Rachel Gutman-Wei | The Atlantic

It Matters If It’s COVID

2024-09-04T17:26:00-04:00

You might have already guessed this from the coughs and sniffles around you, but a lot of people are sick right now, and a lot of them have COVID. According to the CDC’s latest data, levels of SARS-CoV-2 in wastewater are “very high” in every region of the country; national levels have been “very high” for about a month. Test positivity is higher now than it was during the most recent winter surge: Many people who seem like they might have COVID and who are curious or sick enough to get a test that’s recorded in these official statistics are turning out to, indeed, have COVID.

COVID-19 remains deadlier than the flu, and has the potential to cause debilitating symptoms that can last for years. It sends far more people to the hospital than RSV. But as of March, the CDC does not distinguish among these respiratory viruses—or any others—in its advice to the American public. If you’re sick, the agency advises, simply stay home until you’ve been fever-free and your symptoms have been improving for 24 hours. These days, hardly any public spaces specifically exclude people with an active COVID infection. Numerous sick people are not bothering to test themselves for the virus: Compared with 2022 and even 2023 numbers, sales of at-home COVID tests have tanked.

Why, at this point, should anyone bother to figure out what they’re sick with? One answer is treatment. Getting a prescription for the antiviral Paxlovid requires confirming a COVID infection within the first five days of sickness. But there’s an extra reason for every American to test this second if they’re feeling under the weather: Our current COVID wave is crashing right into vaccine season, and knowing when your most recent infection was is crucial for planning your autumn shot.

Immunology is a slippery science, so vaccine timing is not one size fits all. But as I reported in 2022, immunologists generally advise spacing out your doses from one another, and from bouts of COVID itself, by at least three months in order to maximize their effects. (The CDC advises waiting three months after COVID but four months after a shot if you’re eligible for more than one a year.) If your immune system is left in peace for long enough after a vaccine or infection, it can generate cells that provide durable protection against disease. Getting a COVID shot too soon after an infection might interrupt that process, compromising your long-term defenses. At the very least, in that scenario the vaccine “just probably won’t really do much,” says Jenna Guthmiller, an immunologist at the University of Colorado, because your immune system would already have been activated by the infection.

[Read: A simple rule for planning your fall booster shot]

This is why knowing whether you have COVID right now is worthwhile. Pharmacies around the country are currently giving out Moderna’s and Pfizer’s 2024 vaccines; last week, Novavax received FDA authorization for its updated formula, which should be available soon. But if you’ve just had COVID, now is exactly when you don’t want a shot. (There are some exceptions to the three-month rule: For people who are immunocompromised, older, or otherwise high-risk, the short-term protection against infection that vaccination offers can outweigh any drawbacks.) When you do want the shot is another question. Ideally, you would get the vaccine a couple of weeks before you’re most likely to be exposed, whether because you’re gathering in large groups for the holidays or because the virus is surging in your community. If, say, you come down with COVID today, you might want to wait until as close to Thanksgiving as possible before getting an updated shot.

If you do have COVID this month—or if you had it this summer—the genetic makeup of the virus that infected you is almost certainly not identical to what’s in the newest vaccines. Pfizer’s and Moderna’s shots were based on a variant called KP.2, which was dominant in May. The Novavax formula is built around JN.1, which ruled the COVID landscape way back in January. Newer variants are far more common now, including KP.3 and LB.1. But wait long enough past an August or September infection and a somewhat-outdated vaccine should still boost your immunity. “If the vaccine is X and you got infected with Y, the vaccine of X is going to boost immunity that cross-reacts with Y,” Guthmiller told me. “And that still puts you in a fine place to combat Y, and then Z”—whatever variant comes next.

Part of the reason that infection and vaccination timelines are colliding is because, despite attempts to respond to COVID with the American flu toolkit, SARS-CoV-2 is simply not following flu’s usual winter schedule. “Flu is, for the most part, very predictable,” Guthmiller said. COVID has an approximate seasonal pattern, but instead of a single winter wave, it’s so far landed on twice-yearly surges, the timing, size, and precise dynamics of which remain unpredictable. This year’s summer wave, for example, dwarfs last year’s, and started earlier. And yet the CDC recommends most Americans get a COVID vaccine once a year, beginning right around now, when many people have recently been infected. (People over 65, and those with certain immune conditions, are allowed multiple shots a year.)

