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Tag: severe disease

  • How Much Less to Worry About Long COVID Now

    How Much Less to Worry About Long COVID Now

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    Compared with the worst days of the pandemic—when vaccines and antivirals were nonexistent or scarce, when more than 10,000 people around the world were dying each day, when long COVID largely went unacknowledged even as countless people fell chronically ill—the prognosis for the average infection with this coronavirus has clearly improved.

    In the past four years, the likelihood of severe COVID has massively dropped. Even now, as the United States barrels through what may be its second-largest wave of SARS-CoV-2 infections, rates of death remain near their all-time low. And although tens of thousands of Americans are still being hospitalized with COVID each week, emergency rooms and intensive-care units are no longer routinely being forced into crisis mode. Long COVID, too, appears to be a less common outcome of new infections than it once was.

    Read: The future of long COVID

    But where the drop in severe-COVID incidence is clear and prominent, the drop in long-COVID cases is neither as certain nor as significant. Plenty of new cases of the chronic condition are still appearing with each passing wave—even as millions of people who developed it in years past continue to suffer its long-term effects.

    In a way, the shrinking of severe disease has made long COVID’s dangers more stark: Nowadays, “long COVID to me still feels like the biggest risk for most people,” Matt Durstenfeld, a cardiologist at UC San Francisco, told me—in part because it does not spare the young and healthy as readily as severe disease does. Acute disease, by definition, eventually comes to a close; as a chronic condition, long COVID means debilitation that, for many people, may never fully end. And that lingering burden, more than any other, may come to define what living with this virus long term will cost.

    Most of the experts I spoke with for this story do think that the average SARS-CoV-2 infection is less likely to unfurl into long COVID than it once was. Several studies and data sets support this idea; physicians running clinics told me that, anecdotally, they’re seeing that pattern play out among their patient rosters too. The number of referrals coming into Alexandra Yonts’s long-COVID clinic at Children’s National, in Washington, D.C., for instance, has been steadily dropping in the past year, and the waitlist to be seen has shortened. The situation is similar, other experts told me, among adult patients at Yale and UCSF. Lisa Sanders, an internal-medicine physician who runs a clinic at Yale, told me that more recent cases of long COVID appear to be less debilitating than ones that manifested in 2020. “People who got the earliest versions definitely got whacked the worst,” she said.

    That’s reflective of how our relationship to COVID has changed overall. In the same way that immunity can guard a body against COVID’s most severe, acute forms, it may also protect against certain kinds of long COVID. (Most experts consider long COVID to be an umbrella term for many related but separate syndromes.) Once wised up to a virus, our defenses become strong and fast-acting, more able to keep infection from spreading and lingering, as it might in some long-COVID cases. Courses of illness also tend to end more quickly, with less viral buildup, giving the immune system less time or reason to launch a campaign of friendly fire on other tissues, another potential trigger of chronic disease.

    In line with that logic, a glut of studies has shown that vaccination—especially recent and repeated vaccination—can reduce a person’s chances of developing long COVID. “There is near universal agreement on that,” Ziyad Al-Aly, an epidemiologist and a clinician at Washington University in St. Louis, told me. Some experts think that antiviral use may be making a dent as well, by decreasing the proportion of COVID cases that progress to severe disease, a risk factor for certain types of long COVID. Others have pointed to the possibility that more recent variants of the virus—some of them maybe less likely to penetrate deeply into the lungs or affect certain especially susceptible organs—may be less apt to trigger chronic illness too.

    But consensus on any of these points is lacking—especially on just how much, if at all, these interventions help. Experts are divided even on the effect of vaccines, which have the most evidence to back their protective punch: Some studies find that they trim risk by 15 percent, others up to about 70 percent. Paxlovid, too, has become a point of contention: While some analyses have shown that taking the antiviral early in infection helps prevent long COVID, others have found no effect at all. Any implication that we’ve tamed long COVID exaggerates how positive the overall picture is. Hannah Davis, one of the leaders of the Patient-Led Research Collaborative, who developed long COVID during the pandemic’s first months, told me that she’s seen how the most optimistic studies get the most attention from the media and the public. With a topic as unwieldy and challenging to understand as this, Davis said, “we still see overreactions to good news, and underreactions to bad news.”

    That findings are all over the place on long COVID isn’t a shock. The condition still lacks a universal definition or a standard method of diagnosis; when recruiting patients into their studies, research groups can rely on distinct sets of criteria, inevitably yielding disparate and seemingly contradictory sets of results. With vaccines, for instance, the more wide-ranging the set of potential long-COVID symptoms a study looks at, the less effective shots may appear—simply because “vaccines don’t work on everything,” Al-Aly told me.

    Studying long COVID has also gotten tougher. The less attention there is on COVID, “the less likely people are to associate long-term symptoms with it,” Priya Duggal, an infectious-disease epidemiologist at Johns Hopkins University, told me. Fewer people are testing for the virus. And some physicians still “don’t believe in long COVID—that’s what I hear a lot,” Sanders told me. The fact that fewer new long-COVID cases are appearing before researchers and clinicians could be in part driven by fewer diagnoses being made. Al-Aly worries that the situation could deteriorate further: Although long-COVID research is still chugging along, “momentum has stalled.” Others share his concern. Continued public disinterest, Duggal told me, could dissuade journals from publishing high-profile papers on the subject—or deter politicians from setting aside funds for future research.

    Even if new cases of long COVID are less likely nowadays, the incidence rates haven’t dropped to zero. And rates of recovery are slow, low, and still murky. At this point, “people are entering this category at a greater rate than people are exiting this category,” Michael Peluso, a long-COVID researcher at UCSF, told me. The CDC’s Household Pulse Survey, for instance, shows that the proportion of American adults reporting that they’re currently dealing with long COVID has held steady—about 5 to 6 percent—for more than a year (though the numbers have dropped since 2021). Long COVID remains one of the most debilitating chronic conditions in today’s world—and full recovery remains uncommon, especially, it seems, for those who have been dealing with the disease for the longest.

    Exact numbers on recovery are tricky to come by, for the same reasons that it’s difficult to pin down how effective preventives are. Some studies report rates far more optimistic than others. David Putrino, a physical therapist who runs a long-COVID clinic at Mount Sinai Health System, where he and his colleagues have seen more than 3,000 long-haulers since the pandemic’s start, told me his best estimates err on the side of the prognosis being poor. About 20 percent of Putrino’s patients fully recover within the first few months, he told me. Beyond that, though, he routinely encounters people who experience only partial symptom relief—as well as a cohort that, “no matter what we think to try,” Putrino told me, “we can’t even seem to stop them from deteriorating.” Reports of higher recovery rates, Putrino and other experts said, might be conflating improvement with a return to baseline, or mistakenly assuming that people who stop responding to follow-ups are better, rather than just done participating.

