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I am on a mission to preserve the most valuable item in my home: my fiancé, who has never had COVID. Through sheer luck and a healthy dose of terror, he made it through the first pandemic year without getting sick. Shielded by the J&J vaccine and a Moderna booster, he dodged infection when I fell ill last November and coughed up the coronavirus all over our cramped New York City apartment. Somehow, he ducked the Omicron wave over the winter, when it seemed as though everyone was getting sick. And in the past few months, he has emerged unscathed from crowded weddings, indoor dinners, and flights across the country.

At this point, I worry about how much longer it’s going to last. People like him—I think of them as “COVID virgins”—are becoming a rare breed. Just yesterday, President Joe Biden thinned their ranks by one more person. The Institute of Health Metrics and Evaluation suggests that as of earlier this month, 82 percent of Americans have been infected with the coronavirus at least once. Some of those people might still think they’re never had the virus: Asymptomatic infections happen, and mild symptoms are sometimes brushed off as allergies or a cold. Now that we’re battling BA.5, the most contagious and vaccine-dodging Omicron offshoot yet, many people are facing their second, third, or even fourth infections. That reality can make it feel like the stragglers who have evaded infection for two and a half years are destined to fall sick sooner rather than later. At this point, are COVID virgins nothing more than sitting ducks?

Read: Of course Biden has COVID

The basic math admittedly doesn’t look promising. Most of the people getting infected right now seem to be coming down with the illness for the first time, even though they are a distinct minority. Nationally, we don’t have good data on who is getting COVID, though in New York, first infections seem to be  happening at five times the rate of reinfections. Part of why those who haven’t gotten COVID seem to be at a higher risk of infection is that taking into account all other factors—vaccination, age, behaviors—they lack the immunity bump conferred by a bout with the virus, no matter how fleeting that bump may be. On its own, this would suggest that these people are in fact sitting ducks who can’t avoid infection short of hunkering down in total isolation.

The experts I talked with agreed that the risk of infection is currently high. “We are finding now that with the more transmissible variants, it’s becoming more and more difficult to avoid infections,” Robert Kim-Farley, an epidemiologist at UCLA, told me. “However, it’s not inevitable.” Rick Bright, the CEO of the Rockefeller Foundation’s Pandemic Prevention Institute, was less certain. “Honestly, it might be inevitable, the way the virus has continued to change,” he said.

Still, they reiterated that we still don’t quite know just how at risk those who haven’t had COVID are—especially when BA.5 seems to be reinfecting so many people. “I don’t know if I would call them sitting ducks, necessarily,” Bright said, “but I would say every one of us is more vulnerable.” The unvaccinated are still the most vulnerable by far, especially to more severe outcomes. But even this far into the pandemic, it’s hard to know exactly why some vaccinated and boosted people have gotten sick while others haven’t—good pandemic behaviors might come into play, along with luck. Scientists are still investigating the role of other factors, including whether genetics might be protecting the immune systems of people who haven’t gotten COVID.

Read: Is BA.5 the ‘reinfection wave’?

Nevertheless, all of the experts argued that COVID virgins should still try to avoid infection. Above all, they should get up-to-date on vaccination and boosters. Once those layers of protection are in place, they should continue to be prudent—especially in crowded, indoor settings—but unless they are medically vulnerable, they don’t have to take more precautions than anyone else, Kim-Farley said.

The guidance for this group is the same as it is for everybody else largely because immunity by infection is protective, but only to an extent. BA.5, for one, seems to be able to reinfect people who were previously sick, sometimes even those who just a few months ago had an earlier version of Omicron. At this point, an infection from a year ago, let alone two, might not mean much immunologically. “People shouldn’t rely on prior infection, because it just is not as effective as prior vaccination,” Kim-Farley said. And though “hybrid immunity”—which results when a person gets sick and is then vaccinated, or vice versa—is thought to confer a good amount of protection, “that kind of assertion may be challenged” now that so many reinfections are occurring, the Yale epidemiologist Albert Ko told me.

The ultimate problem with people viewing themselves as sitting ducks is that this is the exact attitude epidemiologists do not want us to have. It can foster a “why bother?” demeanor, negating all public-health efforts to stop transmission and discouraging personal efforts to protect oneself. In other words, it promotes COVID fatalism, which is appealing because it offers relief from the daily anxiety and behavioral compromises of pandemic life by assuming that an infection is a question of when, not if. This notion can be liberating for those who have never gotten infected—and presumably it is part of the reason so few are left: Many people have already adopted a “meh” attitude toward COVID, not letting the fear of an infection get in the way of living their lives.

Even this late in the game, you should really try to avoid getting COVID if you can. Having to take precautions can be frustrating after so many months of pandemic life, but getting sick can be extremely unpleasant, even if you are vaccinated and boosted. There’s the risk of long COVID, yes, but those who escape it can still feel terrible for several days, if not weeks, Bright said. These infections don’t usually lead to hospitalization or death, but they’re no walk in the park either, especially for the elderly and the immunocompromised. And as COVID continues to mutate, you definitely want to forestall a second infection, or a third down the line. The consequences of repeated infections and their potential to cause long COVID or other health issues are not yet known. And, of course, the tenets of COVID 101 are still true: Even if your infection is mild, you can still spread it to someone who could have it much worse.

The grim reality is that as long as the virus shows no signs of abating, the number of COVID virgins will continue to shrink. Grappling with this reality will be a lot less stressful if we reframe the way we talk about getting COVID. Instead of fretting about the virus as something that could come for you, focus on what to do when it does. Those who are vaccinated and boosted may still be ducks sitting in the crosshairs of infection, but in all likelihood they won’t die or get severely ill, especially if they are young and healthy. “That’s what we care most about,” Ko said. The people who haven’t gotten sick should remember that they have already won—vaccines, in tandem with the treatments that are now available, mean that it’s far better to get sick now than it was a year or two ago.

When I told my fiancé that he would probably get COVID but should definitely still try not to get COVID, he described the situation as “Kafkaesque.” Indeed, these are absurd and illogical times. But at the very least, focusing on what is within our control can help us regain a modicum of sense. Short of total isolation, people may not be able to do much to avoid the coronavirus forever, but there’s still plenty they can do to escape the worst when it does come for them.

Last Christmas, as the Omicron variant was ricocheting around the United States, Mary Carrington unknowingly found herself at a superspreader event—an indoor party, packed with more than 20 people, at least one of whom ended up transmitting the virus to most of the gathering’s guests.

After two years of avoiding the coronavirus, Carrington felt sure that her time had come: She’d been holding her great-niece, who tested positive soon after, “and she was giving me kisses,” Carrington told me. But she never caught the bug. “And I just thought, Wow, I might really be resistant here.” She wasn’t thinking about immunity, which she had thanks to multiple doses of a COVID vaccine. Rather, perhaps via some inborn genetic quirk, her cells had found a way to naturally repel the pathogen’s assaults instead.

Carrington, of all people, understood what that would mean. An expert in immunogenetics at the National Cancer Institute, she was one of several scientists who, beginning in the 1990s, helped uncover a mutation that makes it impossible for most strains of HIV to enter human cells, rendering certain people essentially impervious to the pathogen’s effects. Maybe something analogous could be safeguarding some rare individuals from SARS-CoV-2 as well.