[Read: Why are we still flu-ifying COVID?]

All of this is happening while Americans are getting progressively less information about how much COVID is spreading through their communities. The CDC stopped reporting new daily COVID infections in May 2023. This April, it stopped requiring hospitals to submit their COVID data to its national disease-monitoring network. (Last month, the agency announced that hospitals must report on COVID, RSV, and flu beginning on November 1.) Still, the information we do have suggests that any respiratory illness you might get right now has a decent chance of being caused by SARS-CoV-2. Testing remains the best way to know, with reasonable confidence, whether it is. But unless you have some tests stockpiled, you’ll have to buy them yourself. The program that sent a handful of free kits to each American household in 2022 and 2023 was paused in March, and the federal government won’t start taking orders for free COVID tests again until the end of the month.

How Risky Is COVID for an 81-Year-Old?

2024-07-17T21:54:00-04:00

Today, for the third time in two years, President Joe Biden tested positive for COVID-19, the White House said. The president was in Las Vegas—attempting to convince voters, donors, and his fellow lawmakers that he is still the candidate best poised to defeat former President Donald Trump in November—when he fell ill with a runny nose and cough, according to a White House statement. He’s already taking the antiviral Paxlovid and will isolate at his home in Delaware.

Since Biden’s first two COVID bouts—an initial case and a rebound shortly thereafter in 2022—much has changed for the president, and for the trajectory of the pandemic. Biden’s cognitive abilities have come under more intense scrutiny, especially following a debate with Trump last month in which the president demonstrated difficulty completing sentences and holding on to a train of thought. Reported rates of COVID infections, hospitalizations, and deaths have declined—thanks in large part to vaccination—and precautions have become ever more rare. Biden is vaccinated and has superb access to medical care. Chances are, he will be fine. Yet one basic fact remains unchanged: COVID is still capable of inflicting great damage, especially upon the elderly.

In June, according to provisional CDC data, about four out of every 100,000 Americans over the age of 75 (or 0.004 percent) died with COVID-19. That’s a far cry from the staggering fatality rates of 2020 (roughly 0.17 percent for the same age group in April of that year), but still sizable in comparison with younger Americans’ risk. The June 2024 COVID death rate among 30-to-39-year-olds, for example, is two out of every 10 million. Hospitalizations tell a similar story for the elderly: Last month, more than 60 out of every 100,000 Americans over 75 were hospitalized with COVID. And according to the CDC, this is likely an undercount.

Still, the risks of COVID seem to increase over even just a few years of life for the elderly. People 75 or older are currently 3.5 times as likely to be hospitalized and seven times as likely to die with COVID as people ages 65 to 74. And people in their 80s can accumulate health problems with startling speed. Heart disease, diabetes, kidney disease, cancer, and stroke—all maladies more likely to affect older people—increase a person’s chances of serious complications from COVID.

Biden is as likely as any American of his age to come away from this infection with minimal long-term effects. So far, according to the White House’s statement, his symptoms are mild, he has no fever, and his blood-oxygen level is normal. He was first vaccinated against COVID in 2020 and has received several shots since, most recently in September. Vaccines are proven to mitigate the most serious risks of the disease, especially among the elderly. And should things take a turn, Biden, as president, has care teams and resources at his instant disposal.

That said, as far as COVID is concerned, good for an 81-year-old is not reliably good. And COVID does not have to kill someone to have troubling, lasting effects. Even mild bouts of COVID can lead to symptoms that linger for weeks or years and range from inconvenient to debilitating. In a study published today, about 7.8 percent of patients infected since Omicron became the dominant variant in the United States developed long-term symptoms. Given current concerns about the president’s health and brainpower, any further deterioration is a sobering prospect. A report published by the National Academies of Science last month found that older Americans are especially at risk of cognitive impairment following a COVID infection. What would that mean for a man who has already shown signs of substantial decline—a man subjected to the rigors of one of the most demanding jobs on the planet during the most crucial political campaign of our lifetimes, who refuses to lift the burden of American democracy from his aging shoulders?