    Read: Long COVID is being erased—again

    Davis also worries that recovery rates could drop. Some researchers and clinicians have noticed that today’s new long-COVID patients are more likely than earlier patients to come in with certain neurological symptoms—among them, brain fog and dizziness—that have been linked to slower recovery trajectories, Lekshmi Santhosh, a pulmonary specialist at UCSF, told me.

    In any case, recovery rates are still modest enough that long-COVID clinics across the country—even ones that have noted a dip in demand—remain very full. Currently, Putrino’s clinic has a waitlist of three to six months. The same is true for clinical trials investigating potential treatments. One, run by Peluso, that is investigating monoclonal-antibody therapy has a waitlist that is “hundreds of people deep,” Peluso told me: “We do not have the problem of not being able to find people who want to participate.”

    Any decrease in long-COVID incidence may not last, either. Viral evolution could always produce a new variant or subvariant with higher risks of chronic issues. The protective effects of vaccination may also be quite temporary, and the fewer people who keep up to date with their shots, the more porous immunity’s safety net may become. In this way, kids—though seemingly less likely to develop long COVID overall—may remain worryingly vulnerable, Yonts told me, because they’re born entirely susceptible, and immunization rates in the youngest age groups remain extremely low. And yet, little kids who get long COVID may need to live with it the longest. Some of Yonts’s patients have barely started grade school and have already been sick for three-plus years—half of their lives so far, or more.

    Long COVID can also manifest after repeat infections of SARS-CoV-2—and although several experts told me they think that each subsequent exposure poses less incremental risk, any additional exposure is worrisome. People all over the world are being exposed, over and over again, as the pathogen spreads with blistering speed, more or less year-round, in populations that have mostly dropped mitigations and are mostly behind on annual shots (where they’re available). Additional infections can worsen the symptoms of people living with long COVID, or yank them out of remission. Long COVID’s inequities may also widen as marginalized populations, less likely to receive vaccines or antivirals and more likely to be exposed to the virus, continue to develop the condition at higher rates.

    There’s no question that COVID-19 has changed. The disease is more familiar; the threat of severe disease, although certainly not vanished, is quantitatively less now. But dismissing the dangers of the virus would be a mistake. Even if rates of new long-COVID cases continue to drop for some time, Yonts pointed out, they will likely stabilize somewhere. These risks will continue to haunt us and incur costs that will keep adding up. Long COVID may not kill as directly as severe, acute COVID has. But people’s lives still depend on avoiding it, Putrino told me—“at least, their life as they know it right now.”

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    Katherine J. Wu

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  • What Should Go Into This Year’s COVID Vaccine?

    What Should Go Into This Year’s COVID Vaccine?

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    This fall, millions of Americans might be lining up for yet another kind of COVID vaccine:  their first-ever dose that lacks the strain that ignited the pandemic more than three and a half years ago. Unlike the current, bivalent vaccine, which guards against two variants at once, the next one could, like the first version of the shot, have only one main ingredient—the spike protein of the XBB.1 lineage of the Omicron variant, the globe’s current dominant clade.

    That plan isn’t yet set. The FDA still has to convene a panel of experts, then is expected to make a final call on autumn’s recipe next month. But several experts told me they hope the agency follows the recent recommendation of a World Health Organization advisory group and focuses the next vaccine only on the strains now circulating.

    The switch in strategy—from two variants to one, from original SARS-CoV-2 plus Omicron to XBB.1 alone—would be momentous but wise, experts told me, reflecting the world’s updated understanding of the virus’s evolution and the immune system’s quirks. “It just makes a lot of sense,” said Melanie Ott, the director of the Gladstone Institute of Virology, in San Francisco. XBB.1 is the main coronavirus group circulating today; neither the original variant nor BA.5, the two coronavirus flavors in the bivalent shot, is meaningfully around anymore. And an XBB.1-focused vaccine may give the global population a particularly good shot at broadening immunity.

    At the same time, COVID vaccines are still in a sort of beta-testing stage. In the past three-plus years, the virus has spawned countless iterations, many of which have been extremely good at outsmarting us; we humans, meanwhile, are only on our third-ish attempt at designing a vaccine that can keep pace with the pathogen’s evolutionary sprints. And we’re very much still learning about the coronavirus’s capacity for flexibility and change, says Rafi Ahmed, an immunologist at Emory University. By now, it’s long been clear that vaccines are essential for preventing severe disease and death, and that some cadence of boosting is probably necessary to keep the shots’ effectiveness high. But when the virus alters its evolutionary tactics, our vaccination strategy must follow—and experts are still puzzling out how to account for those changes as they select the shots for each year.

    In the spring and summer of 2022, the last time the U.S. was mulling on a new vaccine formula, Omicron was still relatively new, and the coronavirus’s evolution seemed very much in flux. The pathogen had spent more than two years erratically slingshotting out Greek-letter variants without an obvious succession plan. Instead of accumulating genetic changes within a single lineage—a more iterative form of evolution, roughly akin to what flu strains do—the coronavirus produced a bunch of distantly related variants that jockeyed for control. Delta was not a direct descendant of Alpha; Omicron was not a Delta offshoot; no one could say with any certainty what would arise next, or when. “We didn’t understand the trajectory,” says Kanta Subbarao, the head of the WHO advisory group convened to make recommendations on COVID vaccines.

    And so the experts played it safe. Including an Omicron variant in the shot felt essential, because of how much the virus had changed. But going all in on Omicron seemed too risky—some experts worried that “the virus would flip back,” Subbarao told me, to a variant more similar to Alpha or Delta or something else. As a compromise, several countries, including the United States, went with a combination: half original, half Omicron, in an attempt to reinvigorate OG immunity while laying down new defenses against the circulating strains du jour.

    And those shots did bolster preexisting immunity, as boosters should. But they didn’t rouse a fresh set of responses against Omicron to the degree that some experts had hoped they would, Ott told me. Already trained on the ancestral version of the virus, people’s bodies seemed to have gotten a bit myopic—repeatedly reawakening defenses against past variants, at the expense of new ones that might have more potently attacked Omicron. The outcome was never thought to be damaging, Subbarao told me: The bivalent, for instance, still broadened people’s immune responses against SARS-CoV-2 compared with, say, another dose of the original-recipe shot, and was effective at tamping down hospitalization rates. But Ahmed told me that, in retrospect, he thinks an Omicron-only boost might have further revved that already powerful effect.

    Going full bore on XBB.1 now could keep the world from falling into that same trap twice. People who get an updated shot with that strain alone would receive only the new, unfamiliar ingredient, allowing the immune system to focus on the fresh material and potentially break out of an ancestral-strain rut. XBB.1’s spike protein also would not be diluted with one from an older variant—a concern Ahmed has with the current bivalent shot. When researchers added Omicron to their vaccine recipes, they didn’t double the total amount of spike protein; they subbed out half of what was there before. That left vaccine recipients with just half the Omicron-focused mRNA they might have gotten had the shot been monovalent, and probably a more lackluster antibody response.

