Tag: COVID patients

Why Are We Still Flu-ifying COVID?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Katherine J. Wu

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February 28, 2024
Is the Worst of Winter Over for COVID?

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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.”

Read: How worried should we be about XBB.1.5?

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.

Read: The worst pediatric-care crisis in decades

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.

Read: Should everyone be masking again?

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.

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Katherine J. Wu

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January 25, 2023
COVID Antibody Treatments Are in Decline

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

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

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

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

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

Read: Paxlovid mouth is real—and gross

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

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

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

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

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

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

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

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

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

Read: It’s gotten awkward to wear a mask

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

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

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Katherine J. Wu

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October 29, 2022