough on its own. What we can control, though, is how we choose to arm ourselves. The past few years proved that the world does know how to drive down rates of respiratory disease. “We had so little contagion during the time we were trying to keep COVID at bay,” Edwards told me. “Is there something to be learned?”

    Katherine J. Wu

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  • Will We Get Omicron’d Again?

    Will We Get Omicron’d Again?

    In COVID terms, the middle of last autumn looked a lot like this one. After a rough summer, SARS-CoV-2 infections were down; hospitalizations and deaths were in a relative trough. Kids and workers were back in schools and offices, and another round of COVID shots was rolling out. Things weren’t great … but they weren’t the most terrible they’d ever been. There were vaccines; there were tests; there were drugs. The worst winter development the virus might produce, some experts thought, might involve the spawning of some nasty Delta offshoot.

    Then, one year ago this week, Omicron appeared. The first documented infection with the variant was identified from a specimen collected in South Africa on November 9, 2021; by December 1, public-health officials had detected cases in countries all around the globe, including the United States. Twenty days later, Omicron had unseated Delta as America’s dominant SARS-CoV-2 morph. The new, highly mutated variant could infect just about anyone it encountered—even if they’d already caught a previous version of the virus or gotten several shots of a vaccine. At the beginning of December, and nearly two years into the pandemic, researchers estimated that roughly one-third of Americans had contracted SARS-CoV-2. By the middle of February this year, that proportion had nearly doubled.

    Omicron’s arrival and rapid spread around the world was, and remains, this crisis’s largest inflection point to date. The variant upended scientists’ expectations about SARS-CoV-2’s evolution; it turned having COVID into a horrific norm. Now, as the U.S. approaches its Omicronniversary, conditions may seem ripe for an encore. Some experts worry that the emergence of another Greek-letter variant is overdue. “I’m at a loss as to why we haven’t seen Pi yet,” says Salim Abdool Karim, an epidemiologist at the Centre for the AIDS Programme of Research in South Africa. “I think there’s a chance we still will.”

    A repeat of last winter seems pretty unlikely, experts told me. But with a virus this unpredictable, there’s no guarantee that we won’t see disaster unspool again.

    Read: The worst pediatric care crisis in decades

    A lot has changed since last year. For one thing, population immunity to SARS-CoV-2 is higher. Far more people have received additional doses of vaccine, many of them quite recently, with an updated formula that’s better tailored to the variants du jour. Plus, at this point, nearly every American has been infected at least once—and most of them with at least some subvariant of Omicron, says Shaun Truelove, an epidemiologist and a modeler at Johns Hopkins University. These multiple layers of protection make it more challenging for the average SARS-CoV-2 spin-off to severely sicken people. They also raise transmission obstacles for the coronavirus in whatever form it takes.

    Omicron does seem to have ushered in “a different phase of the pandemic,” says Verity Hill, an evolutionary virologist at Yale. The variants that took over different parts of the world in 2021 rose in a rapid succession of monarchies: Alpha, Beta, Gamma, Delta. But in the U.S. and elsewhere, 2022 has so far been an oligarchy of Omicron offshoots. Perhaps the members of the Omicron lineage are already so good at moving among hosts that the virus hasn’t needed a major upgrade since.

    If that’s the case, SARS-CoV-2 may end up a victim of its own success. The Omicron subvariants BQ.1 and BQ1.1 appear capable of spreading up to twice as fast as BA.5, according to laboratory data. But their takeover in the U.S. has been slow and halting, perhaps because they’re slogging through a morass of immunity to the Omicron family. That alone makes it less likely that any single Omicron subvariant will re-create the sudden surge of late 2021 anytime soon. In South Africa and the United Kingdom, for instance, different iterations of Omicron seem to have triggered just modest bumps in sickness in recent months. (That said, those countries—with their distinct demographics and vaccination and infection histories—aren’t a perfect bellwether for the U.S.)

    For an Omicron 2021 redux to happen, SARS-CoV-2 might need to undergo a substantial genetic makeover—which Abdool Karim thinks would be very difficult for the virus to manage. In theory, there are only so many ways that SARS-CoV-2 can scramble its appearance while retaining its ability to latch onto our cells; by now, its options should be somewhat slimmed. And the longer the Omicron line of succession persists, the tougher it may be to upend. “It’s just getting harder to compete,” Hill told me.