    Recent work from the lab of Vineet Menachery, a virologist at the University of Texas Medical Branch, suggests another reason the Omicron half of the shot didn’t pack enough of an immunizing punch. Subvariants from this lineage, including BA.5 and XBB.1, carry at least one mutation that makes their spike protein unstable—to the point where it seems less likely than other versions of the spike protein to stick around for long enough to sufficiently school immune cells. In a bivalent vaccine, in particular, the immune response could end up biased toward non-Omicron ingredients, exacerbating the tendencies of already immunized people to focus their energy on the ancestral strain. For the same reason, a monovalent XBB.1, too, might not deliver the anticipated immunizing dose, Menachery told me. But if people take it (still a big if), and hospitalizations remain low among those up-to-date on their shots, a once-a-year total-strain switch-out might be the choice for next year’s vaccine too.

    Dropping the ancestral strain from the vaccine isn’t without risk. The virus could still produce a variant totally different from XBB.1, though that does, at this point, seem unlikely. For a year and a half now, Omicron has endured, and it now has the longest tenure of a single Greek-letter variant since the pandemic’s start. Even the subvariants within the Omicron family seem to be sprouting off each other more predictably; after a long stint of inconsistency, the virus’s shape-shifting now seems “less jumpy,” says Leo Poon, a virologist at the University of Hong Kong. It may be a sign that humans and the virus have reached a détente now that the population is blanketed in a relatively stable layer of immunity. Plus, even if a stray Alpha or Delta descendant were to rise up, the world wouldn’t be caught entirely off guard: So many people have banked protection against those and other past variants that they’d probably still be well buffered against COVID’s worst acute outcomes. (That reassurance doesn’t hold, though, for people who still need primary-series shots, including the kids being born into the world every day. An XBB.1 boost might be a great option for people with preexisting immunity. But a bivalent that can offer more breadth might still be the more risk-averse choice for someone whose immunological slate is blank.)

    More vaccination-strategy shifts will undoubtedly come. SARS-CoV-2 is still new to us; so are our shots. But the virus’s evolution, as of late, has been getting a shade more flu-like, and its transmission patterns a touch more seasonal. Regulators in the U.S. have already announced that COVID vaccines will probably be offered each year in the fall—as annual flu shots are. The viruses aren’t at all the same. But as the years progress, the comparison between COVID and flu shots could get more apt still—if, say, the coronavirus also starts to produce multiple, genetically distinct strains that simultaneously circulate. In that case, vaccinating against multiple versions of the virus at once might be the most effective defense.

    Flu shots could be a useful template in another way: Although those shots have followed roughly the same guidelines for many years, with experts meeting twice a year to decide whether and how to update each autumn’s vaccine ingredients, they, too, have needed some flexibility. Until 2012, the vaccines were trivalent, containing ingredients that would immunize people against three separate strains at once; now many, including all of the U.S.’s, are quadrivalent—and soon, based on new evidence, researchers may push for those to return to a three-strain recipe. At the same time, flu and COVID vaccines share a major drawback. Our shots’ ingredients are still selected months ahead of when the injections actually reach us—leaving immune systems lagging behind a virus that has, in the interim, sprinted ahead. Until the world has something more universal, our vaccination strategies will have to be reactive, scrambling to play catch-up with these pathogens’ evolutionary whims.

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    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

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    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.

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    Katherine J. Wu

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  • Are Colds Really Worse, or Are We All Just Weak Babies Now?

    Are Colds Really Worse, or Are We All Just Weak Babies Now?

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    For the past few weeks, my daily existence has been scored by the melodies of late winter: the drip of melting ice, the soft rustling of freshly sprouted leaves—and, of course, the nonstop racket of sneezes and coughs.

    The lobby of my apartment building is alive with the sounds of sniffles and throats being cleared. Every time I walk down the street, I’m treated to the sight of watery eyes and red noses. Even my work Slack is rife with illness emoji, and the telltale pings of miserable colleagues asking each other why they feel like absolute garbage. “It’s not COVID,” they say. “I tested, like, a million times.” Something else, they insist, is making them feel like a stuffed and cooked goose.

    That something else might be the once-overlooked common cold. After three years of largely being punted out of the limelight, a glut of airway pathogens—among them, adenovirus, RSV, metapneumovirus, parainfluenza, common-cold coronaviruses, and rhinoviruses galore—are awfully common again. And they’re really laying some people out. The good news is that there’s no evidence that colds are actually, objectively worse now than they were before the pandemic started. The less-good news is that after years of respite from a bunch of viral nuisances, a lot of us have forgotten that colds can be a real drag.

    Read: The pandemic broke the flu … again

    Once upon a time—before 2020, to be precise—most of us were very, very used to colds. Every year, adults, on average, catch two to three of the more than 200 viral strains that are known to cause the illnesses; young kids may contract half a dozen or more as they toddle in and out of the germ incubators that we call “day cares” and “schools.” The sicknesses are especially common during the winter months, when many viruses thrive amid cooler temps, and people tend to flock indoors to exchange gifts and breath. When the pandemic began, masks and distancing drove several of those microbes into hiding—but as mitigations have eased in the time since, they’ve begun their slow creep back.

    For the majority of people, that’s not really a big deal. Common-cold symptoms tend to be pretty mild and usually resolve on their own after a few days of nuisance. The virus infiltrates the nose and throat, but isn’t able to do much damage and gets quickly swept out. Some people may not even notice they’re infected at all, or may mistake the illness for an allergy—snottiness, drippiness, and not much more. Most of us know the drill: “Sometimes, it’s just congestion for a few days and feeling a bit tired for a while, but otherwise you’ll be just fine,” says Emily Landon, an infectious-disease physician at the University of Chicago. As a culture, we’ve long been in the habit of dismissing these symptoms as just a cold, not enough of an inconvenience to skip work or school, or to put on a mask. (Spoiler: The experts I spoke with were adamant that we all really should be doing those things when we have a cold.)

    The general infectious-disease dogma has always been that colds are a big nothing, at least compared with the flu. But gentler than the flu is not saying much. The flu is a legitimately dangerous disease that hospitalizes hundreds of thousands of Americans each year, and, like COVID, can sometimes saddle people with long-term symptoms. Even if colds are generally less severe, people can end up totally clobbered by headaches, exhaustion, and a burning sore throat; their eyes will tear up; their sinuses will clog; they’ll wake up feeling like they’ve swallowed serrated razor blades, or like their heads have been pumped full of fast-hardening concrete. It’s also common for cold symptoms to stretch out beyond a week, occasionally even two; coughs, especially, can linger long after the runny nose and headache resolve. At their worst, colds can lead to serious complications, especially in the very young, very old, and immunocompromised. Sometimes, cold sufferers end up catching a bacterial infection on top of their viral disease, a one-two punch that can warrant a trip to the ER. “The fact of the matter is, it’s pretty miserable to have a cold,” Landon told me. “And that’s how it’s always been.”