Ten days ago—after Biden’s feeble debate performance, but before a gunman attempted to assassinate his opponent at a rally—the president made a perplexing statement. Addressing the crowd at a Pennsylvania campaign event, he declared, “I ended the pandemic.” The reality is that COVID continues to upend lives every day. Americans should be mindful that it could still upend elections, too.

Lila Shroff contributed reporting.

Baltimore Lost More Than a Bridge

2024-03-26T13:01:52-04:00

You could see the Francis Scott Key Bridge from Fort McHenry, the pentagon-shaped keep that inspired the bridge’s namesake to write the verses that became our national anthem. You could see it from the pagoda in Patterson Park, another strangely geometric landmark from which I’ve cheered on teams at Baltimore’s annual kinetic-sculpture race. You could see it from the top of Johns Hopkins Hospital, the city’s biggest employer. This morning, my husband sent me a photo of the familiar view out his window at work—now dominated not by the soaring bridge, but by a hulking container ship, halted in the middle of the water with metal strewn over and around it.

Videos of the bridge’s collapse are stunning. At about 1:30 a.m., the ship, called the Dali, lost power and crashed into one of the bridge’s central pillars. Within 15 seconds, the straight line of the bridge’s span bends and breaks, and the entire structure tumbles into the harbor.

The bridge was one of only three roadways crossing Baltimore’s defining waterways, and until this morning, each of those routes served its own purpose. The I-95 tunnel, which cuts across the mouth of the harbor, was for people commuting between Baltimore and Washington, D.C. The famously congested Baltimore Harbor Tunnel—part of I-895—passes beneath the Patapsco River and was for people bypassing the city completely. The Key Bridge, farther down the river toward the Chesapeake Bay, handled the least traffic of the three. But it was part of the Baltimore Beltway, the circular highway that forms the unofficial boundary of the Baltimore metro area and shuttles suburbanites into the city to help make it run. Of the three routes, the Key Bridge was the most visible and beautiful, standing alone above the water in a long, graceful arch.

[David A. Graham: Why ships keep crashing]

Officials had enough notice of the Dali’s distress that it blocked cars from entering the bridge before its collapse, but Maryland’s transportation secretary told reporters this morning that the department was searching for six missing construction workers who may have fallen into the 48-degree water. The crew was working to fix potholes—to keep Baltimore’s beat-up roads in good enough shape to keep traffic flowing into the city. Two workers have already been pulled from the water, one of whom was in such bad shape that they couldn’t be asked what happened. As of about 10:08 a.m., no one but the construction crew was believed to have fallen into the water. But had the collapse happened a few hours later, hundreds of people might well be dead: On average, about 31,000 cars and trucks cross the bridge every day.

The cars, for now, can be rerouted. But the remnants of the bridge (not to mention the Dali) are blocking the city’s waterways for any other ships that are scheduled to enter. Baltimore is now America’s 17th-biggest port by tonnage—a respectable rank, if a far cry from the early days of the United States, when shipping made the city the third-most-populous in the country—and may well drop further down the list if the harbor remains inaccessible. (Maryland Governor Wes Moore has yet to comment on when the port might reopen for business.) But Baltimore is a city defined by water. The Gwynns Falls and the Jones Falls trickle through our parks. The Inner Harbor is our Times Square; our economy is tied up in trade and transportation. Ships are in the city’s bones. The brackish harbor is in its heart.

Baltimore is also a city that can’t catch a break, full of people who find joy in its absurdities. The Trash Wheel Family—a set of four solar and hydro-powered, googly-eyed machines that keep litter in the city’s rivers from entering the harbor—are local celebrities. Every week, a group of magnet-fishers meets at the harbor to pluck benches, scooters, and other treasures from the water, proudly displaying their haul along the sidewalk. Every year, bicycle-powered moving sculptures shaped like dragons and dogs and fire trucks compete to paddle down a short stretch of the harbor without capsizing. But no one ever really forgets that the harbor itself is visibly polluted, that much of the city’s infrastructure is breaking and broken, that the state has held back funding to fix it, that Baltimore’s mayoral administrations have been riddled with corruption, that people are still getting by on too little, that the murder rate is still too high.