    But the world has gotten overconfident before. Even if SARS-CoV-2 doesn’t produce a brand-new version of itself, low uptake of the bivalent vaccine could allow our defenses to wither, driving a surge all the same, Truelove told me. Our transmission-dampening behaviors too are slacker than they’ve been since the pandemic’s start. This time last year, 50 to 60 percent of Americans were regularly wearing masks. The latest figures, many of them several months old, are closer to 30 percent. “The more opportunities you give the virus to get into somebody,” Hill said, “the more chances you give it to get the group of mutations that could help it take off.” Immunocompromised people who remain chronically infected with older variants, such as Alpha or Delta, could also become the sites of new viral offshoots. (That may be how the world got Omicron to begin with.)

    Going on probability alone, “it seems more likely that we’ll keep going with these subvariants of Omicron rather than dealing with something wholly brand-new,” says Maia Majumder, an epidemiologist at Boston Children’s Hospital. But Lauren Ancel Meyers, an infectious-disease modeler at the University of Texas at Austin, warns that plenty of uncertainty remains. “What we don’t have is a really data-driven model right now that tells us if, when, where, and what kind of variants will be emerging in the coming months and years,” she told me. Our window into the future is only getting foggier too as fewer people submit their test results—or take any test at all—and surveillance systems continue to go offline.

    It wouldn’t take another Omicron-type event to hurl us into disarray. Maybe none of the Omicron subvariants currently jockeying for control will surge ahead of the pack. But several of them might yet drive regional epidemics, Majumder told me, depending on the local nitty-gritty of who’s susceptible to what. And as winter looms, some of the biggest holes in our COVID shield remain unpatched. People who are immunocompromised are losing their last monoclonal-antibody treatments, and although powerful drugs exist to slash the risk of severe disease and death, useful preventives and treatments for long COVID remain sparse.

    Read: The end of Evusheld

    Our nation’s capacity to handle new COVID cases is also low, Majumder said. Already, hospitals around the country are being inundated with other respiratory viruses—RSV, flu, rhinovirus, enterovirus—all while COVID is still kicking in the background. “If flu has taken over hospital beds,” says Srini Venkatramanan, an infectious-disease modeler at the University of Virginia, even a low-key wave will “feel like it’s having a much bigger impact.”

    As the country approaches its second holiday season with Omicron on deck, this version of the virus may “feel familiar,” Majumder pointed out. “I think people perceive the current circumstances to be safer than they were last year,” she said—and certainly, some of them are. But the fact that Omicron has lingered is not entirely a comfort. It is also, in its way, a reminder of how bad things once were, and how bad they could still get.

    Katherine J. Wu

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  • The Worst Pediatric-Care Crisis in Decades

    The Worst Pediatric-Care Crisis in Decades

    At the height of the coronavirus pandemic, as lines of ambulances roared down the streets and freezer vans packed into parking lots, the pediatric emergency department at Our Lady of the Lake Children’s Hospital, in Baton Rouge, Louisiana, was quiet.

    It was an eerie juxtaposition, says Chris Woodward, a pediatric-emergency-medicine specialist at the hospital, given what was happening just a few doors down. While adult emergency departments were being inundated, his team was so low on work that he worried positions might be cut. A small proportion of kids were getting very sick with COVID-19—some still are—but most weren’t. And due to school closures and scrupulous hygiene, they weren’t really catching other infections—flu, RSV, and the like—that might have sent them to the hospital in pre-pandemic years. Woodward and his colleagues couldn’t help but wonder if the brunt of the crisis had skipped them by. “It was, like, the least patients I saw in my career,” he told me.

    That is no longer the case.