    Read: Don’t worry, it’s not COVID

    As far as experts can tell, the average severity of cold symptoms hasn’t changed. “It’s about perception,” says Jasmine Marcelin, an infectious-disease physician at the University of Nebraska Medical Center. After skipping colds for several years, “experiencing them now feels worse than usual,” she told me. Frankly, this was sort of a problem even before COVID came onto the scene. “Every year, I have patients who call me with ‘the worst cold they’ve ever had,’” Landon told me. “And it’s basically the same thing they had last year.” Now, though, the catastrophizing might be even worse, especially since pandemic-brain started prompting people to scrutinize every sniffle and cough.

    There’s still a chance that some colds this season might be a shade more unpleasant than usual. Many people falling sick right now are just coming off of bouts with COVID, flu, or RSV, each of which infected Americans (especially kids) by the millions this past fall and winter. Their already damaged tissues may not fare as well against another onslaught from a cold-causing virus.

    It’s also possible that immunity, or lack thereof, could be playing a small role. Many people are now getting their first colds in three-plus years, which means population-level vulnerability might be higher than it normally is this time of year, speeding the rate at which viruses spread and potentially making some infections more gnarly than they’d otherwise be. But higher-than-usual susceptibility seems unlikely to be driving uglier symptoms en masse, says Roby Bhattacharyya, an infectious-disease physician and microbiologist at Massachusetts General Hospital. Not all cold-causing viruses leave behind good immunity—but many of those that do are thought to prompt the body to mount relatively durable defenses against truly severe infections, lasting several years or more.

    Plus, for a lot of viruses going around right now, the immunity question is largely moot, Landon told me. So many different pathogens cause colds that a recent exposure to one is unlikely to do much against the next. A person could catch half a dozen colds in a five-year time frame and not even encounter the same type of virus twice.

    Read: Maybe consider not kissing that baby

    It’s also worth noting that what some people are categorizing as the worst cold they’ve ever had might actually be a far more menacing virus, such as SARS-CoV-2 or a flu virus. At-home rapid tests for the coronavirus often churn out false-negative results in the early days of infection, even after symptoms start. And although the flu can sometimes be distinguished from a cold by its symptoms, they’re often pretty similar. The illnesses can only be definitively diagnosed with a test, which can be difficult to come by.

    The pandemic has steered our perception of illness into a false binary: Oh no, it’s COVID or Phew, it’s not. COVID is undoubtedly still more serious than a run-of-the-mill cold—more likely to spark severe disease or chronic, debilitating symptoms that can last months or years. But the range of severity between them overlaps more than the binary implies. Plus, Marcelin points out, what truly is “just” a cold for one person might be an awful, weeks-long slog for someone else, or worse—which is why, no matter what’s turning your face into a snot factory, it’s still important to keep your germs to yourself. The current outbreak of colds may not be any more severe than usual. But there’s no need to make it bigger than it needs to be.

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    Katherine J. Wu

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  • Should Everyone Be Masking Again?

    Should Everyone Be Masking Again?

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    Winter is here, and so, once more, are mask mandates. After last winter’s crushing Omicron spike, much of America did away with masking requirements. But with cases once again on the rise and other respiratory illnesses such as RSV and influenza wreaking havoc, some scattered institutions have begun reinstating them. On Monday, one of Iowa’s largest health systems reissued its mandate for staff. That same day, the Oakland, California, city council voted unanimously to again require people to mask up in government buildings. A New Jersey school district revived its own mandate, and the Philadelphia school district announced that it would temporarily do the same after winter break.

    The reinstated mandates are by no means widespread, and that seems unlikely to change any time soon. But as we trudge into yet another pandemic winter, they do raise some questions. What role should masking play in winters to come? Is every winter going to be like this? Should we now consider the holiday season … masking season?

    These questions don’t have simple answers. Regardless of what public-health research tells us we should do, we’ve clearly seen throughout the pandemic that limits exist to what Americans will do. Predictably, the few recent mandates have elicited a good deal of aggrievement and derision from the anti-masking set. But even many Americans who diligently masked earlier in the pandemic seem to have lost their appetite for this sort of intervention as the pandemic has eased. In its most recent national survey of health behavior, the COVID States Project found that only about a quarter of Americans still mask when they go out, down from more than 80 percent at its peak. Some steadfast maskers have started feeling awkward: “I have personally felt like I get weird looks now wearing a mask,” Saskia Popescu, an epidemiologist at George Mason University, told me.

    Even so, masking remains one of the best and least obtrusive infection-prevention measures we have at our disposal. We haven’t yet been slammed this winter by another Omicronlike variant, but the pandemic is still here. COVID cases, hospitalizations, and deaths are all rising nationally, possibly the signs of another wave. Kids have been hit especially hard by the unwelcome return of influenza, RSV, and other respiratory viruses. All of this is playing out against the backdrop of low COVID-19-booster uptake, leaving people more vulnerable to death and severe disease if they get infected.

    All of which is to say: If you’re only going to mask for a couple of months of the year, now is a good time. “Should people be masking? Absolutely yes, right now,” Seema Lakdawala, a flu-transmission expert at Emory University, told me. That doesn’t mean masking everywhere all the time. Lakdawala masks at the grocery store, at the office, and while using public transportation, but not when she goes out to dinner or attends parties. Those activities pose a risk of infection, but Lakdawala’s goal is to reduce her risk, not to minimize it at all costs. A strategy that prevents you from enjoying the things you love most is not sustainable.

    Both Lakdawala and Popescu were willing to go so far as to suggest that masking should indeed become a seasonal fixture—just like skiing and snowmen, only potentially lifesaving and politically radioactive. Even before the pandemic, influenza alone killed tens of thousands of Americans every year, and more masking, even if only in certain targeted settings, could go a long way toward reducing the toll. “If we could just say, Hey, from November to February, we should all just mask indoors,” Lakdawala said, that would do a lot of good. “The idea of the unknown and the perpetualness of two years of things coming on and off, and then the confusing CDC county-by-county guideline—it just sort of makes it harder for everybody than if we had a simple message.” Universal mandates or recommendations that people mask at small social gatherings are probably too much to ask, Lakdawala told me. Instead, she favors some limited, seasonal mandates, such as on public transportation or in schools dealing with viral surges.

    David Dowdy, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, is all for masking season, he told me, but he’d be more hesitant to resort to mandates. “It’s hard to impose mandates without a very strong public-health rationale,” he said, especially in our current, hyperpolarized climate. And although that rationale clearly existed for much of the past two crisis-ridden years, it’s less clear now. “COVID is no longer this public-health emergency, but it’s still killing thousands of people every week, hundreds a day … so it becomes a more challenging balancing act,” Dowdy said.