Read: America is running out of ‘COVID virgins’

The idea of coronaviral resistance is beguiling enough that scientists around the world are now scouring people’s genomes for any hint that it exists. If it does, they could use that knowledge to understand whom the virus most affects, or leverage it to develop better COVID-taming drugs. For individuals who have yet to catch the contagion—a fast-dwindling proportion of the population—resistance dangles “like a superpower” that people can’t help but think they must have, says Paula Cannon, a geneticist and virologist at the University of Southern California.

As with any superpower, though, bona fide resistance to SARS-CoV-2 infection would likely “be very rare,” says Helen Su, an immunologist at the National Institutes of Allergy and Infectious Disease. Carrington’s original hunch, for one, eventually proved wrong: She recently returned from a trip to Switzerland and found herself entwined with the virus at last. Like most people who remained unscathed until recently, Carrington had done so for two and a half years through a probable combination of vaccination, cautious behavior, socioeconomic privilege, and luck. It’s entirely possible that inborn coronavirus resistance may not even exist—or that it may come with such enormous costs that it’s not worth the protection it theoretically affords.

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Of the 1,400 or so viruses, bacteria, parasites, and fungi known to cause disease in humans, Jean-Laurent Casanova, a geneticist and an immunologist at Rockefeller University, is certain of only three that can be shut out by bodies with one-off genetic tweaks: HIV, norovirus, and a malaria parasite.

The HIV-blocking mutation is maybe the most famous. About three decades ago, researchers, Carrington among them, began looking into a small number of people who “we felt almost certainly had been exposed to the virus multiple times, and almost certainly should have been infected,” and yet had not, she told me. Their superpower was simple: They lacked functional copies of a gene called CCR5, which builds a cell-surface protein that HIV needs in order to hack its way into T cells, the virus’s preferred human prey. Just 1 percent of people of European descent harbor this mutation, called CCR5-Δ32, in two copies; in other populations, the trait is rarer still. Even so, researchers have leveraged its discovery to cook up a powerful class of antiretroviral drugs, and purged the virus from two people with the help of Δ32-based bone-marrow transplants—the closest that medicine has come to developing a functional HIV cure.

The stories with those two other pathogens are similar. Genetic errors in a gene called FUT2, which pastes sugars onto the outsides of gut cells, can render people resistant to norovirus; a genomic tweak erases a protein called Duffy from the walls of red blood cells, stopping Plasmodium vivax, one of several parasites that causes malaria, from wresting its way inside. The Duffy mutation, which affects a gene called DARC/ACKR1, is so common in parts of sub-Saharan Africa that those regions have driven rates of P. vivax infection way down.

In recent years, as genetic technologies have advanced, researchers have begun to investigate a handful of other infection-resistance mutations against other pathogens, among them hepatitis B virus and rotavirus. But the links are tough to definitively nail down, thanks to the number of people these sorts of studies must enroll, and to the thorniness of defining and detecting infection at all; the case with SARS-CoV-2 will likely be the same. For months, Casanova and a global team of collaborators have been in contact with thousands of people from around the world who believe they harbor resistance to the coronavirus in their genes. The best candidates have had intense exposures to the virus—say, via a symptomatic person in their home—and continuously tested negative for both the pathogen and immune responses to it. But respiratory transmission is often muddied by pure chance; the coronavirus can infiltrate people silently, and doesn’t always leave antibodies behind. (The team will be testing for less fickle T-cell responses as well.) People without clear-cut symptoms may not test at all, or may not test properly. And all on its own, the immune system can guard people against infection, especially in the period shortly after vaccination or illness. With HIV, a virus that causes chronic infections, lacks a vaccine, and spreads through clear-cut routes in concentrated social networks, “it was easier to identify those individuals” whom the virus had visited but not put down permanent roots within, says Ravindra Gupta, a virologist at the University of Cambridge. SARS-CoV-2 won’t afford science the same ease of study.

Read: Is BA.5 the ‘reinfection wave?’

A full analogue to the HIV, malaria, and norovirus stories may not be possible. Genuine resistance can manifest in only so many ways, and tends to be born out of mutations that block a pathogen’s ability to force its way into a cell, or xerox itself once it’s inside. CCR5, Duffy, and the sugars dropped by FUT2, for instance, all act as microbial landing pads; mutations rob the bugs of those perches. If an equivalent mutation exists to counteract SARS-CoV-2, it might logically be found in, say, ACE2, the receptor that the coronavirus needs in order to break into cells, or TMPRSS2, a scissors-like protein that, for at least some variants, speeds the invasive process along. Already, researchers have found that certain genetic variations can dial down ACE2’s presence on cells, or pump out junkier versions of TMPRSS2—hints that there could be tweaks that further strip away the molecules. But “ACE2 is very important” to blood-pressure regulation and the maintenance of lung-tissue health, said Su, of NIAID, who’s one of many scientists collaborating with Casanova to find SARS-CoV-2 resistance genes. A mutation that keeps the coronavirus out might very well “muck around with other aspects of a person’s physiology.” That could make the genetic tweak vanishingly rare, debilitating, or even, as Gupta put it, “not compatible with life.” People with the CCR5–Δ32 mutation, which halts HIV, “are basically completely normal,” Cannon told me, which means “HIV kind of messed up in ‘choosing’ CCR5.” The coronavirus, by contrast, has figured out how to exploit something vital to its host—an ingenious invasive move.

The superpowers of genetic resistance can have other forms of kryptonite. A few strains of HIV have figured out a way to skirt around CCR5, and glom on to another molecule, called CXCR4; against this version of the virus, even people with the Δ32 mutation are not safe. A similar situation has arisen with Plasmodium vivax, which “we do see in some Duffy-negative individuals,” suggesting that the parasite has found a back door, says Dyann Wirth, a malaria researcher at Harvard’s School of Public Health. Evolution is a powerful strategy—and with SARS-CoV-2 spewing out variants at such a blistering clip, “I wouldn’t necessarily expect resistance to be a checkmate move,” Cannon told me. BA.1, for instance, conjured mutations that made it less dependent on TMPRSS2 than Delta was.

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

Still, protection doesn’t have to be all or nothing to be a perk. Partial genetic resistance, too, can reshape someone’s course of disease. With HIV, researchers have pinpointed changes in groups of so-called HLA genes that, through their impact on assassin-like T cells, can ratchet down people’s risk of progressing to AIDS. And a whole menagerie of mutations that affect red-blood-cell function can mostly keep malaria-causing parasites at bay—though many of these changes come with “a huge human cost,” Wirth told me, saddling people with serious clotting disorders that can sometimes turn lethal themselves.

With COVID-19, too, researchers have started to home in on some trends. Casanova, at Rockefeller, is one of several scientists who has led efforts unveiling the importance of an alarm-like immune molecule called interferon in early control of infection. People who rapidly pump out gobs of the protein in the hours after infection often fare just fine against the virus. But those whose interferon responses are weak or laggy are more prone to getting seriously sick; the same goes for people whose bodies manufacture maladaptive antibodies that attack interferon as it passes messages between cells. Other factors could toggle the risk of severe disease up or down as well: cells’ ability to sense the virus early on; the amount of coordination between different branches of defense; the brakes the immune system puts on itself, so it does not put the host’s own tissues at risk. Casanova and his colleagues are also on the hunt for mutations that might alter people’s risk of developing long COVID and other coronaviral consequences. None of these searches will be easy. But they should be at least simpler than the one for resistance to infection, Casanova told me, because the outcomes they’re measuring—serious and chronic forms of disease—are that much more straightforward to detect.