[Read: The aftermath of the Baltimore bridge collapse]

Baltimore Harbor is one of the city’s most important links to the rest of the world; to cut it off is to clog our blood supply. Moore has already said that the bridge will be rebuilt to honor this morning’s victims. We can still get out of the city with trains and cars. But this morning, Baltimore feels that much more claustrophobic. Looking out toward the Chesapeake used to be an exercise in optimism, in feeling all the possibilities of being connected to the wider world and the terrifyingly wide swell of the Atlantic. Today, it’s an exercise in mourning and resolve.

The Art of Communing With Trees

2024-03-21T10:23:00-04:00

This is an edition of Time-Travel Thursdays, a journey through The Atlantic’s archives to contextualize the present and surface delightful treasures. Sign up here.

Trees can seem like timeless beings. Many a giant sequoia has racked up three millennia on this Earth. A pine in California’s White Mountains is estimated to be nearly 5,000 years old. A colony of aspens in Utah may well have originated during the Stone Age, and to this day, its leaves glitter gold in the autumn sun.

A tree’s life span, undisturbed by axe or fire, is utterly divorced from the scales on which human affairs operate. And yet, throughout history, people have seen themselves reflected in trees. One of those people was James Russell Lowell, a poet who served as The Atlantic’s first-ever editor. “I care not how men trace their ancestry / To ape or Adam; let them please their whim; / But I in June am midway to believe / A tree among my far progenitors,” Lowell wrote in The Atlantic’s June 1868 issue. He even suggests that “many a lifelong leafy friend” returns his affection: “Surely there are times / When they consent to own me of their kin.”

Lowell’s poem goes on to compare trees to ancient nymphs and to the very spirit of hospitality. But none of these images is as convincing as his vision of ancestor-trees, watching over children’s games and singing “faint lullabies of eldest time.” In June, how can one understand a tree as anything but eternal? It seems no more movable than the earth in which it is planted, incapable of anything but endless growth. Trees may be inscrutable—we can’t discern much about their inner lives—but when they are lush with leaves, they are undeniably certain.

Unlike Lowell, I feel most kinship with trees not when the first hot breaths of summer bathe the Northern Hemisphere, but at this time of year, when any given day might yield snow or blinding sun, or both. In spring, when the first hopeful blossoms and buds begin to pepper bare branches, a tree’s life suddenly moves as quickly as mine, if not quicker. The blooms’ frailty and evanescence seem transposed onto the entire organism, and suddenly, the tree is not an ancestor-deity, but mortal.

Even an ancient tree can seem childlike in March. In a story published in The Atlantic in 1877, a man walking through a grove remarks, “Trees, like children, reveal peculiarities of character more frankly in their budding-time than at maturer stages.” When trees fail to obscure their limbs, the narrator observes, ashes look especially feminine, and young oaks particularly athletic. Like children, they are vulnerable too: The man so fond of budding trees laments to an oak that men are “apt to fall treacherously upon you with the axe,” a tendency he deems a “special American barbarism.”

Ancestor-trees, child-trees: What are we to make of a life that can age and grow young again at the turn of the seasons, that equally distends and contracts our perception of time? Perhaps it is just this ambiguity that allows trees to be such a powerful avatar of humanity. Life, after all, is full of distended and contracted seasons.

In recent years, unpredictable weather has added new confusion to our already fluid sense of time’s passage. The country just experienced its warmest winter on record. In Maryland, where I live, half a foot of snow fell in mid-January; a week later, the weather was practically beachy. When I traveled to Vermont last month, the temperature rose 53 degrees in two days. The famous cherry blossoms in Washington, D.C., reached peak bloom last Sunday, earlier than almost any year on record.

I visited D.C’s Tidal Basin the day before peak bloom to commune with the child-trees, and found that the unnamed narrator in that 1877 story had a point: Each tree’s character was on full display. There were slender trees and muscular trees, trees that curved and trees whose limbs angled sharply, trees that reached high and trees whose lowest branches needed to be jumped over, trees that twisted and trees that stretched from the ground like telephone poles. The flowers were saturated pink and cottony white, scent-free and fragrant. Some trees were flush with blossoms, while others had only begun to bud.