    Rather than requirements, he favors broad recommendations. The CDC, for instance, could suggest that during flu season, people should consider wearing masks in crowded indoor spaces, the same way it recommends that everyone old enough get a flu shot each year. (Although the agency has hardly updated its “Interim Guidance” on masks and the flu since 2004, Director Rochelle Walensky has encouraged people to mask up this winter.) Another strategy, Dowdy said, could be making masks more accessible to people, so that every time they enter a public indoor space, they have the option of grabbing an N95.

    The course of the pandemic has both demonstrated the efficacy of widespread masking and rendered that strategy so controversial in America as to be virtually impossible. The question now is how to negotiate those two realities. Whatever answer we come up with this year, the question will remain next year, and for years after that. The pandemic will fade, but the coronavirus, like the other surging viruses this winter, will continue to haunt us in one form or another. “These viruses are here,” Lakdawala said. “They’re not going anywhere.”

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    Jacob Stern

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  • Is COVID a Common Cold Yet?

    Is COVID a Common Cold Yet?

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    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.”

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    Katherine J. Wu

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  • China’s COVID Wave Is Coming

    China’s COVID Wave Is Coming

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    In China, a dam seems on the verge of breaking. Following a wave of protests, the government has begun to relax some of its most stringent zero-COVID protocols, and regional authorities have trimmed back a slew of requirements for mass testing, quarantine, and isolation. The rollbacks are coming as a relief for the many Chinese residents who have been clamoring for change. But they’re also swiftly tilting the nation toward a future that’s felt inevitable for nearly three years: a flood of infections—accompanied, perhaps, by an uncharted morass of disease and death. A rise in new cases has already begun to manifest in urban centers such as Chongqing, Beijing, and Guangzhou. Now experts are waiting to see just how serious China’s outbreak will be, and whether the country can cleanly extricate itself from the epidemic ahead.

    For now, the forecast “is full of ifs and buts and maybes,” says Salim Abdool Karim, an epidemiologist at the Centre for the AIDS Programme of Research in South Africa. Perhaps the worst can be averted if the government does more to vaccinate the vulnerable and prep hospitals for a protracted influx of COVID patients; and if the community at large reinvests in a subset of mitigation measures as cases rise. “There is still the possibility that they may muddle through it without a mass die-off,” says Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations. “But even the most smooth and orderly transition,” he told me, “will not prevent a surge of cases.”

    China represents, in many ways, SARS-CoV-2’s final frontier. With its under-vaccinated residents and sparse infection history, the nation harbors “a more susceptible population than really any other large population I can think of,” says Sarah Cobey, an computational epidemiologist at the University of Chicago. Soon, SARS-CoV-2 will infiltrate that group of hosts so thoroughly that it will be nearly impossible to purge again. “Eventually, just like everyone else on Earth, everyone in China should expect to be infected,” says Michael Worobey, an evolutionary virologist at the University of Arizona.

    Read: How many COVID deaths will Chinese protesters accept?

    Whatever happens, though, China’s coming wave won’t recapitulate the one that swept most of the world in early 2020. Though it’s hard to say which versions of the virus are circulating in the country, a smattering of reports confirm the likeliest scenario: BF.7 and other Omicron subvariants predominate. Several of these versions of the virus seem to be a bit less likely than their predecessors to trigger severe disease. That, combined with the relatively high proportion of residents—roughly 95 percent—who have received at least one dose of a COVID vaccine, might keep many people from falling dangerously ill. The latest figures out of China’s CDC marked some 90 percent of the country’s cases as asymptomatic. “That’s an enormous fraction” compared with what’s been documented elsewhere, says Ben Cowling, an epidemiologist at the University of Hong Kong.

    That percentage, however, is undoubtedly increased by the country’s ultra-rigorous testing practices, which have been catching silent cases that other places might miss. All of Omicron’s iterations also remain capable of triggering severe disease and long COVID. And there are still plenty of worrying omens that climbing cases could reach a horrific peak, sit on a prolonged plateau, or both.

    One of China’s biggest weak spots is its immunity, or lack thereof. Although more than 90 percent of all people in the country have received at least two COVID shots, those over the age of 80 were not prioritized in the country’s initial rollout, and their rate of dual-dose coverage hovers around just 66 percent. An even paltrier fraction of older people have received a third dose, which the World Health Organization recommends for better protection. Chinese officials have vowed to buoy those numbers in the weeks ahead. But vaccination sites have been tougher to access than testing sites, and with few freedoms offered to the immunized, “the incentive structure is not built,” says Xi Chen, a global-health expert at Yale. Some residents are also distrustful of COVID vaccines. Even some health-care workers are wary of delivering the shots, Chen told me, because they’re fearful of liability for side effects.

    Regardless of the progress China makes in plugging the holes in its immunity shield, COVID vaccines won’t prevent all infections. China’s shots, most of which are based on chemically inactivated particles of the 2020 version of SARS-CoV-2, seem to be less effective and less durable than mRNA recipes, especially against Omicron variants. And many of China’s residents received their third doses many months ago. That means even people who are currently counted as “boosted” aren’t as protected as they could be.

    All of this and more could position China to be worse off than other places—among them, Australia, New Zealand, and Singapore—that have navigated out of a zero-COVID state, says Caitlin Rivers, a senior scholar at the Johns Hopkins Center for Health Security. Australia, for instance, didn’t soften its mitigations until it had achieved high levels of vaccine coverage among older adults, Rivers told me. China has also clung to its zero-COVID philosophy far longer than any other nation, leaving itself to contend with variants that are better at spreading than those that came before. Other countries charted their own path out of their restrictions; China is being forced into an unplanned exit.

    What Hong Kong endured earlier this year may hint at what’s ahead. “They had a really, really bad wave,” Kayoko Shioda, an epidemiologist at Emory University, told me—far dwarfing the four that the city had battled previously. Researchers have estimated that nearly half the city’s population—more than 3 million people—ended up catching the virus. More than 9,000 residents died. And Hong Kong was, in some respects, in a better place to ease its restrictions than the mainland is. This past winter and spring, the city’s main adversary was BA.2, a less vaccine-evasive Omicron subvariant than the ones circulating now; officials had Pfizer’s mRNA-based shot on hand, and quickly began offering fourth doses. Hong Kong also has more ICU beds per capita. Map a new Omicron outbreak onto mainland China, and the prognosis is poor: A recent modeling paper estimated that the country could experience up to 1.55 million deaths in the span of just a few months. (Other analyses offer less pessimistic estimates.)

    Lackluster vaccination isn’t China’s only issue. The country has accumulated almost no infection-induced immunity that might otherwise have updated people’s bodies on recent coronavirus strains. The country’s health-care system is also ill-equipped to handle a surge in demand: For every 100,000 Chinese residents, just 3.6 ICU beds exist, concentrated in wealthier cities; in an out-of-control-infection scenario, even a variant with a relatively low severe-disease risk would prove disastrous, Chen told me. Nor does the system have the slack to accommodate a rush of patients. China’s culture of care seeking is such that “even when you have minor illness, you seek help in urban health centers,” Huang told me, and not enough efforts have been made to bolster triage protocols. More health-care workers may become infected; patients may be more likely to slip through the cracks. Next month’s Lunar New Year celebration, too, could spark further spread. And as the weather cools and restrictions relax, other respiratory viruses, such as RSV and flu, could drive epidemics of their own.

