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Tag: COVID vaccines

  • NJ Department of Health takes action to ensure access to COVID vaccines

    NEW JERSEY (WABC) — A week after Gov. Kathy Hochul signed an executive order allowing New Yorkers easier access to COVID vaccines, New Jersey is now following suit.

    The New Jersey Department of Health issued an executive directive on Tuesday, allowing anyone six months of age and older to receive a COVID shot if they want one.

    The department also issued a standing order authorizing pharmacists in the state to administer the shots without a prescription.

    “At a time when COVID-19 cases are increasing across the country and as part of my Administration’s dedication to evidence-based public health action, I am committed to ensuring everyone in New Jersey who wants to receive a COVID-19 vaccination can receive a dose this fall from trusted health professionals,” New Jersey Governor Phil Murphy said.

    The actions come in time for respiratory virus season and amid increases in reported COVID-19 cases across the country.

    RELATED | FAQs about COVID-19 vaccines

    It also comes after the Food and Drug Administration (FDA) approved updated versions of the COVID vaccine but authorized them only for people 65 and older or for people who have an underlying medical condition.

    The move prompted Gov. Hochul to sign an executive order last Friday allowing New Yorkers to get a COVID vaccine at pharmacies in the state without a prescription.

    As for New Jersey, the Department of Heath said new vaccines are expected to be available in some locations in the state now, and statewide in the coming weeks.

    To locate a vaccination provider, visit Vaccines.gov. The department says New Jerseyans can expect vaccines to be available from sites like primary care providers, chain pharmacies, Federally Qualified Health Centers, and other health care institutions.

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  • Why Are We Still Flu-ifying COVID?

    Why Are We Still Flu-ifying COVID?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    Katherine J. Wu

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  • We Can Finally Do Something About the Third ‘Tripledemic’ Virus

    We Can Finally Do Something About the Third ‘Tripledemic’ Virus

    Every fall, when the air turns chilly and the leaves red, pediatric ICUs begin preparing for the onslaught of the virus known as RSV. Not flu, not COVID, but RSV, or respiratory syncytial virus, is the No. 1 reason babies are hospitalized, year after year. Their tiny airways can become inflamed, and the sickest ones struggle to breathe. RSV is deadly on the other end of the age spectrum too, killing 6,000 to 10,000 elderly Americans every year.

    For decades though, there was no way to stop the virus’s seasonal tide. The quest for a vaccine always came up short. And then suddenly, the vaccines started working.

    This year, doctors have not just one but multiple new shots to prevent RSV. Three gained FDA approval in rapid succession in recent months: an antibody shot for infants called nirsevimab, a form of passive immunization for babies too young to get proper vaccines; a vaccine from Pfizer for both adults over 60 and pregnant mothers, who can pass the immunity on to their babies; and finally, a vaccine from GlaxoSmithKline also aimed at adults older than 60. Together, these herald a new era for RSV.

    That these three new RSV shots are coming out at once is no coincidence. They succeed where others failed because they all target a specific weak spot in the virus, first identified in 2013. This strategy of finding a virus’s most vulnerable points applies to other pathogens too, and experts say it can revolutionize the design of vaccines for other diseases. In fact, it was quietly used to make the COVID vaccines from Pfizer and Moderna. Scientists had originally perfected the idea with RSV, only to repurpose it for the COVID vaccine, which raced ahead, given the urgency of the pandemic. This year, though, the shots are coming for RSV.

    “We’re in a really good position, finally, after more than 65 years,” says Asunción Mejías, an infectious-diseases doctor at St. Jude Children’s Research Hospital.


    The first attempts to make an RSV vaccine began not long after the virus’s discovery, in 1956, but an early trial ended so catastrophically that it had a chilling effect for decades.

    It had started off with promise. The early vaccine was modeled after a successful one for polio, in which the virus is inactivated with a chemical called formalin. But when infants given the early RSV vaccine later caught the virus, a whopping 80 percent had to be hospitalized—compared with only 5 percent in the control group. Two of the babies died, their lungs ravaged. The vaccine did worse than offer no protection; it made the disease more severe. “It was such a disaster,” says Ann Falsey, an infectious-diseases doctor at the University of Rochester. Scientists spent years piecing together why—the vaccine riled up the wrong part of the immune system in very young babies—but they got no closer to making a vaccine that worked. The field was stuck.

    Then, in 2008, a serendipitous meeting led to an eventual breakthrough. A young, freshly minted Ph.D. named Jason McLellan, who studies the structure of proteins, began a new job at the National Institutes of Health to work on HIV vaccines. The lab he had joined, on the fourth floor, had run out of room, though, so he got put in another, on the second. There, he ran into Barney Graham, a virologist who had been trying to solve the puzzle of RSV since the 1980s. He convinced McLellan that this virus was worth a look too.

    By then, scientists had at least homed in on a plausible vaccine target. Much as COVID uses spike protein to infect cells, RSV uses a protein—called F for “fusion”—to physically fuse the virus particle to a human cell. F comes in two forms, though: an extremely unstable prefusion state and a far more stable postfusion state. And once it switches to the postfusion state—which can also happen spontaneously— “it can’t come back,” McLellan told me.

    When RSV vaccines are manufactured, all the F protein eventually switches to the postfusion state. But the antibodies against postfusion F weren’t very effective. McLellan soon figured out why. He found that extremely potent neutralizing antibodies bind to a specific site—the very tip of the prefusion F—that is lost when the protein rearranges into its postfusion form. With that, Graham told me, “you lose ten- to 1,000-fold potency.” An effective RSV vaccine would need to target the prefusion F.

    The team knew what to do, but had a practical dilemma: How to stabilize F in its prefusion form, so the team could put it in a vaccine? McLellan rejiggered the protein slightly, adding molecular “staples” and filling a hole in the protein structure. These changes froze F in its prefusion shape. When the team tested this version of the vaccine in mice, the results could not have been clearer. The vaccine induced the highest levels of neutralizing antibodies Graham had ever seen in his three decades of studying RSV. “This is it,” McLellan remembers thinking.

    Soon, pharmaceutical companies came calling, and the race was on. (The experts in this article—like nearly everyone who works on RSV vaccines—have all received research grants, consulted for, or worked in some other way with one or more of the companies developing shots for RSV.) Today, Pfizer’s and GlaxoSmithKline’s newly approved RSV vaccines target the prefusion F protein, as does nirsevimab, the antibody shot for infants from AstraZeneca and Sanofi. Both the vaccines and the antibody shot trigger immunity against RSV: Vaccines stimulate the immune system to make its own antibodies, and nirsevimab is a direct infusion of antibodies.