Spectacular and ancient and delicate as the trees were, I didn’t immediately see them as ancestors or children or nymphs. Perhaps that shouldn’t have been a surprise. As the narrator said of his own dear trees, “All who knew the oaks seemed to have a conviction that they alone could understand them.” But as I shuffled along with the crush of people in the Tidal Basin, I found that the cherry blossoms had at least one ancestral effect: They had brought us all together to pay our respects to a shared inheritance.

The Least Common, Least Loved Names in America

2024-01-02T08:00:00-05:00

When my husband and I got married, we decided we should share a last name, and that the name should be hyphenated. He didn’t want to lose a marker of his Chinese heritage, and I didn’t want to co-opt one—or give up my name if he wasn’t giving up his. So we just smushed our names together on the marriage license, figuring this was a normal thing to do, or at least unobjectionable.

But objections have indeed been raised. Not yet to my face—the worst I’ve heard has been along the lines of “I’d never hyphenate, but that’s great for you.” But I also know that anti-hyphen sentiment is widely shared: Very few American newlyweds hyphenate their names, survey data show, and it’s not hard to find op-eds that describe the practice as “crazy” and “pretentious”—the sort of arrangement that might produce a maladjusted, antisocial human being along the lines of, say, Sam Bankman-Fried.

My husband and I were both bemused to discover that names like ours could inspire so much antipathy. Why does a silly little hyphen make so many people uncomfortable, or unsettled, or even—God forbid—uncomfortable-unsettled?

If Americans are overly concerned with one another’s surnames, most of that concern is directed at women. The most basic New York Times wedding announcements for opposite-sex couples describe what the bride will do with her name as the second detail offered about her—after her age, before her job. (“The bride, 23, will take her husband’s name.”) What the groom does with his name is not mentioned.

Sociologists find that women also bear the brunt of judgment for making nontraditional surname choices. For a study that came out last year, Kristin Kelley, a sociologist now at the American Institutes for Research, asked about 500 people of various ages and education levels to assess a fictional engaged couple, “David Miller and Amanda Taylor,” who planned to use one of several surname arrangements: They would either keep their own names, call themselves the Millers, or change both their names to Miller-Taylor. Kelley found that “Amanda Miller-Taylor” was perceived as being a less committed and ideal spouse than “Amanda Miller,” and that “David Miller-Taylor” was seen as less ideal than “David Miller.” (The penalty for hyphenation was only half as big for David as it was for Amanda.)

[Read: Men should consider changing their last names when they get married]

An earlier survey of such attitudes, from 2002, found the opposite tendency among a set of about 200 mostly white freshmen at a small, private university in Illinois. When asked to compare married people with hyphenated names to “average” married people, the students generally had very favorable impressions, describing the female partners as more outgoing and sociable, and the male partners as especially committed and nurturing.

These different survey results could be a function of education and class, with those from more privileged backgrounds more willing to accept an unconventional naming choice. But the older study was also conducted at a time when hyphenated names may have seemed more normal. College freshmen of that era would have been children of the 1980s, and grown up among the naming trends associated with second-wave feminism. According to the 2002 paper, 11 percent of the college’s female faculty used a hyphenated name. Compare that with a Pew survey conducted last April, which found that only 5 percent of women with postgraduate degrees who married men chose to hyphenate their names.

The exact prevalence of hyphenate naming in the ’80s, and its trajectory since then, are frustratingly unclear. The nice people at the U.S. Census Bureau couldn’t help me track hyphens over time; neither could the nice people at the wedding company The Knot. We do know that hyphenation rates have been flat at roughly 5 percent among professional women’s basketball players since the 1990s, and that the rate among congresswomen was 3 percent in 2015 and is around 4 percent today.

Among men, the practice is even less common. The Pew survey found that fewer than 1 percent of men who marry women choose to hyphenate their names, while 5 percent take their wife’s name outright. Perhaps some men choose the latter because it’s more discreet. “If your name is hyphenated, it’s maybe pretty obvious that you changed it when you got married,” Emily Shafer, a sociologist at Portland State University, told me. But if you take your wife’s name, people may simply assume that she took yours.