    That said, spikes of illness are unlikely to peak across China at the same time, which could offer some relief. The country’s coming surge “could be explosive,” Cobey told me, “or it could be more of a slow burn.” Already, the country is displaying a patchwork of waxing and waning regulations across jurisdictions, as some cities tighten their restrictions to combat the virus while others loosen up. Experts told me that more measures may return as cases ratchet up—and unlike people in many other countries, the Chinese may be more eager to readopt them to quash a ballooning outbreak.

    Read: China’s zero tolerance for Xi’s COVID restrictions

    A major COVID outbreak in China would also have unpredictable effects on the virus. The world’s most populous country includes a large number of immunocompromised people, who can harbor the virus for months—chronic infections that are thought to have produced variants of concern before. The world may be about to witness “a billion or more opportunities for the virus to evolve,” Cowling told me. In the coming months, the coronavirus could also exploit the Chinese’s close interactions with farmed animals, such as raccoon dogs and mink (both of which can be infected by SARS-CoV-2), and become enmeshed in local fauna. “We’ve certainly seen animal reservoirs becoming established in other parts of the world,” Worobey told me. “We should expect the same thing there.”

    Then again, the risk of new variants spinning out of a Chinese outbreak may be a bit less than it seems, Abdool Karim and other experts told me. China has stuck with zero COVID so long that its population has, by and large, never encountered Omicron subvariants; people’s immune systems remain trained almost exclusively on the original version of the coronavirus, raising only defenses that currently circulating strains can easily get around. It’s possible that “there will be less pressure for the virus to evolve to evade immunity further,” says Emma Hodcroft, a molecular epidemiologist at the University of Bern; and any new versions of the virus that do emerge might not fare particularly well outside of China. In other words, the virus could end up trapped in the very country that tried to keep it out the longest. Still, with so many people susceptible, Cobey told me, there are zero guarantees.

    Either way, viral evolution will plod on—and as it does, the rest of the world may struggle to track it in real time, especially as the cadence of Chinese testing ebbs. Cowling worries that China will have trouble monitoring the number of cases in the country, much less which subvariants are causing them. “There’s going to be a challenge in having situational awareness,” he told me. Shioda, too, worries that China will remain tight-lipped about the scale of the outbreak, a pattern that could have serious implications for residents as well.

    Even without a spike in severe disease, a wide-ranging outbreak is likely to put immense strain on China—which may weigh heavily on its economy and residents for years to come. After the SARS outbreak that began in 2002, rates of burnout and post-traumatic stress among health-care workers in affected countries swelled. Chinese citizens have not experienced an epidemic of this scale in recent memory, Chen told me. “A lot of people think it is over, that they can go back to their normal lives.” But once SARS-CoV-2 embeds itself in the country, it won’t be apt to leave. There will not be any going back to normal, not after this.

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    Katherine J. Wu

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  • The ‘End’ of COVID Is Still Far Worse Than We Imagined

    The ‘End’ of COVID Is Still Far Worse Than We Imagined

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    When is the pandemic “over”? In the early days of 2020, we envisioned it ending with the novel coronavirus going away entirely. When this became impossible, we hoped instead for elimination: If enough people got vaccinated, herd immunity might largely stop the virus from spreading. When this too became impossible, we accepted that the virus would still circulate but imagined that it could become, optimistically, like one of the four coronaviruses that cause common colds or, pessimistically, like something more severe, akin to the flu.

    Instead, COVID has settled into something far worse than the flu. When President Joe Biden declared this week, “The pandemic is over. If you notice, no one’s wearing masks,” the country was still recording more than 400 COVID deaths a day—more than triple the average number from flu.

    This shifting of goal posts is, in part, a reckoning with the biological reality of COVID. The virus that came out of Wuhan, China, in 2019 was already so good at spreading—including from people without symptoms—that eradication probably never stood a chance once COVID took off internationally. “I don’t think that was ever really practically possible,” says Stephen Morse, an epidemiologist at Columbia. In time, it also became clear that immunity to COVID is simply not durable enough for elimination through herd immunity. The virus evolves too rapidly, and our own immunity to COVID infection fades too quickly—as it does with other respiratory viruses—even as immunity against severe disease tends to persist. (The elderly who mount weaker immune responses remain the most vulnerable: 88 percent of COVID deaths so far in September have been in people over 65.) With a public weary of pandemic measures and a government reluctant to push them, the situation seems unlikely to improve anytime soon. Trevor Bedford, a virologist at the Fred Hutchinson Cancer Center, estimates that COVID will continue to exact a death toll of 100,000 Americans a year in the near future. This too is approximately three times that of a typical flu year.

    I keep returning to the flu because, back in early 2021, with vaccine excitement still fresh in the air, several experts told my colleague Alexis Madrigal that a reasonable threshold for lifting COVID restrictions was 100 deaths a day, roughly on par with flu. We largely tolerate, the thinking went, the risk of flu without major disruptions to our lives. Since then, widespread immunity, better treatments, and the less virulent Omicron variant have together pushed the risk of COVID to individuals down to a flu-like level. But across the whole population, COVID is still killing many times more people than influenza is, because it is still sickening so many more people.

    Bedford told me he estimates that Omicron has infected 80 percent of Americans. Going forward, COVID might continue to infect 50 percent of the population every year, even without another Omicron-like leap in evolution. In contrast, flu sickens an estimated 10 to 20 percent of Americans a year. These are estimates, because lack of testing hampers accurate case counts for both diseases, but COVID’s higher death toll is a function of higher transmission. The tens of thousands of recorded cases—likely hundreds of thousands of actual cases every day—also add to the burden of long COVID.

    The challenge of driving down COVID transmission has also become clearer with time. In early 2021, the initially spectacular vaccine-efficacy data bolstered optimism that vaccination could significantly dampen transmission. Breakthrough cases were downplayed as very rare. And they were—at first. But immunity to infection is not durable against common respiratory viruses. Flu, the four common-cold coronaviruses, respiratory syncytial virus (RSV), and others all reinfect us over and over again. The same proved true with COVID. “Right at the beginning, we should have made that very clear. When you saw 95 percent against mild disease, with the trials done in December 2020, we should have said right then this is not going to last,” says Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia. Even vaccinating the whole world would not eliminate COVID transmission.

    This coronavirus has also proved a wilier opponent than expected. Despite a relatively slow rate of mutation at the beginning of the pandemic, it soon evolved into variants that are more inherently contagious and better at evading immunity. With each major wave, “the virus has only gotten more transmissible,” says Ruth Karron, a vaccine researcher at Johns Hopkins. The coronavirus cannot keep becoming more transmissible forever, but it can keep changing to evade our immunity essentially forever. Its rate of evolution is much higher than that of other common-cold coronaviruses. It’s higher than that of even H3N2 flu—the most troublesome and fastest-evolving of the influenza viruses. Omicron, according to Bedford, is the equivalent of five years of H3N2 evolution, and its subvariants are still outpacing H3N2’s usual rate. We don’t know how often Omicron-like events will happen. COVID’s rate of change may eventually slow down when the virus is no longer novel in humans, or it may surprise us again.