If resistance doesn’t pan out, that doesn’t have to be a letdown. People don’t need total blockades to triumph over microbes—just a defense that’s good enough. And the protection we’re born with isn’t all the leverage we’ve got. Unlike genetics, immunity can be easily built, modified, and strengthened over time, particularly with the aid of vaccines. Those DIY defenses are probably what kept Carrington’s case of COVID down to “a mild course,” she told me. Immune protection is also a far surer bet than putting a wager on what we may or may not inherit at birth. Better to count on the protections we know we can cook up ourselves, now that the coronavirus is clearly with us for good.

When the original Omicron variant swept across the country this winter, it launched America into a new COVID era, one in which nearly everyone—95 percent of adults, according to one CDC estimate—has some immunity to the virus through vaccines, infection, or both. Since then, however, Omicron subvariants have still managed to cause big waves of infection. They’ve accomplished this by eroding our existing immunity.

This will keep happening. “There’s not a lot of things I’m confident about in SARS-CoV-2 evolution, but I think I’m extremely confident we’ll keep seeing new variants that are progressively eroding antibody neutralization,” says Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Center. Experts are cautiously optimistic that the pace of variant emergence will eventually slow, and for many people, reinfections are already milder and hospitals are not overwhelmed. But as the virus keeps changing, the only real guarantee is that it will be different—and that its changes won’t necessarily affect everyone uniformly.

SARS-CoV-2’s evolution follows a well-understood dynamic: When a variant sweeps around the world, it leaves behind a lot of immunity against itself. This puts intense evolutionary pressure on the virus to change things up; any subsequent variant has to somehow evade immunity to previous variants to keep finding new hosts. There are no limits to how long the coronavirus can keep doing this. Long-established respiratory viruses that cause the flu and common cold are still evolving to keep reinfecting us again and again.

But immune escape isn’t an intrinsic property of any new variant. SARS-CoV-2 is not ascending a ladder with each variant, becoming more and more immune escape-y over time. Rather, think of the coronavirus as an indefatigable rabbit being chased by our immune system, an equally indefatigable dog. The rabbit is always running away from the dog, and the dog is always trying to catch up to the rabbit. The space in which they have to chase each other is so big that it might as well be infinite on human timescales. As Bloom told me previously, the number of possible mutations in SARS-CoV-2 far, far exceeds the number of atoms in the known universe.

Read: You are going to get COVID again … and again … and again.

Occasionally, the rabbit might make a dramatic Omicron-like leap and shoot out ahead for a while until our immunity catches up. How often this will happen is difficult to predict. “It probably depends on how much of a black-swan event Omicron was,” says Adam Lauring, a virologist at the University of Michigan. Omicron was so different and so unusual compared with everything that had come before. “Could it happen again? Most people think probably not but … you don’t want to be burned twice.” Whether an Omicron-like event happens every two or 20 or 200 years can mean different trajectories for COVID’s future. But at this point, we have only two and a half years of data to go on, so prognosticate at your own risk.

More predictably, though, SARS-CoV-2 is likely to make smaller gains over time, accumulating mutations that make it incrementally better at reinfection. Virologists call this “antigenic evolution.” (Antigenic refers to the parts of a pathogen recognized by our immune system. For SARS-CoV-2, this is predominantly the spike protein.) Different viruses do seem capable of different rates of antigenic evolution. Of the four seasonal coronaviruses that cause common colds, for example, OC43 and 229E are evolving at a rate of 0.3 to 0.5 adaptive mutations in their spike proteins each year. But a third, NL63, doesn’t seem to be changing much at all, says Kathryn Kistler, a virologist also at Fred Hutch who has studied the evolution of the seasonal coronaviruses. She is currently trying to confirm this with blood-serum samples collected in the ’80s and ’90s. And there are so few samples of the fourth coronavirus, HKU1, that we don’t have enough to discern any trend.

Influenza is much better studied, and different types of flu also exhibit different rates of evolution from one another. Of the most common ones, influenza B is the slowest, roughly on par with the coronaviruses OC43 and 229E. H1N1 flu is faster, and H3N2, the predominant flu strain in the world right now, is the fastest. The differences may, at least in part, come down to the shape of the antigen that our immune system recognizes. The spike protein in coronaviruses, for example, needs to change enough so it fools the immune system, but not so much that it stops functioning altogether. H3N2 can get away with a smaller change in its spike-protein analogue: “It’s often one single mutation—sometimes two—[that] can give the virus a huge advantage,” Kistler told me.

Contrast that with measles, a virus that has barely evolved over decades. Our antibodies recognize multiple parts of its key protein. A recent study found that at least five out of eight key sites of that protein need to change at once to erode our immune defenses. A mutation in only one or two of these sites doesn’t confer much of an advantage, but gaining all five at once is very unlikely. So any potential new variants fizzle out, and the dominant measles variant stays quite stable.

Read: Is BA.5 the ‘reinfection wave’?

SARS-CoV-2, though, has been evolving antigenically faster than any of these viruses, even faster than H3N2. This could come down to the uniqueness of its spike protein, but some of this unusually fast pace over the past two years probably also has to do with the virus being novel. When a new strain of H1N1 “swine flu” hit in 2009, Kistler pointed out, it, too, had an initial burst before slowing down. The coronavirus’s Alpha and Delta variants emerged during a time with many immunologically naive people to infect, and the earliest variants mostly succeeded by becoming more intrinsically transmissible. The virus can only increase its transmissibility by so much, Bloom says, so SARS-CoV-2 is going to have less and less room to improve. However, it can keep finding new ways to get around immunity, as the Omicron subvariants have been doing.

The immunity landscape that SARS-CoV-2 is evolving against is also changing, though. Right now, some people have immunity against the original coronavirus or Alpha or Delta, others have immunity against the Omicron family, and yet others have both. As more variants emerge, our individual exposure history is going to be even more heterogeneous; depending on our previous immunity, some of us might be more susceptible than others to a new variant. The impact will be less uniform. We’ve already seen this with the Omicron subvariants, where countries with smaller previous waves are experiencing bigger BA.5 waves. Some people will also experience more waning immunity than others; older people, for example, tend to mount less durable immune responses to SARS-CoV-2, which is why this group is always prioritized for boosters. Aggressive vaccine updates and booster campaigns would help everyone’s immune system keep up.

Instead of always trying to catch up to the virus though, could we broaden our immunity and get ahead of it? Our current vaccines, while still very good at protecting against severe disease, are not capable of this. The White House is now promoting—though not really funding—next-generation vaccines that could potentially do better: pan-coronavirus vaccines that scientists hope will elicit antibodies against parts of the spike protein that do not change very much, or nasal vaccines to elicit antibodies in the nose and mouth where the virus first replicates, perhaps stopping an infection altogether.

But these ideas are not new to SARS-CoV-2—researchers have been trying these approaches to flu for many years. A universal flu vaccine is still elusive. A nasal flu vaccine, FluMist, does exist, but its effectiveness is quite mixed: It was originally thought to be more effective than the shot, then believed to be less effective—so much so that the CDC pulled the vaccine from 2016 to 2018—until it was reformulated. In any case, it’s clear that FluMist doesn’t come close to preventing all mild flu infections. Barring any major innovations in vaccine technology, our immune systems may be the dog chasing the coronavirus rabbit for a long time still.