These tendencies are even built into the legal system: When Hannah Haksgaard, a law professor at the University of South Dakota, cataloged the state-level statutes concerning marital name change in 2019, she found that many states still technically disallow men from swapping their surnames at marriage. Those rules are unenforceable, she told me, because they violate the Fourteenth Amendment’s equal-protection clause. But they reflect a surprisingly popular, surprisingly extreme attitude toward marital naming: In one survey from 2006, half of respondents agreed that past laws requiring women to adopt their husband’s name had been a good idea.

[Read: A patriarchal tradition that just won’t budge]

I’ve never heard this thought expressed out loud, though one of my college friends did once insist that he’d never marry a woman who wouldn’t take his name. In fact, my hyphenation gets less attention than my husband’s: Every so often he will reveal to a friend or colleague that he’s hyphenated, and I can all but hear the record scratch. “Oh, really?” they might say, sometimes followed by a “Huh, that’s cool”—or, better yet, “I’ve never heard of anyone doing that.” I don’t think they’re passing moral judgment, but they do seem a bit uncomfortable-unsettled.

Some may worry that a name like ours is a burden. “Hyphenating names is basically a pain in the ass in all the practical ways that you can think of,” Laurel Sutton, a professional namer and the president of the American Name Society, told me. It can lead to mismatches between plane tickets, passports, and driver’s licenses, for example. (I’ve found that flying comes up a lot in anti-hyphenation arguments.) Sutton also cited some people’s concern for future generations: What if your hyphenated child gets married? Does a double name turn into a triple, or even a quadruple?

I’ve also heard the claim from friends and colleagues (and, of course, on the internet) that hyphenated names in general—or combinations of two particular names—are unpleasant and unwieldy, just too ugly. But such aesthetic preferences are largely a product of our cultural conditioning, Kelley told me, and may serve as a cover for unease with challenging a well-established practice. “A lot of people just are grossed out by the idea of having a hyphenated surname,” she said. They may find it easier to say That’s an ugly name than to cop to their unwillingness to violate a social norm. And as a recent hyphenator, I can say with some authority that Gutman-Wei rolls off the tongue just fine. It’s also not in fact a bureaucratic nightmare (at least not yet). I’ve flown with this name several times, including internationally, and never had a problem.

As for the future-generations problem, it’s true that my potential kids could end up having to make a fresh decision about their married names. (Neither my husband nor I will be offended however they decide to proceed; in his words, “They can do whatever they want.”) But really, everyone who gets married makes that choice. As a culture, we simply overlook many of those choices, most notably when they’re made by the 92 percent of men who keep their name.

Americans Don’t Get to Have the Best New COVID Drug

2023-10-25T14:25:42-04:00

Japan is home to an untold number of conveniences and delights that American consumers regularly go without: Faster public transit! Better sunscreen! Lychee KitKats! But as we head into sick season, one Japanese invention would be especially welcome on the U.S. market: an antiviral pill that appears to shorten COVID symptoms, might protect against chronic disease, and doesn’t taste like soapy grapefruit.

Ensitrelvir, a drug made by the Osaka-based pharmaceutical company Shionogi, was conditionally approved in Japan last November. Like Paxlovid, ensitrelvir works by blocking an enzyme that the SARS-CoV-2 virus uses to clone itself inside the human body. But for the millions of Americans who will likely get COVID in the coming months, the new drug is almost certain to be out of reach. In 2021, Pfizer waited just five weeks for Paxlovid to receive its emergency use authorization. But ensitrelvir is still sitting in the approval pipeline, stuck in another round of clinical trials that may run well into 2024.

Existing data (not all of which have been peer-reviewed) show that people with COVID who promptly take ensitrelvir, marketed as Xocova in Japan, test negative about 36 hours faster than people who take a placebo. Fever, congestion, sore throat, cough, and fatigue disappear about a day earlier too. Even smell and taste loss appear to resolve more quickly. The company also has some tentative evidence suggesting that the drug can help protect patients from developing long COVID.