    In the past, flu pandemics “ended” after the virus swept through so much of the population that it could no longer cause huge waves. But the pandemic virus did not disappear; it became the new seasonal-flu virus. The 1968 H3N2 pandemic, for example, seeded the H3N2 flu that still sickens people today. “I suspect it’s probably caused even more morbidity and mortality in all those years since 1968,” Morse says. The pandemic ended, but the virus continued killing people.

    Ironically, H3N2 did go away during the coronavirus pandemic. Measures such as social distancing and masking managed to almost entirely eliminate the flu. (It has not disappeared entirely, though, and may be back in full force this winter.) Cases of other respiratory viruses, such as RSV, also plummeted. Experts hoped that this would show Americans a new normal, where we don’t simply tolerate the flu and other respiratory illnesses every winter. Instead, the country is moving toward a new normal where COVID is also something we tolerate every year.

    In the same breath that President Biden said, “The pandemic is over,” he went on to say, “We still have a problem with COVID. We’re still doing a lot of work on it.” You might see this as a contradiction, or you might see it as how we deal with every other disease—an attempt at normalizing COVID, if you will. The government doesn’t treat flu, cancer, heart disease, tuberculosis, hepatitis C, etc., as national emergencies that disrupt everyday life, even as the work continues on preventing and treating them. The U.S.’s COVID strategy certainly seems to be going in that direction. Broad restrictions such as mask mandates are out of the question. Interventions targeted at those most vulnerable to severe disease exist, but they aren’t getting much fanfare. This fall’s COVID-booster campaign has been muted. Treatments such as bebtelovimab and Evusheld remain on shelves, underpublicized and underused.

    At the same time, hundreds of Americans are still dying of COVID every day and will likely continue to die of COVID every day. A cumulative annual toll of 100,000 deaths a year would still make COVID a top-10 cause of death, ahead of any other infectious disease. When the first 100,000 Americans died of COVID, in spring 2020, newspapers memorialized the grim milestone. The New York Times devoted its entire front page to chronicling the lives lost to COVID. It might have been hard to imagine, back in 2020, that the U.S. would come to accept 100,000 people dying of COVID every year. Whether or not that means the pandemic is over, the second part of the president’s statement is harder to argue with: COVID is and will remain a problem.

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    Sarah Zhang

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  • Hundreds of Americans Will Die From COVID Today

    Hundreds of Americans Will Die From COVID Today

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    Over the past week, an average of 491 Americans have died of COVID each day, according to data compiled by The New York Times. The week before, the number was 382. The week before that, 494. And so on.

    For the past five months or so, the United States has trod along something of a COVID-death plateau. This is good in the sense that after two years of breakneck spikes and plummets, the past five months are the longest we’ve gone without a major surge in deaths since the pandemic’s beginning, and the current numbers are far below last winter’s Omicron highs. (Case counts and hospital admissions have continued to fluctuate but, thanks in large part to the protection against severe disease conferred by vaccines and antivirals, they have mostly decoupled from ICU admissions and deaths; the curve, at long last, is flat.) But though daily mortality numbers have stopped rising, they’ve also stopped falling. Nearly 3,000 people are still dying every week.

    We could remain on this plateau for some time yet. Lauren Ancel Meyers, the director of the University of Texas at Austin’s COVID-19 Modeling Consortium, told me that as long as a dangerous new variant doesn’t emerge (in which case these projections would go out the window), we could see only a slight bump in deaths this fall and winter, when cases are likely to surge, but probably—or at least hopefully—nothing too drastic. In all likelihood, though, deaths won’t dip much below their present levels until early 2023, with the remission of a winter surge and the additional immunity that surge should confer. In the most optimistic scenarios that Meyers has modeled, deaths could at that point get as low as half their current level. Perhaps a tad lower.

    Read: How did this many deaths become normal?

    By any measure, that is still a lot of people dying every day. No one can say with any certainty what 2023 might have in store, but as a reference point, 200 deaths daily would translate to 73,000 deaths over the year. COVID would remain a top-10 leading cause of death in America in this scenario, roughly twice as deadly as either the average flu season or a year’s worth of motor-vehicle crashes.

    COVID deaths persist in part because we let them. America has largely decided to be done with the pandemic, even though the pandemic stubbornly refuses to be done with America. The country has lifted nearly all of its pandemic restrictions, and emergency pandemic funding has been drying up. For the most part, people have settled into whatever level of caution or disregard suits them. A Pew Research survey from May found that COVID did not even crack Americans’ list of the top 10 issues facing the country. Only 19 percent said that they consider it a big problem, and it’s hard to imagine that number has gone anywhere but down in the months since. COVID deaths have shifted from an emergency to the accepted collateral damage of the American way of life. Background noise.

    On one level, this is appalling. To simply proclaim the pandemic over is to abandon the vulnerable communities and older people who, now more than ever, bear the brunt of its burden. Yet on an individual level, it’s hard to blame anyone for looking away, especially when, for most Americans, the risk of serious illness is lower now than it has been since early 2020. It’s hard not to look away when each day’s numbers are identically grim, when the devastation becomes metronomic. It’s hard to look each day at a number—491, 382, 494—and experience that number for what it is: the premature ending of so many individual human lives.

    People grow accustomed to these daily tragedies because to not would be too painful. “We are, in a way, victims of our own success,” Steven Taylor, a psychiatrist at the University of British Columbia who has written one book on the psychology of pandemics and is at work on another, told me. Our adaptability is what allowed us to weather the worst of the pandemic, and it is also what’s preventing us from fully escaping the pandemic. We can normalize anything, for better or for worse. “We’re so resilient at adapting to threats,” Taylor said, that we’ve “even habituated to this.”

    Read: America was in an early-death crisis long before COVID

    Where does that leave us? As the nation claws its way out of the pandemic—and reckons with all of its lasting damage—what do we do with the psychic burden of a death toll that might not decline substantially for a long time? Total inurement is not an option. Neither is maximal empathy, the feeling of each death reverberating through you at an emotional level. The challenge, it seems, is to carve out some sort of middle path. To care enough to motivate ourselves to make things better without caring so much that we end up paralyzed.

    Perhaps we will find this path. More likely, we will not. In earlier stages of the pandemic, Americans talked at length about a mythic “new normal.” We were eager to imagine how life might be different—better, even—after a tragedy that focused the world’s attention on disease prevention. Now we’re staring down what that new normal might actually look like. The new normal is accepting 400 COVID deaths a day as The Way Things Are. It’s resigning ourselves so completely to the burden that we forget that it’s a burden at all.