    Across the country, children have for weeks been slammed with a massive, early wave of viral infections—driven largely by RSV, but also flu, rhinovirus, enterovirus, and SARS-CoV-2. Many emergency departments and intensive-care units are now at or past capacity, and resorting to extreme measures. At Johns Hopkins Children’s Center, in Maryland, staff has pitched a tent outside the emergency department to accommodate overflow; Connecticut Children’s Hospital mulled calling in the National Guard. It’s already the largest surge of infectious illnesses that some pediatricians have seen in their decades-long careers, and many worry that the worst is yet to come. “It is a crisis,” Sapna Kudchadkar, a pediatric-intensive-care specialist and anesthesiologist at Johns Hopkins, told me. “It’s bananas; it’s been full to the gills since September,” says Melissa J. Sacco, a pediatric-intensive-care specialist at UVA Health. “Every night I turn away a patient, or tell the emergency department they have to have a PICU-level kid there for the foreseeable future.”

    I asked Chris Carroll, a pediatric-intensive-care specialist at Connecticut Children’s, how bad things were on a scale of 1 to 10. “Can I use a Spinal Tap reference?” he asked me back. “This is our 2020. This is as bad as it gets.”

    Read: The strongest signal that Americans should worry about flu this winter

    The autumn crush, experts told me, is fueled by dual factors: the disappearance of COVID mitigations and low population immunity. For much of the pandemic, some combination of masking, distancing, remote learning, and other tactics tamped down on the transmission of nearly all the respiratory viruses that normally come knocking during the colder months. This fall, though, as kids have flocked back into day cares and classrooms with almost no precautions in place, those microbes have made a catastrophic comeback. Rhinovirus and enterovirus were two of the first to overrun hospitals late this summer; now they’re being joined by RSV, all while SARS-CoV-2 remains in play. Also on the horizon is flu, which has begun to pick up in the South and the mid-Atlantic, triggering school closures or switches to remote learning. During the summer of 2021, when Delta swept across the nation, “we thought that was busy,” Woodward said. “We were wrong.”

    Children, on the whole, are more susceptible to these microbes than they have been in years. Infants already have a rough time with viruses like RSV: The virus infiltrates the airways, causing them to swell and flood with mucus that their tiny lungs may struggle to expel. “It’s almost like breathing through a straw,” says Marietta Vazquez, a pediatric-infectious-disease specialist at Yale. The more narrow and clogged the tubes get, “the less room you have to move air in and out.” Immunity accumulated from prior exposures can blunt that severity. But with the pandemic’s great viral vanishing, kids missed out on early encounters that would have trained up their bodies’ defensive cavalry. Hospitals are now caring for their usual RSV cohort—infants—as well as toddlers, many of whom are sicker than expected. Infections that might, in other years, have produced a trifling cold are progressing to pneumonia severe enough to require respiratory support. “The kids are just not handling it well,” says Stacy Williams, a PICU nurse at UVA Health.

    Coinfections, too, have always posed a threat—but they’ve grown more common with SARS-CoV-2 in the mix. “There’s just one more virus they’re susceptible to,” Vazquez told me. Each additional bug can burden a child “with a bigger hill to climb, in terms of recovery,” says Shelby Lighton, a nurse at UVA Health. Some patients are leaving the hospital healthy, only to come right back. There are kids who “have had four respiratory viral illnesses since the start of September,” Woodward told me.

    Pediatric care capacity in many parts of the country actually shrank after COVID hit, Sallie Permar, a pediatrician at NewYork-Presbyterian and Weill Cornell Medicine, whose hospital was among those that cut beds from its PICU, told me. A mass exodus of health-care workers—nurses in particular—has also left the system ill-equipped to meet the fresh wave of demand. At UVA Health, the pediatric ICU is operating with maybe two-thirds of the core staff it needs, Williams said. Many hospitals have been trying to call in reinforcements from inside and outside their institutions. But “you can’t just train a bunch of people quickly to take care of a two-month-old,” Kudchadkar said. To make do, some hospitals are doubling up patients in rooms; others have diverted parts of other care units to pediatrics, or are sending specialists across buildings to stabilize children who can’t get a bed in the ICU. In Baton Rouge, Woodward is regularly visiting the patients who have just been admitted to the hospital and are still being held in the emergency department, trying to figure out who’s healthy enough to go home so more space can be cleared. His emergency department used to take in, on average, about 130 patients a day; lately, that number has been closer to 250. “They can’t stay,” he told me. “We need this room for somebody else.”