These findings were not enough for the FDA, but they are extremely encouraging, says Michael Lin, a bioengineering professor at Stanford University who works on drugs for treating coronavirus infections. Xocova “looked as good or a little bit better than Paxlovid,” he says. For instance, Pfizer’s clinical trials failed to show that Paxlovid clears symptoms any faster than a placebo in people who aren’t at high risk of developing severe COVID. Shionogi’s did just that.

Reshma Ramachandran, a family physician at Yale, told me that if the early Xocova results hold up in additional trials, she’d be inclined to prescribe it to her vaccinated patients in place of Paxlovid, simply because the evidence supporting its use is more direct. She said she’d be especially keen to give Xocova if the long-COVID finding can be reproduced.

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

No lab or pharmaceutical company has yet published a study that pits Xocova against Paxlovid head-to-head in treating COVID, so it’s impossible to say with certainty which one is better. You can’t draw conclusions just by comparing Pfizer’s clinical-trial results with Shionogi’s: Their drugs were tested in different populations with different levels of immunity at different points in the pandemic when different variants were circulating. Shionogi also required clinical-trial participants to start taking Xocova within three days of feeling sick, whereas patients in the Paxlovid trials began their treatment up to five days after symptoms started. Daniel Griffin, an infectious-disease specialist at Columbia University, told me that timing is everything when it comes to antivirals: In general, the sooner a patient starts taking a drug, the better it works.

A Pfizer spokesperson told me that the efficacy and adverse-event rates of Paxlovid and Xocova cannot directly be compared, and emphasized Paxlovid’s power to stave off hospitalization and death. (Xocova’s clinical trials were not able to provide meaningful data on those outcomes, which are now much rarer than they were in 2021.) “Since the beginning of the pandemic, we’ve known it will take multiple treatment options and preventative measures for the world to overcome the challenges of COVID-19,” he said in an email.

Even if Xocova turns out to be no more effective than Paxlovid, it still has several practical advantages. For one thing, it is literally easier to swallow. Paxlovid must be taken twice a day for five days, and each time you have to gulp down three pills: two containing nirmatrelvir (which actively combats the virus), plus one containing ritonavir (which slows the metabolization of nirmatrelvir, keeping it in your system longer). Xocova is taken just once a day for five days, and after the first three-pill dose, it’s one pill at a time. Paxlovid can also cause dysgeusia, a.k.a. Paxlovid mouth—a sour, metallic, taste that may last for hours after swallowing. Xocova seems to taste just fine.

[Read: Paxlovid mouth is real—and gross]

Experts hope that Xocova will be more widely accessible than Paxlovid, too. Pfizer announced last week that the price of Paxlovid will soon rise from $529 to $1,390 when the drug enters the commercial market. Shionogi hasn’t decided on Xocova’s price in the U.S. market, but there’s reason to think it will be cheaper. In Japan, the only market where both drugs are currently available, a course of Xocova costs 51,851 yen (about $346), and Paxlovid is nearly double the price, at 99,027 yen (about $661). And whereas Japanese health authorities—like those in the U.S.—have recommended Paxlovid for use by patients at high risk of severe COVID, Xocova has been shown to benefit people with infections regardless of their risk status. Finally, whereas Paxlovid’s reach is limited by its many harmful interactions with other drugs, Xocova might pose fewer problems because it doesn’t contain ritonavir, Lin told me. The newer drug’s interaction profile is still being ironed out, but a company spokesperson pointed me to a running list from the University of Liverpool. (According to that source, you should avoid taking Paxlovid and Adderall at the same time—but going on Xocova is fine.)

Xocova may also sidestep one of patients’ most commonly voiced concerns about Paxlovid: that it will make their COVID go away and then return. One recent observational study of COVID patients found that symptoms rebounded among 19 percent of Paxlovid takers, versus 7 percent of nontakers. By contrast, Shionogi has reported that symptom rebound was vanishingly rare in its clinical trials of Xocova.