    Trials for all three shots were already under way when the coronavirus pandemic hit. But because RSV nearly disappeared during social distancing, the trials got delayed. Meanwhile, McLellan and Graham devised a similar molecular trick to stabilize COVID’s spike protein, which Pfizer and Moderna later used in their vaccines. (The stabilization wasn’t make-or-break for COVID, as it was for RSV, though—AstraZeneca’s COVID vaccine was effective despite not having this modification.) But unstable fusion proteins are found in many different classes of viruses beyond RSV. McLellan, now at the University of Texas at Austin, is working on shots against the prefusion structure of other stubborn viruses such as cytomegalovirus and Crimean-Congo hemorrhagic fever. (Graham is now a professor at Morehouse School of Medicine.) This approach—called structure-based vaccine design—could unlock new ways of targeting once-elusive viruses.


    For RSV, this fall and winter will be a test of how well the shots fare in the real world. As the adage goes, vaccines don’t save lives; vaccinations do. Falsey, the University of Rochester doctor, specializes in studying RSV in the elderly, and she worries that too few Americans over 60 will get the new vaccines this year. A CDC advisory panel decided that elderly Americans can get the vaccines through “shared clinical decision-making” with their doctors but did not go as far as to fully recommend vaccination, which would have triggered private insurers to cover the shots under the Affordable Care Act. Out of pocket, they can cost more than $300. The vaccine for pregnant women, meanwhile, has FDA approval, but the same CDC panel is voting today on whether to recommend it. The panel will likely scrutinize a possible link to premature births, which has shown up before with RSV vaccines.

    Nirsevimab, the antibody shot for infants, has gotten a full-throated endorsement, though, and it’s poised to have the biggest impact this season. It replaces an existing RSV-antibody shot called palivizumab, which is not widely used. Palivizumab targets a less potent site that is on both the pre- and postfusion F, and it needs to be administered up to five times a season (compared with once for nirsevimab), at a cost of some $1,500 a dose. For these reasons, it’s been reserved for the highest-risk babies, such as preemies with underdeveloped lungs. But most babies who end up hospitalized were healthy to begin with, says St. Jude’s Mejías, so the older shot didn’t put much of a dent in overall hospitalizations.

    Nirsevimab is meant to be more widely used: The shot is approved for all infants in their first RSV season. “It’s going to change the way we manage and treat RSV,” Mejías told me. It should be available for babies starting in October. And if all goes according to plan, pediatric ICUs could be a little quieter this winter.

    Sarah Zhang

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

    What Should Go Into This Year’s COVID Vaccine?

    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.

    Katherine J. Wu

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  • Vaccination Could Reduce Risk of Long COVID, Study Shows

    Vaccination Could Reduce Risk of Long COVID, Study Shows

    Feb. 15, 2023 – After studying thousands of people’s symptoms post-COVID-19, researchers have found that getting vaccinated could potentially reduce the risk of long COVID. 

    The new study – which looked at patients 3 months after their COVID-19 infections across pre-Delta, Delta, and Omicron variants – at first saw that long COVID symptoms were more common in the pre-Delta period than in the Delta and Omicron periods. But these differences across variants became less important when researchers adjusted for vaccination status, suggesting that the vaccine could play a key role in lessening the risk of long COVID and making its symptoms less severe. 

    Another important finding of the study, from researchers at Chicago’s Rush University Medical Center and the University of California San Francisco and published in the journal Clinical Infectious Diseases, was the sheer number of people post-COVID-19 who reported severe fatigue. 

    “Mild fatigue is much different than severe, life-impacting fatigue,” lead author Michael Gottlieb, MD, said at a media briefing Wednesday. “One in eight affected with COVID had severe, prolonged fatigue at 3 months. … That speaks to the impact we’re seeing as a society.” 

    The study included 2,402 COVID-positive and 821 COVID-negative people, with 463 falling into the pre-Delta category, 1,198 during Delta, and 741 during Omicron. 

    The authors did not weigh how severe the  patients’ initial COVID infections were versus their prolonged symptoms, but Gottlieb told reporters that the group is currently working on supplemental survey research to see if there are any parallels between the two. 

    Gottlieb said the research team is continuing to follow patients beyond the 3-month mark, to see what the paths of their symptoms look like. Some early data, he said, shows patients’ symptoms going in both directions: Some people who have minimal symptoms at 3 months might convert to severe symptoms at 6 months, and others with severe symptoms at 3 months might be better at 6 months. 

    All of these lingering questions, including how reinfection plays into long COVID, will be the focus of future research for Gottlieb’s team. 

    “We need to understand long COVID better, and we need to define it better,” Gottlieb said. “Long COVID isn’t a singular concept, there are different phenotypes and versions of it. As researchers, public health leaders, and as a society, we need to better understand what people are going through.” 

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  • COVID Vaccines Are Turning Into Flu Shots

    COVID Vaccines Are Turning Into Flu Shots

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

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

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

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

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

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

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

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

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

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

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

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

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

    Katherine J. Wu

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  • Is the Worst of Winter Over for COVID?

    Is the Worst of Winter Over for COVID?

    For months, the winter forecast in the United States seemed to be nothing but viral storm clouds. A gale of RSV swept in at the start of autumn, sickening infants and children in droves and flooding ICUs. After a multiyear hiatus, flu, too, returned in force, before many Americans received their annual shot. And a new set of fast-spreading SARS-CoV-2 subvariants had begun its creep around the world. Experts braced for impact: “My biggest concern was hospital capacity,” says Katelyn Jetelina, who writes the popular public-health-focused Substack Your Local Epidemiologist. “If flu, RSV, and COVID were all surging at the same time—given how burned out, how understaffed our hospital systems are right now—how would that pan out?”

    But the season’s worst-case scenario—what some called a “tripledemic,” bad enough to make health-care systems crumble—has not yet come to pass. Unlike last year, and the year before, a hurricane of COVID hospitalizations and deaths did not slam the country during the first month of winter; flu and RSV now appear to be in sustained retreat. Even pediatric hospitals, fresh off what many described as their most harrowing respiratory season in memory, finally have some respite, says Mary Beth Miotto, a pediatrician and the president of the Massachusetts chapter of the American Academy of Pediatrics. After a horrific stint, “we are, right now, doing okay.” With two months to go until spring, there is plenty of time for another crisis to emerge: Certain types of influenza, in particular, can be prone to delivering late-season second peaks. “We need to be careful and recognize we’re still in the middle,” Jetelina told me. But so far, this winter “has not been as bad as I expected it to be.”