    In the time since you started reading this story, someone in the United States has died of COVID. I could tell you a story about this person. I could tell you that he was a retired elementary-school teacher. That he was planning a trip with his wife to San Diego, because he’d never seen the Pacific Ocean. That he was a long-suffering Knicks fan and baked a hell of a peach cobbler, and when his grandchildren visited, he’d get down on his arthritic knees, and they’d play Connect Four, and he’d always let them win. These details, though hypothetical, might sadden you—or sadden you more, at least, than when I told you simply that since you started this story, one person had died of COVID. But I can’t tell you that story 491 times in one day. And even if I could, could you bear to listen?

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    Jacob Stern

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  • A Simple Rule for Planning Your Fall Booster Shot

    A Simple Rule for Planning Your Fall Booster Shot

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    In less than two weeks, you could walk out of a pharmacy with a next-generation COVID booster in your arm. Just a few days ago, the Biden administration indicated that the first updated COVID-19 vaccines would be available shortly after Labor Day to Americans 12 and older who have already had their primary series. Unlike the shots the U.S. has now, the new doses from Pfizer and Moderna will be bivalent, which means they’ll contain genetic material based both on the ancestral strain of the coronavirus and on two newer Omicron subvariants that are circulating in the U.S.

    These shots’ new formulation promises some level of protection that simply hasn’t been possible with the original vaccines. “A bivalent vaccine will have some benefit for almost everybody who gets it,” Rishi Goel, an immunologist at the University of Pennsylvania, told me. “How much benefit that is, we’re still not exactly sure.” People who aren’t at high risk could end up only marginally more protected against severe outcomes, and no one thinks the shots will banish COVID infections for good. There is, however, a simple rule of thumb that nearly everyone can follow to maximize the uncertain gains from a shot: Wait three to six months from your last COVID infection or vaccination.

    Put that rule into action, and it plays out a little differently, depending on your circumstances.

    If you haven’t had an Omicron infection:

    If you haven’t had COVID since about November 2021, the advantage of a bivalent booster over the original formula is obvious, and as long as you haven’t gotten boosted recently, there’s every reason to get the new one right away. (If you have been boosted in the past few months, your antibody levels are probably still too high for a new shot to do much for you.) Marion Pepper, an immunologist at the University of Washington, told me that Americans who have already gotten three or more doses “have probably maxed out the protective capacity” of the original shots. By contrast, the bivalent vaccines offer something new to those who have so far escaped Omicron: a lesson on the spike proteins of the BA.4 and BA.5 subvariants, which will help the immune system fight the real thing should it get into your body. “I’m just super excited to get the bivalent vaccine,” says Jenna Guthmiller, an immunologist at the University of Colorado who has not yet had COVID. “I think it’ll be really nice and ease my mind a little bit.”

    Read: The pandemic’s soft closing

    If you have had an Omicron infection:

    Veterans of Omicron infections might still have something to gain from seeing the BA.4 and BA.5 spike proteins—especially if your goal is to avoid getting sick with COVID at all. Past a certain number of shots, boosters’ impact on your long-term protection against severe disease is unclear, Goel told me. Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told me he doesn’t plan on getting a booster at all this fall because, after three vaccine doses and an infection, “I think I’m protected against serious illness.” But if you want to stave off infection, Goel said, “the bivalent vaccines, or really any variant-containing vaccines, have real value.” That’s because formulas based on a given variant have been shown to temporarily increase your stock of antibodies that target that variant.

    How long that extra-protective state lasts, or whether it’s sufficient to prevent any infection whatsoever, is still a scientific puzzle. The original boosters were shown to increase antibody levels to a peak about two weeks after the shot, then decay steadily over the following three months. We don’t know yet whether a bivalent formula will change that timeline, Goel said.

    But you can still use it to estimate approximately when your protection will be at its highest. You might, for example, choose to err on the early side of that three-to-six-month timeline if you have a particularly high-risk event coming up in the next few weeks. “If all we had was the original booster and I was going to an indoor wedding or something, I think it would be reasonable to get that booster,” Pepper said.

    Read: The BA.5 wave is what COVID normal looks like

    If you had an Omicron infection this summer:

    “You’re still riding the wave of antibodies that you generated as a result of that infection,” Guthmiller told me, so a shot won’t do much for you yet. That’s true regardless of which Omicron subvariant you might have been infected with, she said, because BA.2 infections have been shown to protect fairly well against today’s dominant strains, BA.4 and BA.5. (BA.2 became dominant in the United States back in March.) The severity of your illness doesn’t really matter either, Goel said. A higher fever and more intense cough might indicate that your immune system got extra revved up, he said, but they could just as easily mean that your body needs more help responding to the coronavirus. In either case, once a little more time has passed, getting the bivalent vaccine could help extend your body’s memory of its last COVID encounter, and keep infection at bay.

    If you’re at high risk:

    Certain groups of people should get any booster as soon as it’s available to them, the experts I spoke with emphasized to me: immunocompromised people, people over the age of 50 or so, and people with medical conditions that put them at high risk of severe disease. If you fall in one of these categories and haven’t received all the boosters you’re eligible for, “I wouldn’t wait for the bivalent,” Offit said. For people in these high-risk categories who have already gotten the recommended number of boosters, you should get the new one as soon as it’s available to you. (The FDA and CDC have not yet indicated whether they will recommend a waiting period between your most recent shot and the bivalent booster.) Goel recommended waiting at least a month after your most recent infection or shot, but if you’re very worried about your risk, you don’t need to stretch the delay to three months. Your body might still have extra antibodies floating around, but with no practical way to check at scale, “I’m honestly in favor of recommending boosting as a way to maximize individual benefit,” he said.

    Read: America’s fall booster plan has a fatal paradox

    If you want to wait and see:

    Waiting is always an option if you want to know more about how the bivalent vaccines perform. The FDA and CDC are set to green-light the shots based on human data from the existing boosters and other experimental bivalent boosters that didn’t make it to market in the U.S.—plus trials on the new formula in mice. Pfizer and Moderna simply haven’t progressed very far in their human trials. While there’s no reason to suspect that the new shots won’t be safe, Offit recommended opting for the original boosters until more safety and efficacy data are available, which could be as soon as a couple of months after the rollout—as long as the vaccine makers or the government collects that information and makes it public. But Guthmiller and Goel said they weren’t concerned about the lack of human data, and the bivalent shot is almost certainly the better bet.

    There is one significant reason to avoid waiting too long for the bivalent shot: It offers the greatest protection against infection from the subvariants it’s actually designed around. BA.4 and BA.5 might be with us through the fall and winter—or they might give way to a different branch of Omicron, or even a variant that’s entirely unlike Omicron. You’d certainly be better off against this new variant with a bivalent booster than no booster at all. But if you want to maximize your anti-infection shield while you have it, consider putting it up against the enemy you know.

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    Rachel Gutman-Wei

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