    Experts are also grappling with how to strike the right balance between raising awareness among caregivers and managing fears that may morph into overconcern. On the one hand, with all the talk of SARS-CoV-2 being “mild” in kids, some parents might ignore the signs of RSV, which can initially resemble those of COVID, then get much more serious, says Ashley Joffrion, a respiratory therapist at Baton Rouge General Medical Center. On the other hand, if families swamp already overstretched hospitals with illnesses that are truly mild enough to resolve at home, the system could fracture even further. “We definitely don’t want parents bringing kids in for every cold,” Williams told me. The key signs of severe respiratory sickness in children include wheezing, grunting, rapid or labored breaths, trouble drinking or swallowing, and bluing of the lips or fingernails. When in doubt, experts told me, parents should call their pediatrician for an assist.

    Read: The great pandemic hand-washing blooper

    With winter still ahead, the situation could take an even darker turn, especially as flu rates climb, and new SARS-CoV-2 subvariants loom. In most years, the chilly viral churn doesn’t abate until late winter, which means hospitals may be only at the start of a grueling few months. And still-spotty uptake of COVID vaccines among little kids, coupled with a recent dip in flu-shot uptake and the widespread abandonment of infection-prevention measures, could make things even worse, says Abdallah Dalabih, a pediatric-intensive-care specialist at Arkansas Children’s.

    The spike in respiratory illness marks a jarring departure from a comforting narrative that’s dominated the intersection of infectious disease and little children’s health for nearly three years. When it comes to respiratory viruses, little children have always been a vulnerable group. This fall may force Americans to reset their expectations around young people’s resilience and recall, Lighton told me, “just how bad a ‘common cold’ can get.”

    Katherine J. Wu

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  • COVID Antibody Treatments Are in Decline

    COVID Antibody Treatments Are in Decline

    For the first couple of years of the coronavirus pandemic, the crisis was marked by a succession of variants that pummeled us one at a time. The original virus rapidly gave way to D614G, before ceding the stage to Alpha, Delta, Omicron, and then Omicron’s many offshoots. But as our next COVID winter looms, it seems that SARS-CoV-2 may be swapping its lead-antagonist approach for an ensemble cast: Several subvariants are now vying for top billing.

    In the United States, BA.5—dominant since the end of spring—is slowly yielding to a slew of its siblings, among them BA.4.6, BF.7, BQ.1, and BQ.1.1; another subvariant, XBB, threatens to steal the spotlight from overseas. Whether all of these will divvy up infections in the next few months, or whether they’ll be pushed aside by something new, is still anyone’s guess. Either way, the forecast looks a little grim. None of the new variants will completely circumvent the full set of immune defenses that human bodies, schooled by vaccines or past infections, can launch. Yet all of them seem pretty good at dodging a hefty subset of our existing antibodies.

    For anyone who gets infected, such evasions could make the difference between asymptomatic and feeling pretty terrible. And for the subset of people who become sick enough to need clinical care, the consequences could get even worse. Some of our best COVID treatments are made from single antibodies tailored to the virus, which may simply cease to work as SARS-CoV-2 switches up its form. Past variants have already knocked out three such concoctions—REGEN-COV, sotrovimab, and bamlanivimab/etesevimab—from the U.S. arsenal. The only two left are bebtelovimab, a treatment for people who have already been infected, and Evusheld, a crucial supplement to vaccination for those who are moderately or severely immunocompromised; both are still deployed in hospitals countrywide. But should another swarm of variants take over, these two lone antibody therapies could also be obsolete within months, if not weeks. “It seems like the writing is on the wall,” says Erin McCreary, an infectious-disease pharmacist at the University of Pittsburgh Medical Center. “I live constantly low-key worried that I’m not going to have an active therapy for my patients, and I won’t be able to help them.”

    All of this bodes poorly for this winter and beyond. In the near term, millions of immunocompromised people could be left without viable options either to keep SARS-CoV-2 at bay or to temper its blaze once an infection begins to burn. And that loss would set a troubling precedent for seasons to come. The business end of the virus “is now adapting so rapidly that I don’t know how it’s going to be possible for monoclonals to keep up,” says Jeanne Marrazzo, an infectious-disease physician at the University of Alabama at Birmingham. Experts may need to revamp the strategies they use to bring new therapies to market—or find themselves, once again, in a serious bind. “I worry,” Marrazzo told me, “that we’re on a razor’s edge.”