    No matter what’s ahead, this respiratory season certainly won’t go down in history as a good one. Children across the country have fallen sick in overwhelming numbers, many of them with multiple respiratory viruses at once, amid a nationwide shortage of pediatric meds. SARS-CoV-2 remains a top cause of mortality, with its daily death count still in the hundreds, and long COVID continues to be difficult to prevent or treat. And enthusiasm for new vaccines and virus-blocking mitigations seems to be at an all-time low. Any sense of relief people might be feeling at this juncture must be tempered by what’s in the rearview: three years of an ongoing pandemic that has left more than 1 million people dead in the U.S. alone, and countless others sick, many chronically so. The winter may be going better than it could have. But that shouldn’t hold us back from tackling what’s ahead this season, and in others yet to come.

    Not all of this past autumn’s gloomy predictions were off base. RSV and flu each rushed in on the early side of the season and led to a steep rise in cases. But both viruses made rather hasty exits: RSV hit an apparent apex in mid-November, and flu bent into its own decline the following month. The staggered peaks “helped us quite a bit, in terms of hospitals being stressed,” says Sam Scarpino, the director of AI and life sciences at the Institute for Experiential AI at Northeastern University. In recent days, coronavirus cases and hospitalizations have been tilting downward, too—and severe-disease rates seem to be holding at a relative low. Just under 5 percent of hospital beds are currently occupied by COVID patients, compared with more than four times that fraction this time last year. And weekly COVID deaths are down by almost 75 percent from January 2022. (Death, though, has always been a lagging indicator, and the mortality numbers could still shift upward soon.) Despite some dire predictions to the contrary, the fast-spreading XBB.1.5 subvariant didn’t spark “some giant Omicron-type wave and crush everything,” says Justin Lessler, an infectious-disease modeler at the University of North Carolina at Chapel Hill. “In that sense, I feel good.”

    No one can say for sure why we dodged winter’s deadliest bullets, but the population-level immunity that Americans have built up over the past three years clearly played a major role. “That’s a testament to how vaccination has made the disease less dangerous for most people,” says Cedric Dark, an emergency physician at Baylor College of Medicine. Widespread immunization, combined with the fact that most Americans have now been infected, and many of them reinfected, has caused severe-disease rates to plunge, and the virus to move less quickly than it otherwise would have. Antiviral drugs, too, have been slashing hospitalization rates, at least for the meager fraction of recently infected people who use them. The gargantuan asterisk of long COVID still applies to new infections, but the short-term effects of the disease are now more on par with those of other respiratory illnesses, reducing the number of resources that health-care workers must marshal for each case.

    The virus, too, was more merciful than it could have been. XBB.1.5, despite its high transmissibility and penchant for dodging antibodies, doesn’t so far seem more capable of causing severe disease. And the fall’s bivalent shots, though not a perfect match for the newcomer, still improve the body’s response to viruses in the Omicron clan. Competition among respiratory viruses may have also helped soften COVID’s recent blows. In the days and weeks after one infection, bodies can become more resilient to another—a phenomenon known as viral interference that can reduce the risk of simultaneous or back-to-back infections. On population scales, interference can push down surges’ peaks, or at the very least, separate them, potentially keeping hospitals from being hit by a medley of microbes all at once. It’s hard to say for sure: “Many things go into when an epidemic wave happens—human behavior, temperature, humidity, the biology of the virus, the biology of the host,” says Ellen Foxman, an immunologist at Yale. That said, “I do think viral interference probably does play a role that has not been appreciated.”

    None of the experts I spoke with was ready to issue a blanket phew. Overlapping waves of respiratory illness have already led to nonstop sickness, especially among children, draining resources at every point in the pediatric caregiving chain. Kids were kept out of school, and parents stayed home from work; after a glut of COVID-related closures in New Mexico, schools and day cares running low on teachers had to call in the National Guard. Inundated with illnesses, pediatric emergency rooms overflowed; adult-care units had to be repurposed for children, and some hospitals pitched tents on their front lawns to accommodate overflow. Local stopgaps weren’t always enough: At one point, a colleague of Miotto’s in Boston told her that the closest available pediatric ICU bed was in Washington, D.C.

    By any metric, for the pediatric community, “it’s been a horrible season, the worst,” says Yvonne Maldonado, a pediatrician at Stanford. “The hospitals were bursting, bursting at the seams.” The flow of fevers has ebbed somewhat in recent weeks, but remains more flood than trickle. “It’s not over: We still don’t have amoxicillin in general, and we still struggle to get fever medication for people,” Miotto said. A parent recently told her that they’d gone to almost 10 pharmacies to try to fill an antibiotic prescription for their child. And pediatric providers across the country are steeling themselves for what the coming weeks could bring. “I think we could still see another surge,” says Joelle Simpson, the division chief of emergency medicine at Children’s National Hospital. “In prior years, February has been one of the worst months.”

    The season’s ongoing woes have been compounded by preexisting health-care shortages. Amid a dearth of funds, some hospitals have reduced their number of pediatric beds; a mass exodus of workers has also limited the resources that can be doled out, even as SARS-CoV-2 testing and isolation protocols continue to stretch the admission and discharge timeline. “Hospitals are in a weaker position than they were before the pandemic,” says Joseph Kanter, Louisiana’s state health officer and medical director. “If that’s the environment in which we are experiencing this year’s respiratory-virus season, it makes everything feel more acute.” Those issues are not limited to pediatrics: Now that COVID is a regular part of the disease roster, workloads have increased for a contingent of beleaguered clinicians that, across the board, seems likely to continue to shrink. In many hospitals, patients are getting stuck in emergency departments for several hours, even multiple days—sometimes never making it to a bed before being sent home. “It seems like hospitals everywhere are full,” Dark told me, not just because of COVID, but because of everything. “The vast majority of the work I do, and that I bet you what most of my colleagues are doing, is taking place in waiting rooms.”

    The U.S. has come a long way in the past three years. But still, “the cumulative toll of these winter surges has been higher than it needs to be,” says Julia Raifman, a health-policy researcher at Boston University. Had more people gone into winter up to date on their COVID vaccines, the virus’s mortality rate could have been driven down further; had more antiviral drugs and other protections been prioritized for the elderly and immunocompromised, fewer people might have been imperiled at all. If relief is percolating across the country right now, that says more about a shift in standards than anything else. “Our threshold for what ‘bad’ looks like has just gotten so out of whack,” Simpson told me. This winter could have been as grim as recent ones, Scarpino told me, with body-filled freezer trucks in parking lots and hospitals on the brink of collapse. But an improvement from those horrific lows isn’t much to brag about. And this winter—three years into combatting a coronavirus for which we have shots, drugs, masks, and more—has been nowhere close to the best one imaginable.