When the monkeypox outbreak was first detected in the United States, it seemed, as far as infectious-disease epidemics go, like one this country should be able to handle. Tests and antivirals for the virus already existed; the government had stockpiled vaccines. Unlike SARS-CoV-2, monkeypox was a known entity, a relative softball on the pathogenic field. It wasn’t hypertransmissible, moving mainly through intimate contact during the disease’s symptomatic phase; previous epidemics had, with few interventions, rather quickly burned themselves out. The playbook was clear: Marshal U.S. resources and ensure they go to those most at risk, send aid abroad, and knock it out of the park. “If there was one virus that would lend itself to containment,” says Boghuma Kabisen Titanji, a virologist and infectious-disease physician at Emory University, this should have been it.

Two months later, global counts have crested above 21,000 confirmed cases, nearly a fourth of which are in the United States, which now ranks first among countries keeping track. Infections, most among men who have sex with men, have been documented in 46 states, D.C., and Puerto Rico; New York State and San Francisco have declared the outbreak a health emergency, as has the World Health Organization, on a global scale. Controlling the virus isn’t yet out of reach, says Jay Varma, the director of the Cornell Center for Pandemic Prevention and Response. But as the outbreak grows, so, too, does the challenge of combatting it. “It didn’t have to be this hard,” Varma told me.

Years of similar snafus surrounding SARS-CoV-2—a far, far more difficult virus to fight—should have taught the U.S. something about its own weak points. Instead, the lackluster response to monkeypox is making clear that the country’s capacity to deal with infectious disease may be even worse than it was at the start of 2020. Monkeypox, the country’s second infectious crisis in three years, isn’t just an unfortunate fumble. It’s confirmation that, although the U.S. might have once seemed like one of the nations best equipped to stop and prevent outbreaks, it is, in actuality, one of the best at squandering its potential instead.

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For years, the warning signs about monkeypox have been there. Decades of sporadic outbreaks in Central and West Africa had made the virus’s toll clear: It can cause a painful, debilitating sickness, with bouts of fevers and rashes, and in numerous cases leaves permanent scars behind; on occasion, certain strains of the pathogen can even kill. And though in many places the virus has infected indiscriminately, striking communities in close physical proximity to wildlife, a 2017 outbreak among young men in Nigeria hinted that sex could pose a particular risk.

So when case numbers began to erupt in several parts of Europe in May, indicating that the epidemic was already widespread, “it should have been obvious” that the epidemic had massive potential to expand, Varma told me. Multiple nations were already involved; the upcoming summer travel season posed a high risk. Infections were also concentrating in communities of men who have sex with men—networks that sexual-health experts know to be “dense, and where infectious diseases propagate very fast,” he said. And still, amid ringing alarm bells, the United States “underreacted,” Varma said, again and again.

Read: We should have seen monkeypox coming

Through much of May and June, monkeypox tests remained siloed within the CDC and its network of public-health labs, already stretched by the pandemic response. Health-care providers had to shuttle specimens to these centers for diagnosis, leaving patients on tenterhooks for days, even weeks, and delaying treatment, vaccination, and contact tracing. Even now, after testing capacity has climbed with the help of commercial labs, typical result turnaround times are stretching long. In Missouri, for instance, “they’re still telling us three to four days” at best, Hilary Reno, the medical director of the St. Louis County Sexual Health Clinic, told me.

Shots, too, have been troublingly scarce. America’s strategic national stockpile has millions of doses of smallpox vaccine (which also works against monkeypox), but most are ACAM2000, an inoculation that’s been linked to rare but serious side effects and shouldn’t be taken by certain vulnerable groups, including people living with HIV. Another shot, branded as Jynneos in the U.S., is safer, though, as a two-doser, may be trickier to administer post-exposure. Since spring, manufacturers of this shot have been turning the crank on assembly lines to bolster supply. But American officials hemmed and hawed for weeks before flying in much-needed doses from abroad, and then only in spurts.

The issue at hand certainly isn’t about vaccine demand. “Evey gay man I know is very ready for this vaccine and is willing to stand in line to get it,” says Steven Thrasher, a journalist and the author of The Viral Underclass, which examines the intersection of infectious disease and social inequality. Even though more vaccine doses are headed out, however, as cases balloon, the country still might not have enough. And with testing still strained, it won’t necessarily send doses to the right places. In Missouri, for instance, only a handful of cases has been reported so far, Reno told me. But with plenty of transmission likely going undetected, the state’s original order of shots might not cover its true needs. The country dawdled so long at the start line that even the relatively slow-moving monkeypox took its chance to race ahead—leaving the gap more and more difficult to close.

Early shortages in testing and care have also made the scope of the American outbreak difficult to estimate, or communicate—another parallel to the botched COVID response. A lack of tests means a lack of accurate numbers, which can make a devastating epidemic look deceptively contained. “That amplifies the cycle of neglect,” Varma told me, a pattern to which the U.S. has been particularly prone. Piling on to the problem is the ongoing dearth of funds for America’s sexual-health services, coincident with a recent rise in STIs. People with genital symptoms have struggled to reach providers, opening up even more cryptic channels for the virus to spread through.

Monkeypox is also a particularly challenging outbreak to be grappling with in the U.S., where sex is still a polarizing taboo, and men who have sex with men remain a marginalized community. And this is an especially charged time to be discussing the LGBTQ community in America, as the recent rolling back of abortion protections has stoked anxiety that other federal civil liberties may soon be on the chopping block. “We’re at this profoundly anti-gay, anti-trans moment,” Thrasher told me, at a time when those communities need more protection, not less.

Experts have praised some of the CDC’s efforts to avoid stigmatizing at-risk groups, which, at this juncture, remains essential. Monkeypox certainly doesn’t need sex to spread, Ina Park, a sexual-health expert at UC San Francisco, told me. Kissing, cuddling, and other situations that put bodies in close proximity for prolonged periods can also transmit the virus. So can contact with clothing or bed linens, because monkeypox can persist on unsanitized surfaces for days. Which does mean that men who have sex with men are definitely not the only ones in danger. At the same time, some people have been so fearful of casting monkeypox as an exclusively “gay disease” that sex has almost been censored from discussions, “giving people a misperception of the different risks that populations are facing right now,” Thrasher said. Especially while supplies remain so limited, we need to be “vaccinating people where the virus is moving.” Which means “we need to give both messages simultaneously,” Park said, “that this is not something that only affects gay men” while nodding to the fact that monkeypox is still “primarily affecting certain communities,” a trend that should influence the distribution of shots. Calls for the mass vaccination of “children or cis-het suburban moms,” Titanji told me, are “not where you’re going to get the most impact.”

Read: U.S. messaging on monkeypox is deeply flawed

To communities of men who have sex with men, how the Biden administration acts in this moment is revealing unspoken priorities and values. “In June, when it’s time to put rainbow flags up, they do,” says Keletso Makofane, an epidemiologist at Harvard’s School of Public Health, who’s been tracking the outbreak’s progression via an LGBTQ-community-led survey. “But when it’s time to give us resources? To prevent what some people describe as the worst pain they’ve ever felt in their lives? They choose not to.” Now, some experts are even bogged down in debates over whether monkeypox should be described as a sexually transmitted infection. But underlying the squabble is the far more important question of resource allocation, Makofane told me. This is “really a conversation about, Do these people deserve compassion and care?” Continuing to draw vital tools and resources away from at-risk populations, he said, would suggest the nation believes that the answer is no.