    Whatever happens this winter, doctors will still have some options to treat COVID patients. Experts don’t think the virus will develop widespread resistance to our antiviral drugs—molnupiravir, remdesivir, and Paxlovid—“anytime soon,” Marrazzo said. But the vanishing of effective antibody therapies would still leave a massive hole that other treatments can’t fill. The benefits of molnupiravir seem lackluster at best; remdesivir offers a few more perks but is a hassle to administer, requiring several days of infusions. And although Paxlovid has worked wonders for people in high-risk groups, one of its ingredients can screw with a long list of other drugs. McCreary has seen many patients hospitalized, she told me, because their physicians prescribed Paxlovid without properly adjusting their regular meds. “Plus,” she added, “Paxlovid tastes awful.”

    Read: Paxlovid mouth is real—and gross

    Monoclonal antibodies aren’t perfect. But at their best, they’re astoundingly effective and safe, and often the first thing McCreary reaches for when caring for newly infected people. Some patients are also “just more comfortable with monoclonal antibodies than they are with antivirals,” says Mari Nakamura, an infectious-disease specialist at Boston Children’s Hospital. And Evusheld remains the only COVID treatment that is authorized to guard people before they encounter the virus at all. People who don’t mount much of a response to vaccines can sign up for a pair of injections—one into each gluteal muscle—and expect to have their defenses buoyed for a good six months. “I see it as an extension of vaccines for those who are vulnerable,” says Jonathan Abraham, an immunologist and physician at Harvard Medical School.

    The greatest strength of these treatments, however, also happens to be their most glaring weakness. Monoclonal antibodies work their magic by glomming so tightly onto SARS-CoV-2’s surface that the virus can’t dock onto our cells. Their grip is ultra precise—enough so that it can be nullified by just one viral mutation in exactly the right spot. Those genetic changes have already booted antibody treatments from our lineup. Now the data hint that bebtelovimab might not work against BQ.1 or BQ1.1. The list of subvariants that might be able to resist Evusheld is even longer: BQ.1, BQ.1.1, BA.4.6, BA.2.75.2, BF.7, and XBB.

    Soon health-care providers will have to start making tough calls about when to retire these two antibody treatments—and with few hard rules to guide them. Resistance can be a pretty murky concept: Viral mutations sometimes soften an antibody’s grasp without totally obliterating it. With antibiotics, for example, doctors can respond to some forms of low-level drug resistance just by increasing the dose, McCreary told me. But COVID monoclonal antibodies are still new to the scene. Even when an antibody cocktail has clearly become functionally useless against a given set of variants, there’s no universal standard for deciding when those variants have become so common that the cocktail should be shelved. (When I asked the FDA about this, it declined to comment on specifics.) So the choice is often left up to individual hospitals, Nakamura told me, which can create a bit of a patchwork in how experts are approaching COVID treatment—and put a burden on surveillance efforts to deliver hyperlocal data in real time.

    In Pittsburgh, McCreary’s team has, in prior seasons, pulled monoclonals when they stop working against just 20 to 30 percent of the reported variant milieu. Alpana Waghmare, a physician at the Fred Hutchinson Cancer Center and Seattle Children’s Hospital, told me her threshold may be closer to about 50 percent, though she pointed out that the more the options dwindle, the more willing health-care workers may be to keep using a variant-mismatched antibody. Alfred Kim, a rheumatologist at Washington University in St. Louis, told me he’d need to see resistant variants make up “the majority in a region” before he’d even consider putting an antibody out to pasture. There’s little downside to administering the treatments, he said, and for his patients, the potential cost of withholding them is just too immense.

    Should bebtelovimab and Evusheld be forced from the stage in the coming months, they might, at least, have a few understudies waiting in the wings. Regeneron, the maker of the late REGEN-COV, has two antibody treatments in Phase 1 trials, according to a spokesperson; AstraZeneca, Evusheld’s parent, also has replacements in development, though a spokesperson declined to provide more details on where in the pipeline they sat. Eli Lilly, which manufactures bebtelovimab and the now-gone bamlanivimab/etesevimab, didn’t respond to my questions about whether they were cooking up new recipes for future use. Vir, which makes sotrovimab—still available overseas—is working on “several highly potent” new antibodies “that have shown activity against all COVID-19 variants tested to date including BQ1.1,” according to a spokesperson.