    The concern now, experts told me, is that the U.S. might accept a winter like this one as simply good enough. Regular vaccine uptake could dwindle even further; another wild-card SARS-CoV-2 variant could ignite another conflagration of cases. If that did happen, some researchers worry that we’d be slow to notice: Genomic surveillance is down, and many tests are being taken, unreported, at home. And with so many different immune histories now scattered across the globe, it’s getting tougher for modelers like Lessler to predict where and how quickly new variants might take over.

    The country does have a few factors working in its favor. By next winter, at least one RSV vaccine will almost certainly be available to protect the population’s youngest, eldest, or both. mRNA-based flu vaccines, which are expected to be far faster to develop than currently available shots, are also in the works, and will likely make it easier to match doses to circulating strains. And if, as Foxman hopes, SARS-CoV-2 eventually settles into a more predictable, seasonal pattern, infections will be less of a concern for most of the year and season-specific immunizations could be easier to design.

    But no vaccine will do much unless enough people are willing and able to take it—and the public-health infrastructure that’s led many outreach efforts remains underfunded and understaffed. Kanter worries that the nation may not be terribly willing to invest. “We’ve fallen into this complacency trap where we just accept a given amount of mortality every year as unavoidable,” he told me. It doesn’t have to be that way, as the past few years have shown: Treatments, vaccines, clean indoor air, and other measures can lower a respiratory virus’s toll.

    By the middle of spring, the U.S. will be in a position to let the public-health-emergency declaration on COVID lapse—a decision that could roll back protections for the uninsured, and ratchet up price points on shots and antivirals. This winter’s retrospective is likely to influence that decision, Scarpino told me. But relief can breed complacency, and complacency further slows a sluggish public-health response. The fate of next winter—and of every winter after that—will depend on whether the U.S. decides to view this season as a success, or to recognize it as a shaky template for well-being that can and should be improved.

    Katherine J. Wu

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  • Is COVID Immunity Hung Up on Old Variants?

    Is COVID Immunity Hung Up on Old Variants?

    In the two-plus years that COVID vaccines have been available in America, the basic recipe has changed just once. The virus, meanwhile, has belched out five variants concerning enough to earn their own Greek-letter names, followed by a menagerie of weirdly monikered Omicron subvariants, each seeming to spread faster than the last. Vaccines, which take months to reformulate, just can’t keep up with a virus that seems to reinvent itself by the week.

    But SARS-CoV-2’s evolutionary sprint might not be the only reason that immunity can get bogged down in the past. The body seems to fixate on the first version of the virus that it encountered, either through injection or infection—a preoccupation with the past that researchers call “original antigenic sin,” and that may leave us with defenses that are poorly tailored to circulating variants. In recent months, some experts have begun to worry that this “sin” might now be undermining updated vaccines. At an extreme, the thinking goes, people may not get much protection from a COVID shot that is a perfect match for the viral variant du jour.

    Recent data hint at this possibility. Past brushes with the virus or the original vaccine seem to mold, or even muffle, people’s reactions to bivalent shots—“I have no doubt about that,” Jenna Guthmiller, an immunologist at the University of Colorado School of Medicine, told me. The immune system just doesn’t make Omicron-focused antibodies in the quantity or quality it probably would have had it seen the updated jabs first. But there’s also an upside to this stubbornness that we could not live without, says Katelyn Gostic, an immunologist and infectious-disease modeler who has studied the phenomenon with flu. Original antigenic sin is the reason repeat infections, on average, get milder over time, and the oomph that enables vaccines to work as well as they do. “It’s a fundamental part,” Gostic told me, “of being able to create immunological memory.”

    This is not just basic biology. The body’s powerful first impressions of this coronavirus can and should influence how, when, and how often we revaccinate against it, and with what. Better understanding of the degree to which these impressions linger could also help scientists figure out why people are (or are not) fighting off the latest variants—and how their defenses will fare against the virus as it continues to change.


    The worst thing about “original antigenic sin” is its name. The blame for that technically lies with Thomas Francis Jr., the immunologist who coined the phrase more than six decades ago after noticing that the initial flu infections people weathered in childhood could bias how they fared against subsequent strains. “Basically, the flu you get first in life is the one you respond to most avidly for the long term,” says Gabriel Victora, an immunologist at Rockefeller University. That can become somewhat of an issue when a very different-looking strain comes knocking.

    In scenarios like these, original antigenic sin may sound like the molecular equivalent of a lovesick teen pining over an ex, or a student who never graduates out of immunological grade school. But from the immune system’s point of view, never forgetting your first is logically sound. New encounters with a pathogen catch the body off guard—and tend to be the most severe. A deep-rooted defensive reaction, then, is practical: It ups the chances that the next time the same invader shows up, it will be swiftly identified and dispatched. “Having good memory and being able to boost it very quickly is sometimes a very good thing,” Victora told me. It’s the body’s way of ensuring that it won’t get fooled twice.

    These old grudges come with clear advantages even when microbes morph into new forms, as flu viruses and coronaviruses often do. Pathogens don’t remake themselves all at once, so immune cells that home in on familiar snippets of a virus can still in many cases snuff out enough invaders to prevent an infection’s worst effects. That’s why even flu shots that aren’t perfectly matched to the season’s most prominent strains are usually still quite good at keeping people out of hospitals and morgues. “There’s a lot of leniency in how much the virus can change before we really lose protection,” Guthmiller told me. The wiggle room should be even bigger, she said, with SARS-CoV-2, whose subvariants tend to be far more similar to one another than, say, different flu strains are.

    With all the positives that immune memory can offer, many immunologists tend to roll their eyes at the negative and bizarrely moralizing implications of the phrase original antigenic sin. “I really, really hate that term,” says Deepta Bhattacharya, an immunologist at the University of Arizona. Instead, Bhattacharya and others prefer to use more neutral words such as imprinting, evocative of a duckling latching onto the first maternal figure it spots. “This is not some strange immunological phenomenon,” says Rafi Ahmed, an immunologist at Emory University. It’s more a textbook example of what an adaptable, high-functioning immune system does, and one that can have positive or negative effects, depending on context. Recent flu outbreaks have showcased a little bit of each: During the 2009 H1N1 pandemic, many elderly people, normally more susceptible to flu viruses, fared better than expected against the late-aughts strain, because they’d banked exposures to a similar-looking H1N1—a derivative of the culprit behind the 1918 pandemic—in their youth. But in some seasons that followed, H1N1 disproportionately sickened middle-aged adults whose early-life flu indoctrinations may have tilted them away from a protective response.