As long as the virus continues to move predominantly through networks of men who have sex with men, the U.S. still has the opportunity to swiftly intervene, track transmission, and dole out resources in a targeted way, Varma told me. But monkeypox’s current pattern may not hold. Already, the virus has begun to hop across genders and age groups, leveraging other, nonsexual forms of close contact. Infections in young children, who likely contracted the infection in their households, and among people incarcerated in prisons, where contagion is particularly difficult to quash, are starting to appear. And across geographies, familiar inequities in access to tests, vaccines, and treatments have begun to appear.

Monkeypox’s overlapping tenure with SARS-CoV-2 has aggravated matters as well. “This virus could not have picked a worse time to make its grand entrance to the global scene,” Titanji said. Still reeling from one outbreak, people are weary, and have “very little appetite for taking on another,” Thrasher told me. Numbed by COVID’s persistent toll, the public has also latched onto comforting comparisons that, although based in kernels of truth, have been warped into misleading extremes: Monkeypox might be less transmissible and less deadly than the coronavirus, but it is not an ignorable nuisance that’s guaranteed to dissipate. The larger the swath of society that’s affected, Titanji told me, the unwieldier the outbreak gets.

The top priority now, experts told me, should be funneling funds toward distributing vaccines and scaling up testing. Health workers and patients need continued guidance on the disease’s often-subtle symptoms and the possibility of silent transmission, as well as the resources to administer speedy care. Paid sick leave and housing support would also help ease the burden of monkeypox isolation, which, given the lengthy course of symptoms, can last for weeks. Should such efforts fall short, as they clearly have with SARS-CoV-2, monkeypox could become the second virus to set up permanent residence in the U.S. in the span of three years—giving it all the more opportunity to find new ways to spread, shape-shift, and propagate disease. Preventing that means acting decisively now, to make up for the time we’ve already lost.

Last week, students returning to campus at Oberlin College in Ohio got a shock: A local news outlet reported that the campus’ student health services would severely limit who could get contraception prescriptions. They would only be given to treat health problems — not for the purpose of preventing pregnancy — and emergency contraception would only be available to victims of sexual assault.

It turned out the college had outsourced its student health services to a Catholic health agency – and like other Catholic health institutions, it follows religious directives that prohibit contraception to prevent pregnancy. They also prohibit gender-affirming care.

“I would characterize the student’s reaction as outrage,” says Remsen Welsh, a fourth-year Oberlin student and co-director of the student-run Sexual Information Center on campus. “A lot of people in my circles were sending [the news story] around like, what is happening?”

Although the college quickly came up with a new plan to offer reproductive health services to students on campus, the incident at Oberlin shows the wide reach of Catholic health care in the U.S., and how the rules these institutions follow can limit access to contraception.

Now that many states – including Ohio – have adopted restrictions or outright bans on abortion, that’s also raised the stakes for contraception access.

Religious restrictions affect many health care settings

Issued by the U.S. Council of Catholic Bishops, the Ethical and Religious Directives that guide Catholic health care systems “prohibit a broad swath of reproductive care,” including birth control pills, IUDs, tubal ligation and vasectomies, says Dr. Debra Stulberg, a professor of family medicine at the University of Chicago who has researched how these directives play out in health care.

Catholic hospitals have long been a mainstay of health care in America. And these days, the directives apply to a wide range of settings where people seek reproductive health care – including urgent care centers, doctors’ offices and outpatient surgery centers that have been bought by or merged with Catholic health systems.

They can also apply when Catholic health agencies are hired to manage health care services for other institutions, which is what happened at Oberlin.

Four of the 10 largest health care systems in the country are Catholic, according to a 2020 report. In some counties, they dominate the market. In 52 communities, the report found, a Catholic hospital is the only one around within a 45-minute drive.

“After all this consolidation, this is where it shakes out, where we’ve got about 40% of reproductive age women living in areas with high or dominant Catholic hospital market share,” says Marian Jarlenski, a health policy researcher at the University of Pittsburgh, who examined the data in 2020.

‘Not transparent at all’

Patients often aren’t aware that these restrictions might affect the care they get, says Lois Uttley, a senior advisor with the health advocacy group Community Catalyst. They may not realize their hospital or doctor’s office has Catholic ties. For instance, Common Spirit Health, one of the nation’s biggest health systems, is Catholic, but you wouldn’t know it from its name. And Uttley says Catholic health institutions typically don’t publicize these policies.

“They are not open and transparent about it at all,” Uttley says. “We think it’s only fair that a patient be warned ahead of time about what she may or may not be able to get at a local doctor’s office or urgent care center or hospital.”

In a campus bulletin posted on Tuesday, Oberlin’s president, Carmen Twillie Ambar, said Oberlin had only recently learned that these restrictions would be enforced by Bon Secours, the large Catholic health system whose subsidiary was hired to run the college’s health services. Bon Secours told the local Chronicle-Telegram that it would only offer birth control prescriptions for medical reasons – an exception allowed under the religious directives.

When workarounds are all you’ve got

In practice, many doctors who work for Catholic-owned or affiliated health providers routinely rely on “medical condition” exceptions as a way to get around religious restrictions on contraception, Stulberg’s research has found.

For example, hormonal IUDs can be used to control heavy menstrual bleedings, so doctors will often say they’re providing the IUD to treat this condition, even if the real goal is contraception.

Or doctors who aren’t allowed to perform a tubal ligation might instead remove the tubes altogether — they’ll just say it’s to lower a patient’s risk of ovarian cancer. Dr. Corinne McLeod, an OB/GYN at Albany Medical Center, says these kinds of workarounds were pretty common when she worked at a Catholic hospital in Albany, N.Y.

“That was basically a wink, wink, nudge, nudge,” McLeod says, adding, “Everybody knew what was happening. That was just the way they got around [restrictions].” One problem with relying on such loopholes, she says, is that if religious higher-ups at institutions get wind of it, they might crack down.

In other cases, workarounds might include creating a separately funded and run wing within a Catholic hospital or health clinic to provide the full range of reproductive health services.

That’s essentially what happened at Oberlin: The college partnered with a local family planning clinic to offer these services on campus three days a week, and said it would provide students with transportation to the clinic on other days. But the Catholic health provider will continue to offer other health services on campus.

Tiffany Yuen, a fourth-year Oberlin student who runs the Sexual Information Center with Welsh, said the solution was “a start. But it’s not enough.” In the past, about 40% of visits to the student health center were related to sexual health, according to Aimee Holmes, a certified nurse midwife who worked as a women’s health specialist at Oberlin for many years until Bon Secours’ subsidiary took over.

‘In some cases, women truly have no other choices’

Research suggests that even with workarounds, Catholic directives can limit women’s contraception choices. For example, one study found that while it was pretty easy for patients to book an appointment for hormonal birth control at clinics owned by Catholic hospitals, it was rarer to get one if you wanted a copper IUD, which is one of the most effective forms of long-acting reversible contraception.