    Clearing drugs for human use remains a plodding process; all of those options could be months away from regular use. “The virus may have moved on” by then, Abraham told me. Already, experts are grappling with whether once-a-year shots will be enough to keep pace with coronavirus evolution; updates on the treatment side may have to come much faster. The problem could get worse as SARS-CoV-2 lineages continue to jockey for control. For the moment, at least, the leading variants are invalidating antibody treatments in relatively similar ways. But if variants diverge further, pharmaceutical companies could have an even tougher time devising broadly effective antibody therapies.

    Some experts are also concerned that the market for monoclonals may be going dry. Antibodies are expensive to produce, and with a turnover rate this high, the industry may not have much incentive to stay involved, McCreary told me. Marrazzo, too, thinks the urgency may have lessened with the advent of oral antivirals, and the rush to return to “normal.” If anything, though, the need for good monoclonal options may be growing in urgency. Treatments such as REGEN-COV and bamlanivimab/etesevimab once had clearance to be used in people right after they were exposed to SARS-CoV-2—a sort of emergency antiviral contraceptive. Now no monoclonals are available for so-called postexposure prophylactic use. Kids, too, could use more treatment options. Children under 12 are eligible for three-day courses of remdesivir, given by IV infusion—but those are a tough ask for many families who don’t have the time or means to make such frequent trips to the hospital, Nakamura told me. “And that’s pretty much it.”

    Yet no one would feel the loss of antibody-based COVID treatments more than the immunocompromised, Waghmare told me. “It’s this horrible nexus,” Marrazzo said: The most vulnerable people will lose their best options first. Many of those who received Evusheld in the spring will soon be due for their second set of injections, scheduled six months after the first. As of right now, “we’re still telling patients to come in,” McCreary told me. But that may not be the advice she gives next month, or the next. Robyn Ruth, of Augusta County, Virginia, is at that decision point now. Her first experience with the treatment, in April, was momentous: “I had my first hug since the beginning of the pandemic,” Ruth told me. “I just remember my knees buckled, because I hadn’t touched another human being in so long.” In the weeks after, Ruth felt safe enough to go to a couple of doctor appointments and visit a few friends, even garden in their company—activities she hadn’t engaged in since the start of 2020. But as variants continue to chip away at Evusheld’s efficacy, Ruth is steeling herself for the possibility that another dose won’t bring the same relief.

    Caregivers and patients alike must now strategize for what could be a very difficult winter stretch. Many immunocompromised people can still benefit from vaccines, even if not as much as others. Marrazzo also cautiously pointed out that if things get bad enough, some providers might go back to convalescent plasma—a treatment with just so-so effectiveness that’s hard to roll out in large quantities, and that doesn’t deliver consistent results—as a desperate stopgap. Other than that, though, it’ll come down to the behavioral measures that many Americans have long since abandoned: isolation, quarantine, masking, distancing.

    Read: It’s gotten awkward to wear a mask

    Nakamura told me she’s been struggling to deliver optimistic advice. “All they can do is try not to get the virus,” she said. She also worries about what might happen should her young patients actually fall ill. “Our hospitals are already overflowing,” she said, amid an early seasonal surge of respiratory viruses, including RSV, and a massive mental-health crisis. McCreary, too, knows many tough conversations are ahead. “There’s nothing worse than one day having something safe and highly effective,” she told me, “and the next day, it’s, ‘Sorry, we don’t have that anymore.’”

    For some, the simultaneous disappearance of bebtelovimab and Evusheld could almost rewind the clock to the pandemic’s start. Sara Anne Willette, a data analyst in Ames, Iowa, has a condition called common variable immunodeficiency that keeps her from making certain types of protective antibodies. She also has a history of anaphylaxis to antivirals, potentially making bebtelovimab her only postinfection treatment option should she fall ill. Willette’s second dose of Evusheld is scheduled for December, but she’s not sure whether, by that point, risking the trip will even be practical. “It feels like we’re back at square one,” she told me. “I get COVID, and it’s ‘go it alone.’”