    The backward-gazing immune systems of those adults may have done more than preferentially amplify defensive responses to a less relevant viral strain. They might have also actively suppressed the formation of a response to the new one. Part of that is sheer kinetics: Veteran immune cells, trained up on past variants and strains, tend to be quicker on the draw than fresh recruits, says Scott Hensley, an immunologist at the Perelman School of Medicine at the University of Pennsylvania. And the greater the number of experienced soldiers, the more likely they are to crowd out rookie fighters—depriving them of battlefield experience they might otherwise accrue. Should the newer viral strain eventually return for a repeat infection, those less experienced immune cells may not be adequately prepared—leaving people more vulnerable, perhaps, than they might otherwise have been.

    Some researchers think that form of imprinting might now be playing out with the bivalent COVID vaccines. Several studies have found that the BA.5-focused shots are, at best, moderately more effective at producing an Omicron-targeted antibody response than the original-recipe jab—not the knockout results that some might have hoped for. Recent work in mice from Victora’s lab backs up that idea: B cells, the manufacturers of antibodies, do seem to have trouble moving past the impressions of SARS-CoV-2’s spike protein that they got from first exposure. But the findings don’t really trouble Victora, who gladly received his own bivalent COVID shot. (He’ll take the next update, too, whenever it’s ready.) A blunted response to a new vaccine, he told me, is not a nonexistent one—and the more foreign a second shot recipe is compared with the first, the more novice fighters should be expected to participate in the fight. “You’re still adding new responses,” he said, that will rev back up when they become relevant. The coronavirus is a fast evolver. But the immune system also adapts. Which means that people who receive the bivalent shot can still expect to be better protected against Omicron variants than those who don’t.

    Historical flu data support this idea. Many of the middle-aged adults slammed by recent H1N1 infections may not have mounted perfect attacks on the unfamiliar virus, but as immune cells continued to tussle with the pathogen, the body “pretty quickly filled in the gaps,” Gostic told me. Although it’s tempting to view imprinting as a form of destiny, “that’s just not how the immune system works,” Guthmiller told me. Preferences can be overwritten; biases can be undone.


    Original antigenic sin might not be a crisis, but its existence does suggest ways to optimize our vaccination strategies with past biases in mind. Sometimes, those preferences might need to be avoided; in other instances, they should be actively embraced.

    For that to happen, though, immunologists would need to fill in some holes in their knowledge of imprinting: how often it occurs, the rules by which it operates, what can entrench or alleviate it. Even among flu viruses, where the pattern has been best-studied, plenty of murkiness remains. It’s not clear whether imprinting is stronger, for instance, when the first exposure comes via infection or vaccination. Scientists can’t yet say whether children, with their fiery yet impressionable immune systems, might be more or less prone to getting stuck on their very first flu strain. Researchers don’t even know for certain whether repetition of a first exposure—say, through multiple doses of the same vaccine, or reinfections with the same variant—will more deeply embed a particular imprint.

    It does seem intuitive that multiple doses of a vaccine could exacerbate an early bias, Ahmed told me. But if that’s the case, then the same principle might also work the other way: Maybe multiple exposures to a new version of the virus could help break an old habit, and nudge the immune system to move on. Recent evidence has hinted that people previously infected with an early Omicron subvariant responded more enthusiastically to a bivalent BA.1-focused vaccine—available in the United Kingdom—than those who’d never encountered the lineage before. Hensley, at the University of Pennsylvania, is now trying to figure out if the same is true for Americans who got the BA.5-based bivalent shot after getting sick with one of the many Omicron subvariants.

    Ahmed thinks that giving people two updated shots—a safer approach, he points out, than adding an infection to the mix—could untether the body from old imprints too. A few years ago, he and his colleagues showed that a second dose of a particular flu vaccine could help shift the ratio of people’s immune responses. A second dose of the fall’s bivalent vaccine might not be practical or palatable for most people, especially now that BA.5 is on its way out. But if next autumn’s recipe overlaps with BA.5 in ways that it doesn’t with the original variant—as it likely will to at least some degree, given the Omicron lineage’s continuing reign—a later, slightly different shot could still be a boon.

    Keeping vaccine doses relatively spaced out—on an annual basis, say, à la flu shots—will likely help too, Bhattacharya said. His recent studies, not yet published, hint that the body might “forget” old variants, as it were, if it’s simply given more time: As antibodies raised against prior infections and injections fall away, vaccine ingredients could linger in the body rather than be destroyed by prior immunity on sight. That slightly extended stay might offer the junior members of the immune system—lesser in number, and slower on the uptake—more of an opportunity to cook up an Omicron-specific response.

    In an ideal world, researchers might someday know enough about imprinting to account for its finickiness whenever they select and roll out new shots. Flu shots, for instance, could be personalized to account for which strains babies were first exposed to, based on birth year; combinations of COVID vaccine doses and infections could dictate the timing and composition of a next jab. But the world is not yet living that reality, Gostic told me. And after three years of an ever-changing coronavirus and a fluctuating approach to public health, it’s clear that there won’t be a single vaccine recipe that’s ideal for everyone at once.

    Even Thomas Francis Jr. did not consider original antigenic sin to be a total negative, Hensley told me. According to Francis, the true issue with the “sin” was that humans were missing out on the chance to imprint on multiple strains at once in childhood, when the immune system is still a blank slate—something that modern researchers could soon accomplish with the development of universal vaccines. Our reliance on first impressions can be a drawback. But the same phenomenon can be an opportunity to acquaint the body with diversity early on—to give it a richer narrative, and memories of many threats to come.

    Katherine J. Wu

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  • Add COVID Shot to Routine Vaccine Schedule: CDC Panel

    Add COVID Shot to Routine Vaccine Schedule: CDC Panel

    By Cara Murez and Robin Foster 

    HealthDay Reporters

    FRIDAY, Oct. 21, 2022 (HealthDay News) – In an unanimous vote on Thursday, a panel of U.S. vaccine experts recommended that COVID shots be added to the list of recommended vaccinations for children and adults.

    Now it’s up to the U.S. Centers of Disease Control and Prevention to decide whether to follow the advice of its Advisory Committee on Immunization Practices.

    Even if the agency does approve adding the shots to the schedule, it doesn’t amount to a vaccine mandate. State and local jurisdictions will still decide what vaccines are required for schools, NBC News reported.