I personally ran into these limitations eight years ago, when I gave birth to my second child. When I asked my doctor for a tubal ligation once I was on the delivery table, he informed me he couldn’t do the procedure because we were at a Catholic hospital. A recent study suggests this experience is common: It found that women who deliver at a Catholic hospital are half as likely to get tubal ligation or removal as those who deliver at another type of hospital.

Stulberg has conducted surveys that find many people don’t realize their choices will be limited because they don’t know their health provider is governed by these rules. “And of the people that had some kind of a reproductive health refusal, the majority, it wasn’t until either they were there or afterwards that they found out that they couldn’t get what they wanted,” she says.

In some cases, patients may simply be able to go to another health provider to get the contraception they need – but not always. “In some cases, women truly have no other choices,” Stulberg says. “This hospital or this system is the only provider in town.”

She says a patient’s options may also be constrained depending on their health insurance and whether the providers covered under the plan are subject to religious directives.

Several experts said that these restrictions can often impact low-income patients disproportionately. Dr. Karishma Dara, a family medicine doctor in Seattle, says that when she worked as a resident at a Catholic hospital in Washington, D.C., that served many low-income people, patients who came in for IUD appointments were told they had to go to a different, non-Catholic clinic to get the devices inserted.

“Any time that you have to add another step to getting care or contraceptive care, it’s like another point at which an unintended pregnancy can happen,” Dara says.

In fact, Catholic directives can limit access to contraception long after a health care facility stops being Catholic, says Elizabeth Sepper, an expert on religious liberty and health law at the University of Texas at Austin. “There are lots of examples where a Catholic health system has purchased a hospital, just held it for a handful of years and then sold the hospital,” she says. “But the purchase agreement then commits the next owner to continue the Catholic religious restrictions.”

Reproductive rights advocates want to see laws that require hospital systems to be more transparent about what health services they do and don’t offer. Legislators in New York have introduced such a law.

“You know, I’m not against Catholic health care, but I think that patients need to know what kind of services are available to them,” says Jarlenski.

Four days after recovering from a COVID-19 infection, President Joe Biden has tested positive again. When he first got sick, Biden—like more than one-third of the Americans who have tested positive for COVID-19 this summer, according to the U.S. government’s public records—was prescribed Paxlovid, an antiviral pill treatment made by Pfizer. Like many Paxlovid takers, he soon tested negative and resumed his normal activities. And then, like many Paxlovid takers, his infection came right back. (Biden does not currently have symptoms, according to his physician.)

With more than 40,000 prescriptions being handed out a day, we’re taking Paxlovid at about the same rate that we’re taking oxycodone. When Biden got sick last week, he started taking the pills before the day was out. When Anthony Fauci had COVID in June, he took two courses. That enthusiasm is in line with the government’s messaging around the drug.

The Biden administration has consistently hailed Paxlovid as an effective tool in the fight against SARS-CoV-2. “For the most part, Paxlovid is doing what you’re asking it to do,” Fauci told me recently. Many researchers and physicians agree. Ann Woolley, the associate clinical director of transplant infectious diseases at Brigham and Women’s Hospital, told me that she feels “very fortunate” to be able to offer Paxlovid to her patients, even if it’s not a COVID panacea.

But some providers are prescribing the drug with a bit less enthusiasm, particularly when it comes to vaccinated patients (such as Biden and Fauci). Reshma Ramachandran, a family-medicine doctor and researcher at Yale, told me that she’s feeling a sense of “resignation” about Paxlovid. Though it’s one of the few COVID treatments she can offer, she can’t say with confidence that the pills will help someone who’s been immunized. Bob Wachter, the chair of medicine at UC San Francisco, called assessing the value of Paxlovid for these patients a “massively complicated three-dimensional chess game.” Anyone who might want to take the drug should discuss with their doctor whether and when they’ve been infected before, how many vaccine doses they’ve had (and when they had them), their age, and other risk factors—all in light of the limited clinical data that are now available. Patients will surely struggle to make sense of all these variables. Their doctors might, too. “I can barely decide whether I want it, and I do this for a living,” Wachter said.

A person could have easily forgiven such confusion when Paxlovid was first being rolled out on a large scale, following an emergency authorization last winter. But now, eight months later? More than 3 million people have taken it. Pfizer has announced two sets of results from its clinical trial and submitted data to the FDA for full approval. Dozens of independent studies of the drug have been published or released as preprints. And yet, doctors remain unsure of: who might benefit from Paxlovid and in what ways; who really needs it; why and how often rebound infections such as Biden’s and Fauci’s occur; whether the drug reduces patients’ risk of developing long COVID; and whether the virus will slowly develop resistance to the drug.

Read: Rebound COVID is just the start of Paxlovid’s mysteries

These questions remain unanswered (or incompletely answered) thanks to corporate secrecy, the minutiae of drug testing, and the necessary care with which human trials are conducted. But in a more fundamental way, the persistent fog around Paxlovid comes from the disease that it’s meant to alleviate. The pandemic is simply moving too quickly, the virus is evolving too fast, and our responses to it are changing too often for anyone to find unambiguous answers about one specific drug.

Before we walk into that fog, let’s get some things settled: Paxlovid is effective at keeping unvaccinated, high-risk people—those who are most likely to require hospitalization if they come down with COVID—alive and out of the hospital. The drug has some side effects, such as a strange and unpleasant taste, but its safety profile is stellar. (It does have some known, dangerous interactions with other common medications.) No one died while taking it in Pfizer’s clinical trials. Got it? Good. Now on to the mysteries.

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When I spoke with Fauci, he repeatedly emphasized that the point of Paxlovid is “to keep you out of the hospital and prevent you from progressing to severe disease.” But does the drug really have this benefit for young, vaccinated people, who would seem to represent a significant proportion of those taking it? COVID hospitalization rates for those younger than 60 are currently less than two per 100,000. Given those numbers, Paxlovid—or any other drug, for that matter—isn’t likely to provide much benefit. “If your risk of hospitalization is incredibly low, to make that even lower is somewhat improbable,” David Boulware, an infectious-disease physician and a researcher at the University of Minnesota, told me.

That might explain why Pfizer’s trial found no statistically significant effect on hospitalization among a group of unvaccinated people at low risk from the disease and vaccinated people at high risk. An Israeli study conducted this winter similarly showed that Paxlovid did not significantly affect hospitalization rates in vaccinated, high-risk patients younger than 65. A study from Hong Kong did find that vaccinated Paxlovid takers were only about two-thirds as likely as non-takers to be hospitalized; but these data were not broken down by age, and the most popular vaccine choice among older Hong Kongers, Sinovac, is less effective than the mRNA-based vaccines that have dominated in the United States. A study that Woolley co-authored in Massachusetts found that Paxlovid reduced the risk of hospitalization for vaccinated people of all ages by 28 percent; and if a person’s last shot was more than 20 weeks old, the protection offered by the pills nearly doubled.

With the exception of Pfizer’s clinical trial, these studies are not placebo-controlled experiments, which makes them vulnerable to confounding factors. Woolley acknowledged the limitations of her own research, and told me that the benefit she found was “incremental.” Still, thanks to the paper, “I do feel like I have, now, significant data and experience to be able to have a well-informed discussion with my patients,” she said. “I’m not worried that we are giving placebo.”