    Katherine J. Wu

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  • Ringo Starr Has Covid-19 Rebound, Cancels 2022 Tour

    Ringo Starr Has Covid-19 Rebound, Cancels 2022 Tour

    You know it don’t come easy. That’s what legendary singer, songwriter, and drummer Ringo Starr first sang in 1971. It’s also what can often be said about having Covid-19, especially when you suffer a Covid-19 rebound, something that Starr apparently now is experiencing. And this rebound has prompted Starr to cancel the rest of his 2022 North American tour. That’s essentially what the rock super-Starr tweeted on October 13:

    Starr’s recent battle with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when he was diagnosed with Covid-19 sometime before an October 3 press release. That press release had indicated that Starr’s Covid-19 diagnosis would force him and his All Starr Band to cancel shows from October 2 through October 9. This included shows in the U.S. (Minnesota) and Canada (Manitoba, Saskatchewan, Alberta, and British Columbia.)

    Then seven days later, on October 10, Starr posted on Instagram that he’s “On the road again I will see you in Seattle on Tuesday the 11th Portland Wednesday I am negative peace and love everybody thanks for waiting Ringo [sic]” as you can see here:

    Presumably “negative peace” didn’t mean war but instead meant that he had tested negative for Covid-19 and would be having fans lend them his ears so that he could sing them a song in Seattle on October 11. But that resumption turned out to be short-lived as three days later instead of singing “Back Off Boogaloo,” the drumming Starr indicated on Twitter that he was back with Covid-19.

    The 82-year-old Starr, who first rose to prominence in the 1960’s as the drummer for a band that you may or may not have heard of called The Beatles, is at higher risk for more severe Covid-19 outcomes given his age. However, he has gotten at least the primary two-dose series of Covid-19 vaccines. That’s based on what he had told Patrick Ryan in a interview published in USA Today on March 17, 2021. Back then Starr had said, “I’ve got both jabs and I’m feeling groovy.” When Ryan had asked him about side effects from the vaccine, Starr had replied, “Bad arm for the first one. And then the second one, with the doctor telling you, “You may feel fluish.” Nothing! Nothing! I felt let down.” Star added the following as well: “It was difficult trying to sleep on that side, but by 5 o’clock (the next day), it had gone. So I got away lightly, thank you, Lord. I think that’s because of the broccoli.,” referring to his blueberries, broccoli, and other veggies and fruit diet. Yes, whenever anything good happens in life, it’s always because of the broccoli, right.

    That was before recommendations for Covid-19 boosters had emerged. Having gotten vaccinated should offer him at least some protection against more severe Covid-19. But the level of protection will depend on how long ago his last Covid-19 vaccine dose was, no matter how much broccoli you eat.

    Staying up to date on Covid-19 vaccinations is important because, guess what, the Covid-19 pandemic ain’t over. It’s still going on, no matter what some political leaders may try to drum into your heads. And the concern right now is that yet another Covid-19 surge may right around the corner.

    Remember, while vaccination can offer you protection against more severe Covid-19, it’s not like being in a Yellow Submarine with the virus being outside. Vaccination won’t offer you 100% protection. With upswings in Covid-19 already occurring in Europe, you’ll need a little help from you friends in the coming months. It will help to not only maintain Covid-19 precautions such as wearing a face mask while indoors, maintaining appropriate levels of social distancing, and staying up-to-date on vaccination but also have others around you to do such things too. Recall all that “we’re all in this together” talk back in 2020? Well, it hasn’t become “every person for himself or herself” or “bleep everyone else.”

    Starr’s Covid-19 rebound also is a reminder that a negative Covid-19 test may not mean that you are done with Covid-19 after being infected with the SARS-CoV-2. False negatives can occur. Plus, by now, you’ve probably heard of quite a few Covid-19 rebound cases where people first test positive then test negative only to test positive again later. So even though it may not come easy to keep yourself isolated for a little longer (at least ten days) than is being recommended by some and confirming that you indeed are staying Covid-19 negative, doing so can be make sure that you aren’t giving the SARS-CoV-2 a tour around other people.

    Bruce Y. Lee, Senior Contributor

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