    “Moving COVID-19 to the recommended immunization schedule does not impact what vaccines are required for school entrance, if any,” said Dr. Nirav Shah, director of the Maine Center for Disease Control and Prevention. “Local control matters. And we honor that the decision around school entrance for vaccines rests where it did before, which is with the state level, the county level and at the municipal level, if it exists at all.”

    “This discussion does not change that,” he told NBC News.

    An example of local jurisdictions making their own choices includes the HPV vaccine, which has been on the immunization schedule since 2006. Only Puerto Rico, Rhode Island and Washington, D.C., actually require it for both girls and boys. Virginia requires the vaccine for girls, NBC News reported.

    Despite having a recommended national vaccine schedule, vaccination rates for American children have dropped during the pandemic.

    COVID cases are also declining among U.S. children, totally close to 28,000 last week, according to the American Academy of Pediatrics. It is the first time since early April that cases were under 30,000.

    An advantage to having COVID-19 shots on the vaccine schedule is that insurance providers typically will cover recommended vaccines. Though federal dollars are still paying for those vaccines, that will eventually end, NBC News reported.

    The COVID vaccines could also become a part of the federal Vaccines for Children program, which would provide them free to children covered by Medicaid.

    “By adding it to the VFC program, it now makes these vaccines available to these uninsured and underinsured children,” said Dr. Julie Morita, executive vice president of the Robert Wood Johnson Foundation, former public health commissioner for Chicago and a former practicing pediatrician.

    Morita called the schedule the “gold standard” for clinicians.

    “I used to look every year, waiting for this vaccine schedule, to make sure I was following the best vaccination guidance available,” Morita told NBC News.

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  • It’s Gotten Awkward to Wear a Mask

    It’s Gotten Awkward to Wear a Mask

    Last week, just a couple of hours into a house-sitting stint in Massachusetts for my cousin and his wife, I received from them a flummoxed text: “Dude,” it read. “We are the only people in masks.” Upon arriving at the airport, and then boarding their flight, they’d been shocked to find themselves virtually alone in wearing masks of any kind. On another trip they’d taken to Hawaii in July, they told me, long after coverings became optional on planes, some 80 percent of people on their flight had been masking up. This time, though? “We are like the odd man out.”

    Being outside of the current norm “does not bother us,” my cousin’s wife said in another text, despite stares from some of the other passengers. But the about-face my cousin and his wife identified does mark a new phase of the pandemic, even if it’s one that has long been playing out in fits and starts. Months after the vanishing of most masking mandates, mask wearing has been relegated to a sharply shrinking sector of society. It has become, once again, a peculiar thing to do.

    If you notice, no one’s wearing masks,” President Joe Biden declared last month on 60 Minutes. That’s an overstatement, but not by much: According to the COVID States Project, a large-scale national survey on pandemic-mitigation behaviors, the masking rate among Americans bounced between around 50 and 80 percent over the first two years of the pandemic. But since this past winter, it’s been in a slide; the project’s most recent data, collected in September, found that just 29 percent have been wearing masks outside the home. This trend may be long-standing on the population level, but for individuals—and particularly for those who still wear masks, such as my cousin and his wife—it can lead to moments of abrupt self-consciousness. “It feels like it’s something that now needs an explanation,” Fiona Lowenstein, a journalist and COVID long-hauler based in Los Angeles, told me. “It’s like showing up in a weird hat, and you have to explain why you’re wearing it.”

    Now that most Americans can access COVID vaccines and treatments that slash the risk of severe disease and death, plenty of people have made informed decisions to relax on masking—and feel totally at ease with their behavior while paying others’ little mind. Some are no longer masking all the time but will do so if it makes others feel more comfortable; others are still navigating new patterns, trying to stay flexible amid fluctuating risk. Saskia Popescu, an infectious-disease epidemiologist at George Mason University, told me that she’s now more likely to doff her mask while dining or working out indoors, but that she leaves it on when she travels. And when she does decide to cover up, she said, she’s “definitely felt like more of an outlier.”

    For some, like my cousin and his wife, that shift feels slightly jarring. For others, though, it feels more momentous. High-filtration masks are one of the few measures that can reliably tamp down on infection and transmission across populations, and they’re still embraced by many parents of newborns too young for vaccines, by people who are immunocompromised and those who care for them, and by those who want to minimize their risk of developing long COVID, which can’t be staved off by vaccines and treatments alone. Theresa Chapple-McGruder, the public-health director for Oak Park, Illinois, plans to keep her family masking at least until her baby son is old enough to receive his first COVID shots. In the meantime, though, they’ve certainly been feeling the pressure to conform. “People often tell me, ‘It’s okay, you can take your mask off here,’” Chapple-McGruder told me; teachers at the local elementary school have said similar things to her young daughters. Meghan McCoy, a former doctor in New Hampshire who takes immunosuppressive medications for psoriatic arthritis and has ME/CFS, has also been feeling “the pressure to take the mask off,” she told me—at her kid’s Girl Scout troop meetings, during trips to the eye doctor. “You can feel when you’re the only one doing something,” McCoy said. “It’s noticeable.”

    For Chapple-McGruder, McCoy, and plenty of others, the gradual decline in masking creates new challenges. For one thing, the rarer the practice, the tougher it is for still-masking individuals to minimize their exposures. “One-way masking is a lot less effective,” says Gabriel San Emeterio, a social worker at Hunter College who is living with HIV and ME/CFS. And the less common masking gets, the more conspicuous it becomes. “If most people met me, they wouldn’t know I was immunocompromised,” McCoy told me. “There’s no big sign on our foreheads that says ‘this person doesn’t have a functioning immune system.’” But now, she said, “masks have kind of become that sign.”

    Aparna Nair, a historian and disability scholar at the University of Oklahoma who has epilepsy, told me that she thinks masks are becoming somewhat analogous to wheelchairs, prosthetics, hearing aids, and her own seizure-alert dog, Charlie: visible tools and technologies that invite compassion, but also skepticism, condescension, and invasive questions. During a recent rideshare, she told me, her driver started ranting that her mask was unnecessary and ineffective—just part of a “conspiracy.” His tone was so angry, Nair said, that she began to be afraid. She tried to make him understand her situation: I’ve been chronically ill for three decades; I’d rather not fall sick; better to be safe than sorry. But she said that her driver seemed unswayed and continued to mutter furiously under his breath for the duration of the ride. Situations of that kind—where she has to litigate her right to wear a mask—have been getting more common, Nair told me.