Read: Paxlovid mouth is real—and gross

Other experts aren’t yet convinced. “I think we’re still left with a little bit of head-scratching about the utility of the drug in younger people or in people who are fully vaccinated and boosted,” Wachter told me. Boulware said he’s eager to see Pfizer’s results separated by vaccination status, which the company has not released. Those numbers wouldn’t necessarily tell us how Paxlovid fares against BA.5, but at least they come from a placebo-controlled trial. The data that have been made public to this point, he said, “suggest that there’s really minimal to no benefit, most likely, for the vast majority of people.”

If Paxlovid was shown to have benefits beyond keeping people out of the hospital—if we knew that it made symptoms less intense, for example, or go away sooner—then the case for using it in young, vaccinated people might be stronger. But so far, those data have been lacking too. Pfizer’s own trials found that the drug did not reduce the duration of COVID patients’ symptoms or work to prevent infection when taken as a prophylactic.

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According to a CDC advisory, people who take Paxlovid for a COVID-19 bout could experience a resurgence of the infection—a Paxlovid rebound—between 2 and 8 days after their initial recovery. Biden’s four-day boomerang, then, is fairly typical.

How common are these rebounds, and why do they occur? Even now, no one really knows. The Biden administration and researchers have maintained that rebound cases are not severe in general. But no definitive evidence has emerged to indicate how often they occur, who’s most likely to get them, or whether they’re related to Paxlovid at all. “It remains one of the most confusing things I can recall during the pandemic,” Wachter said.

The few studies that have quantitatively assessed the rate of rebound have returned a range of numbers, centered at something less than 10 percent. Pfizer told me this spring that just 2 percent of their unvaccinated, high-risk Paxlovid takers rebounded during clinical trials. In June, a Mayo Clinic study of 483 patients logged a symptom-rebound rate of less than 1 percent, while one from Case Western Reserve University and the National Institutes of Health found that 5.4 percent of Paxlovid patients tested positive again within 30 days, and 5.9 percent had a recurrence of symptoms. (Similar numbers rebounded after taking molnupiravir.)

Yet some clinicians told me that they don’t yet buy these numbers. Wachter said he suspects the real rebound rate is more like 10 or 15 percent. Ramachandran’s experience with her patients, family, and friends makes her think it’s even higher, perhaps 25 or 50 percent. (She stressed that this estimate is purely based on anecdotes.) Woolley didn’t want to pick a number, but said that a rate higher than 2 percent and much lower than 20 seems plausible to her. Even Fauci was willing to entertain the notion that 2 percent simply isn’t right. “I want to be humble and modest enough to say I don’t know,” he said.

Daniel Griffin, an infectious-disease expert, believes that fewer than 10 percent of people who take Paxlovid end up rebounding, but he also thinks those rebounds have nothing to do with the drug. “We’ve always seen this,” he told me. According to Griffin, physicians who have been taking care of COVID patients since 2020 were already seeing a pattern of disease, especially in high-risk patients, that entailed two weeks of worsening symptoms. He suspects Paxlovid suppresses the first half of the illness; when that suppression stops, you get the “rebound.”

Some experts have hypothesized that the way we’re using Paxlovid may be causing rebound. Wachter raised the possibility that taking Paxlovid too early in your course of illness could be one factor. The idea is plausible, Woolley told me, but “it goes against what we know also to be the case: The earlier you treat with an antiviral, the more effective it is.” (The FDA has only authorized Paxlovid to be distributed within the first five days of a patient’s having COVID symptoms.)

Do rebound cases suggest that the virus can evolve, within a patient, to make itself Paxlovid-proof? Again, the research seems to point in two directions. A group of researchers at UC San Diego studied one rebound case very carefully, and ruled out antiviral resistance as the cause. But even if resistance isn’t driving rebound, subsequent research has shown that SARS-CoV-2 is capable of developing resistance to Paxlovid, at least in a lab setting. “Any time you’re treating a disease caused by an RNA virus with a single drug, it’s not optimal, just because their capacity for change is great,” Timothy Sheahan, a virologist at the University of North Carolina at Chapel Hill, told me. He described the way he studies antiviral resistance in the lab. Step one: Grow a virus. Step two: Add some antiviral medicine, but not enough to completely suppress viral replication. Step three: Introduce that virus to a new host. Repeat. It sure sounds a lot like a COVID patient taking Paxlovid, rebounding, not realizing that they’re contagious again, and giving the virus to somebody else.

To ward off the possibility of resistance, Sheahan said, we need other drugs. “My hope, taking a page from the HIV-therapy playbook, is that there will and should be a multidrug cocktail to treat this disease, at the very minimum containing a few direct-acting antivirals,” he said. He’s also keen to find out whether such a cocktail would eliminate rebound.

Other researchers, including the ones from UC San Diego, suspect that prescribing a longer Paxlovid course might do the trick. Pfizer is planning to test whether a 10- or 15-day course of the drug might lead to better results, including lower rebound rates, among immunocompromised patients.

“I think it’s really important to determine what the real duration of treatment should be,” Fauci told me. Maybe, he said, it’s “going to have an impact not only on rebound, but also on whether a person gets long COVID or not.” But Ramachandran and Wachter both said they fear that hypothetical connection could go both ways: Perhaps rebound could raise a person’s chances of getting long COVID. To be clear, there is no empirical evidence as yet that supports this possibility—just physicians’ feelings of uncertainty around Paxlovid, plus some anecdotes. A few months ago, Wachter’s wife had COVID, took Paxlovid, and rebounded. Now, he said, she gets tired much more easily than she did before.

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Don’t expect this fog to lift anytime soon. For one thing, Pfizer has not yet made full data on the use of Paxlovid by vaccinated people available to researchers or anyone else. The Biden administration has not made any public efforts to pressure the company into doing so.

More research groups are, of course, working to find answers. Several experts told me they’re eagerly awaiting the results of the RECOVERY trial in the U.K., which will rigorously test Paxlovid in hospitalized patients. Woolley and her colleagues plan to study the risk profiles of patients who request a second course of Paxlovid because they experience a rebound. At UNC, Sheahan is part of a group working on a rebound-related study. Fauci said, “We are making steps and planning studies and doing concept sheets for studies” regarding rebound rates and the appropriate duration of treatment.

All of that research is going to take time. A spokesperson for the RECOVERY trial told me that fewer than 100 participants had been recruited as of July 25, and that the researchers need “at least several thousand” to draw conclusions. “It is likely to be many months yet before the trial can generate a result for Paxlovid,” they wrote in an email. Pfizer’s trial in immunocompromised patients, which will specifically investigate rebound and treatment duration, is listed as “not yet recruiting” on clinicaltrials.gov. Sheahan and his colleagues began planning their study around the turn of the new year, and only received approval from their institutional research board this month. They haven’t yet begun enrolling participants. When I asked Sheahan when he expected results, he said, “Hopefully several months.”

By the time this work gets peer-reviewed and published, it will be a little out of date. Months from now, America’s immune landscape will be different thanks to new infections, waning immunity, and newly formulated vaccines. We might be facing a new variant or subvariant that causes more or less severe disease, or replicates differently in the body, or simply responds differently to antivirals. The pandemic has been in an accelerating state of all-over-the-place since last year; research on Paxlovid can only lag behind.

In the meantime, patients and providers are muddling through. All of the doctors I spoke with said that they’re still erring on the side of prescribing Paxlovid, thanks to its lack of debilitating side effects. Sheahan, though not a medical doctor, was recently a Paxlovid patient when he came down with COVID after traveling. “I ended up on the medication within 48 hours after the onset of symptoms and was antigen negative in nine days. And it never came back,” he said when we spoke last week. Five days later, he emailed me to say that he had tested positive again.