    Masking has been weighed down with symbolic meaning since the start of the pandemic, with some calling it a sign of weakness and others a vehicle for state control. Americans have been violently attacked for wearing masks and also for not wearing them. But for a long time, these tensions were set against the backdrop of majority masking nationwide. Local mask mandates were in place, and most scientific experts wore and championed them in public. With many of those infrastructural supports and signals now gone, masking has rapidly become a minority behavior—and people who are still masking told me that that inversion only makes the tension worse.

    San Emeterio, who wears a vented respirator when they travel, recently experienced a round of heckling from a group of men at an airport, who started to stare, laugh, and point. Oh my god, look at what he’s wearing, San Emeterio recalls the strangers saying. “They clearly meant for me to hear it,” San Emeterio told me. “It didn’t make me feel great.” Alex Mawdsley, the 14-year-old son of an immunocompromised physician in Chicago, is one of just a handful of kids at his middle school who are still masking up. Since the start of the academic year, he’s been getting flak from several of his classmates “at least once a week,” he told me: “They’re like ‘You’re not gonna get COVID from me’ and ‘Why are you still wearing that? You don’t need it anymore.’”

    Alex’s mother, Emily Landon, told me she’s been shaken by the gawks and leers she now receives for masking. Even prior to the pandemic, and before she was diagnosed with rheumatoid arthritis and began taking immunosuppressive drugs, she considered herself something of a hygiene stan; she always took care to step back from the sneezy and sniffy, and to wipe down tray tables on planes. “And it was never a big deal,” she said.

    It hasn’t helped that the donning of masks has been repeatedly linked to chaos and crisis—and their removal, to triumph. Early messaging about vaccines strongly implied that the casting away of masks could be a kind of post-immunization reward. In February, CDC Director Rochelle Walensky described masks as “the scarlet letter of this pandemic.” Two months later, when the administration lifted its requirements for masking on public transportation, passengers on planes ripped off their coverings mid-flight and cheered.

    To reclaim a mask-free version of “normalcy,” then, may seem like reverting to a past that was safer, more peaceful. The past few years “have been mentally and emotionally exhausting,” Linda Tropp, a social psychologist at the University of Massachusetts at Amherst, told me. Discarding masks may feel like jettisoning a bad memory, whereas clinging to them reminds people of an experience they desperately want to leave behind. For some members of the maskless majority, feeling like “the normal ones” again could even serve to legitimize insulting, dismissive, or aggressive behavior toward others, says Markus Kemmelmeier, a social psychologist at the University of Nevada at Reno.

    It’s unclear how the masking discourse might evolve from here. Kemmelmeier told me he’s optimistic that the vitriol will fade as people settle into a new chapter of their coexistence with COVID. Many others, though, aren’t so hopeful, given the way the situation has unfolded thus far. “There’s this feeling of being left behind while everyone else moves on,” Lowenstein, the Los Angeles journalist and long-hauler, told me. Lowenstein and others are now missing out on opportunities, they told me, that others are easily reintegrating back into their lives: social gatherings, doctor’s appointments, trips to visit family they haven’t seen in months or more than a year. “I’d feel like I could go on longer this way,” Lowenstein said, if more of society were in it together.

    Americans’ fraught relationship with masks “didn’t have to be like this,” Tropp told me—perhaps if the country had avoided politicizing the practice early on, perhaps if there had been more emphasis on collective acts of good. Other parts of the world, certainly, have weathered shifting masking norms with less strife. A couple of weeks ago, my mother got in touch with me from one such place: Taiwan, where she grew up. Masking was still quite common in public spaces, she told me in a text message, even where it wasn’t mandated. When I asked her why, she seemed almost surprised: Why not?

    Katherine J. Wu

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  • The Masks We’ll Wear in the Next Pandemic

    The Masks We’ll Wear in the Next Pandemic

    On one level, the world’s response to the coronavirus pandemic over the past two and half years was a major triumph for modern medicine. We developed COVID vaccines faster than we’d developed any vaccine in history, and began administering them just a year after the virus first infected humans. The vaccines turned out to work better than top public-health officials had dared hope. In tandem with antiviral treatments, they’ve drastically reduced the virus’s toll of severe illness and death, and helped hundreds of millions of Americans resume something approximating pre-pandemic life.

    And yet on another level, the pandemic has demonstrated the inadequacy of such pharmaceutical interventions. In the time it took vaccines to arrive, more than 300,000 people died of COVID-19 in America alone. Even since, waning immunity and the semi-regular emergence of new variants have made for an uneasy détente. Another 700,000 Americans have died over that period, vaccines and antivirals notwithstanding.

    For some pandemic-prevention experts, the takeaway here is that pharmaceutical interventions alone simply won’t cut it. Though shots and drugs may be essential to softening a virus’s blow once it arrives, they are by nature reactive rather than preventive. To guard against future pandemics, what we should focus on, some experts say, is attacking viruses where they’re most vulnerable, before pharmaceutical interventions are even necessary. Specifically, they argue, we should be focusing on the air we breathe. “We’ve dealt with a lot of variants, we’ve dealt with a lot of strains, we’ve dealt with other respiratory pathogens in the past,” Abraar Karan, an infectious-disease physician and global-health expert at Stanford, told me. “The one thing that’s stayed consistent is the route of transmission.” The most fearsome pandemics are airborne.

    Numerous overlapping efforts are under way to stave off future outbreaks by improving air quality. Many scientists have long advocated for overhauling the way we ventilate indoor spaces, which has the potential to transform our air in much the same way that the advent of sewer systems transformed our water. Some researchers are similarly enthusiastic about the promise of germicidal lighting. Retrofitting a nation’s worth of buildings with superior ventilation systems or germicidal lighting is likely a long-term mission, though, requiring large-scale institutional buy-in and probably a considerable amount of government funding. Meanwhile, a more niche subgroup has zeroed in on what is, at least in theory, a somewhat simpler undertaking: designing the perfect mask.

    Two and a half years into this pandemic, it’s hard to believe that the masks widely available to us today are pretty much the same masks that were available to us in January 2020. N95s, the gold standard as far as the average person is concerned, are quite good: They filter out at least 95 percent of .3-micron particles—hence N95—and are generally the masks of preference in hospitals. And yet, anyone who has worn one over the past two and a half years will know that, lucky as we are to have them, they are not the most comfortable. At a certain point, they start to hurt your ears or your nose or your whole face. When you finally unmask after a lengthy flight, you’re liable to look like a raccoon. Most existing N95s are not reusable, and although each individual mask is pretty cheap, the costs can add up over time. They impede communication, preventing people from seeing the wearer’s facial expressions or reading their lips. And because they require fit-testing, the efficacy for the average wearer probably falls well short of the advertised 95 percent. In 2009, the federal government published a report with 28 recommendations to improve masks for health-care workers. Few seem to have been taken.