On the list of perfect pet parents, Mikel Delgado, a professional feline-behavior consultant, probably ranks high. The Ph.D. expert in animal cognition spends half an hour each evening playing with her three torbie cats, Ruby, Coriander, and Professor Scribbles. She’s trained them to take pills in gelatin capsules, just in case they eventually need meds. She even commissioned a screened-in backyard catio so that the girls can safely venture outside. Delgado would do anything for her cats—well, almost anything. “Guilty as charged,” Delgado told me. “I do not brush my cats’ teeth.”

To be fair, most cat owners don’t—probably because they’re well aware that it’s weird, if not downright terrifying, to stick one’s fingers inside an ornery cat’s mouth. Reliable stats are scarce, but informal surveys suggest that less than 5 percent of owners give their cats the dental scrub-a-dub-dub—an estimate that the vets I spoke with endorse. “I’m always very shocked if someone says they brush their cat’s teeth,” says Anson Tsugawa, a veterinary dentist in California. When Steve Valeika, a vet in North Carolina, suggests the practice to his clients, many of them “look at me like I’ve totally lost it,” he told me. (This is where I out myself as one of the loons: My cats, Calvin and Hobbes, get their teeth brushed thrice weekly.)

There certainly is an element of absurdity to all of this. Lions, after all, aren’t skulking the savannas for Oral-Bs. But our pets don’t share the diets and lifestyles of their wild counterparts, and their teeth are quite susceptible to the buildup of bacteria that can eventually invade the gums to trigger prolonged, painful disease. Studies suggest that most domestic cats older than four end up developing some sort of gum affliction; several experts told me that the rates of periodontal disease in household felines can exceed 80 percent. Left untreated, these ailments can cost a cat one or more teeth, or even spread their effects throughout the body, potentially compromising organs such as the kidneys, liver, and heart.

To stave off kitty gum disease, veterinary guidelines and professionals generally recommend that owners clean their cat’s chompers daily, ideally for at least a minute, hitting every tooth. “That’s the gold standard,” says Santiago Peralta, a veterinary dentist at Cornell University. Even a gap of two or three days can leave enough time for tartar to cement, Jeanne Perrone, a veterinary-dentistry trainer in Florida, told me. But brushing feline teeth is also really, really, really hard. Most cats aren’t keen on having things shoved into their mouth, especially not bristly, sludge-covered sticks. (Dogs don’t always love cleanings either, but they’re at least used to engaging their owners with their mouths.) My old cat, Luna, was once so desperate to escape a brushing that she shrieked in my face, then peed all over the floor.

Read: Why we think cats are psychopaths

A niche industry has sprouted to ease the ordeal for hygiene-conscious humans: poultry-flavored toothpastes, cat-size toothbrushes, silicone scrubbers that fit on fingers. Sometimes the gear helps; when Chin-Sun Lee, a New Orleans–based writer, purchased malt-flavored toothpaste for her cat, Tuesday, he went bonkers for the stuff. Every morning, he comes trotting over just so he can lick the brush. Krissy Lyon, a neuroscientist at the Salk Institute, told me that one of her cats, Cocchi, is so crazy for his toothpaste that she and her partner have to “restrain him or lock him in a different room” while they’re brushing the teeth of their other cat, Noma.

But tasty toothpaste isn’t a sufficient lure for all. Valeika, who extols the virtues of feline oral health, admitted that even his own cat, Boocat, doesn’t reap the benefits of his brushing expertise. He “tried hard-core for a couple weeks” when he adopted her seven years ago. But Boocat was too feisty to stand for such a thing. “She can be a real terror,” Valeika told me. “We once saw her chase a bear out of our yard.”

Maybe Boocat is picking up on how odd the whole toothbrushing ritual can be. Even most American people weren’t regularly scrubbing their dentition until around the time of World War II. Vet dentistry, which borrowed principles from its human analogue, “is a relatively new discipline,” Peralta told me. “Thirty years ago, nobody was even thinking about dog or cat teeth.” Nor was it all that long ago that people across the country routinely let their pets sleep outside, eat only table scraps, and run hog wild through the streets. Now pets have become overly pampered, their accessories Gooped. Experts told me that they’ve seen all kinds of snake-oil hacks that purport to functionally replace feline toothbrushing—sprays, gels, toys, water additives, even calls to rub cat teeth with coconut oil. A lot of these products end up just cosmetically whitening teeth, temporarily freshening breath, or accomplishing nothing at all. If a super-simple, once-a-month magic bullet for dental hygiene existed, Tsugawa told me, “we’d be doing it for our own teeth.”

There are probably a lot of un-toothbrushed cats out there who could be s-l-o-w-l-y taught to accept the process and maybe even enjoy it. Mary Berg, the president of Beyond the Crown Veterinary Education, told me that one of her colleagues trained her pet to relish the process so much that “she could just say ‘Brusha brusha brusha’ and the cat would come running.” But getting to that point can require weeks or months of conditioning. Berg recommends taking it day by day, introducing cats first to the toothpaste, then to getting one or two teeth touched, and on and on until they’re comfy with the whole set—always “with lots of praise and reward afterward,” she said. And that’s all before “you introduce that scary plastic thing.”

Read: An offbeat approach to bonding with cats

That’s a big ask for many owners, especially those who went the cat route because of the creatures’ rep for being low-maintenance. The consequences of skipping toothbrushing are also subtle because they don’t directly affect humans, Delgado told me. Miss a nail trimming, and the couch might pay the price. But cat teeth aren’t often glimpsed.

The potential downsides of brushing, meanwhile, can be screamingly clear. On cat forums and Twitter, the cat-toothbrushing-phobic joke about losing their fingers. But what a lot of people are really afraid of sacrificing is their cat’s love. Broken trust can mar the relationship between owner and pet, Perrone said; people simply can’t communicate to skittish animals that this act of apparent torture is for their own good. Some cats never learn to deal. Even among veterinary experts, toothbrushing rituals are rare. Peralta and his wife just try to clear the bar of “at least once a week” with their own cat, Kit Kat; Berg and Perrone don’t brush their felines’ teeth at all. (Tsugawa does not currently own a cat, but he wasn’t a brusher when he did.)

I’m no pro, but I feel a bit torn too. I never took the time to teach Calvin and Hobbes to see toothbrushing as a treat, and they can get pretty grumpy during the ritual itself. Valeika, the North Carolina vet, told me that seeing Boocat’s horrified reactions was the main thing that prompted him to quit the brush. “She would hate it if we were always doing that to her,” he said. “She really would just not be our pet anymore.”

Feline-health experts know they’re losing this fight. “A lot of us are not even talking about toothbrushing anymore, because nobody’s doing it,” Berg said. Luckily, a few well-vetted alternatives to toothbrushing do exist. Berg and Delgado use specialty kibble that can cut down on plaque, and Perrone’s cat, Noriko, is into Greenies dental treats—both options that many pets may be more receptive to. Scientifically, nothing beats bona fide brushing. But realistically, this young art may already be obsolete. The best interventions, Delgado told me, will be the ones that people actually use. “If someone in my profession doesn’t brush their pet’s teeth,” Berg said, “I can’t blame anybody else.”