    These shortcomings are part of what has made efforts to get people to wear masks an uphill battle. What’s more,Over the course of the pandemic, several new companies have submitted new mask designs to NIOSH, the federal agency tasked with certifying and regulating masks,. Few, if any, have so far been certified. The agency appears to be overworked and underfunded. In addition, Joe and Kim Rosenberg, who in the early stages of the pandemic launched a mask company that applied unsuccessfully for NIOSH approval, told me the certification process is somewhat circular: A successful application requires huge amounts of capital, which in turn require huge amounts of investment, but investors generally like to see data showing that the masks work as advertised in, say, a hospital, and masks cannot be tested in a hospital without prior NIOSH approval. (NIOSH did not respond to a request for comment.)

    New products aside, there do already exist masks that outperform standard N95s in one way or another. Elastomeric respirators are reusable masks that you outfit with replaceable filters. Depending on the filter you use, the mask can be as effective as an N95 or even more so. When equipped with HEPA-quality filters, elastomerics filter out 99.97 percent of particles. And they come in both half-facepiece versions (which cover the nose and mouth) and full-facepiece versions (which also cover the eyes). Another option are PAPRs, or powered air-purifying respirators—hooded, battery-powered masks that cover the wearer’s entire head and constantly blow HEPA-filtered air for the wearer to breathe.

    Given the challenges of persuading many Americans to wear even flimsy surgical masks during the past couple of years, though, the issues with these superior masks—the current models, at least—are probably disqualifying as far as widespread adoption would go in future outbreaks. Elastomerics generally are bulky, expensive, limit range of motion, obscure the mouth, and require fit testing to ensure efficacy. PAPRs have a transparent facepiece and in many cases don’t require fit testing, but they’re also bulky, currently cost more than $1,000 each, and, because they’re battery-powered, can be quite noisy. Neither, let me assure you, is the sort of thing you’d want to wear to the movie theater.

    The people who seem most fixated on improving masks are a hodgepodge of biologists, biosecurity experts, and others whose chief concern is not another COVID-like pandemic but something even more terrifying: a deliberate act of bioterrorism. In the apocalyptic scenarios that most worry them—which, to be clear, are speculative—bioterrorists release at least one highly transmissible pathogen with a lethality in the range of, say, 40 to 70 percent. (COVID’s is about 1 percent.) Because this would be a novel virus, we wouldn’t yet have vaccines or antivirals. The only way to avoid complete societal collapse would be to supply essential workers with PPE that they can be confident will provide infallible protection against infection—so-called perfect PPE. In such a scenario, N95s would be insufficient, Kevin Esvelt, an evolutionary biologist at MIT, told me: “70-percent-lethality virus, 95 percent protection—wouldn’t exactly fill me with confidence.”

    Existing masks that use HEPA filters may well be sufficiently protective in this worst-case scenario, but not even that is a given, Esvelt told me. Vaishnav Sunil, who runs the PPE project at Esvelt’s lab, thinks that PAPRs show the most promise, because they do not require fit testing. At the moment, the MIT team is surveying existing products to determine how to proceed. Their goal, ultimately, is to ensure that the country can distribute completely protective masks to every essential worker, which is firstly a problem of design and secondly a problem of logistics. The mask Esvelt’s team is looking for might already be out there, just selling for too high a price, in which case they’ll concentrate on bringing that price down. Or they might need to design something from scratch, in which case, at least initially, their work will mainly consist of new research. More likely, Sunil told me, they’ll identify the best available product and make modest adjustments to improve comfort, breathability, useability, and efficacy.

    Esvelt’s team is far from the only group exploring masking’s future. Last year, the federal government began soliciting submissions for a mask-design competition intended to spur technological development. The results were nothing if not creative: Among the 10 winning prototypes selected in the competition’s first phase were a semi-transparent mask, an origami mask, and a mask for babies with a pacifier on the inside.

    In the end, the questions of how much we should invest in improving masks and how we should actually improve them boil down to a deeper question about which possible future pandemic concerns you most. If your answer is a bioengineered attack, then naturally you’ll commit significant resources to perfecting efficacy and improving masks more generally, given that, in such a pandemic, masks may well be the only thing that can save us. If your answer is SARS-CoV-3, then you might worry less about efficacy and spend proportionally more on vaccines and antivirals. This is not a cheery choice to make. But it is an important one as we inch our way out of our current pandemic and toward whatever waits for us down the road.

    For the elderly and immunocompromised, super-effective masks could be useful even outside a worst-case scenario. But more traditional public-health experts, who don’t put as much stock in the possibility of a highly lethal, deliberate pandemic, are less concerned about perfecting efficacy for the general public. The greater gains, they say, will come not from marginally improving the efficacy of existing highly effective masks but from getting more people to wear highly effective masks in the first place. “It’s important to make masks easier for people to use, more comfortable and more effective,” Linsey Marr, an environmental engineer at Virginia Tech, told me. It wouldn’t hurt to make them a little more fashionable either, she said. Also important is reusability, Jassi Pannu, a fellow at the Johns Hopkins Center for Health Security, told me, because in a pandemic stockpiles of single-use products will almost always run out.

    Stanford’s Karan envisions a world in which everyone in the country has their own elastomeric respirator—not, in most cases, for everyday use, but available when necessary. Rather than constantly replenishing your stock of reusable masks, you would simply swap out the filters in your elastomeric (or perhaps it will be a PAPR) every so often. The mask would be transparent, so that a friend could see your smile, and relatively comfortable, so that you could wear it all day without it cutting into your nose or pulling on your ears. When you came home at night, you would spend a few minutes disinfecting it.

    Karan’s vision might be a distant one. America’s tensions over masking throughout the pandemic give little reason to hope for any unified or universal uptake in future catastrophes. And even if that happened, everyone I spoke with agrees that masks alone are not a solution. They’re almost certainly the smallest part of the effort to ensure that the air we breathe is clean, to change the physical world to stop viral transmission before it happens. Even so, making and distributing millions of masks is almost certainly easier than installing superior ventilation systems or germicidal lighting in buildings across the country. Masks, if nothing else, are the low-hanging fruit. “We can deal with dirty water, and we can deal with cleaning surfaces,” Karan told me. “But when it comes to cleaning the air, we’re very, very far behind.”

    Jacob Stern

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