[Read: Inside the mind of an anti-Paxxer]

Neither Shionogi nor the FDA would give me an estimate of Xocova’s approval timeline in the U.S., but earlier this year, the company’s CEO estimated that it might get the nod in late 2024. This past spring, the FDA gave the drug “fast track” status, which means Xocova will be eligible for an expedited review process once the company submits its application. (The FDA declined to comment on Xocova’s prospects for approval, citing federal disclosure laws.) Until then, it’s running more clinical trials in the U.S. and abroad. One of them, conducted in partnership with the National Institutes of Health, will evaluate the drug’s performance in hospitalized patients. Another will evaluate its efficacy against long COVID, among other things.

To some experts, Xocova’s track is not nearly fast enough. David Boulware, an infectious-disease specialist at the University of Minnesota, told me that the FDA appears to be “slow walking” the approval process. Lin, too, would like to see more action. But it’s not clear how, exactly, that would happen. “I think the FDA is doing all that they can,” Ramachandran said; an emergency use authorization for Xocova isn’t a realistic option, given that the COVID public-health emergency has expired. Plus, Griffin said, caution is prudent when dealing with new drugs. “We want to make sure it’s safe. We want to make sure it’s effective,” he told me. “We also don’t want to fall into the trap we fell in with molnupiravir,” an earlier antiviral that looked promising at first, but ultimately offered disappointing benefits to COVID patients (though a surprising utility for cats).

If the FDA were to approve Xocova tomorrow, demand for Paxlovid likely wouldn’t disappear, experts told me. Lin said the two drugs might compete for users, like Motrin and Aleve. People who are in danger of being hospitalized or dying from COVID could still opt for Paxlovid. “But there’s a much larger group of people who just feel crummy, and they just want to feel better,” Griffin told me. For them, Xocova could make more sense. They just won’t have a choice until the FDA approves it.

We Have No Drugs to Treat the Deadliest Eating Disorder

2023-09-07T10:32:32-04:00

Updated at 12:21 p.m. on September 8, 2023

In the 1970s, they tried lithium. Then it was zinc and THC. Anti-anxiety drugs had their turn. So did Prozac and SSRIs and atypical antidepressants. Nothing worked. Patients with anorexia were still unable to bring themselves to eat, still stuck in rigid thought patterns, still chillingly underweight.

A few years ago, a group led by Evelyn Attia, the director of the Center for Eating Disorders at New York Presbyterian Hospital and the New York State Psychiatric Institute, tried giving patients an antipsychotic drug called olanzapine, normally used to treat schizophrenia and bipolar disorder, and known to cause weight gain as a side effect. Those patients in her study who were on olanzapine increased their BMI a bit more than others who were taking a placebo, but the two groups showed no difference in their cognitive and psychological symptoms. This was the only medication trial for treating anorexia that has shown any positive effect at all, Attia told me, and even then, the effects were “very modest.”

Despite nearly half a century of attempts, no pill or shot has been identified to effectively treat anorexia nervosa. Anorexia is well known to be the deadliest eating disorder; the only psychiatric diagnosis with a higher death rate is opioid-use disorder. A 2020 review found people who have been hospitalized for the disease are more than five times likelier to die than their peers without it. The National Institutes of Health has devoted more than $100 million over the past decade to studying anorexia, yet researchers have not found a single compound that reliably helps people with the disorder.

Other eating disorders aren’t nearly so resistant to treatment. The FDA has approved fluoxetine (a.k.a. Prozac) to treat bulimia nervosa and binge-eating disorder (BED); doctors prescribe additional SSRIs off-label to treat both conditions, with a fair rate of success. An ADHD drug, Vyvanse, was approved for BED within two years of the disorder’s official recognition. But when it comes to anorexia, “we’ve tried, I don’t know, eight or 10 fundamentally different kinds of approaches without much in the way of success,” says Scott Crow, an adjunct psychology professor at the University of Minnesota and the vice president of psychiatry for Accanto Health.

The discrepancy is puzzling to anorexia specialists and researchers. “We don’t fully understand why medications work so differently in this group, and boy, do they ever work differently,” Attia told me. Still, experts have some ideas. Over the past few decades, they have been learning about the changes in brain activity that accompany anorexia. For example, Walter Kaye, the founder and executive director of the Eating Disorders Program at UC San Diego, told me that the neurotransmitters serotonin and dopamine, both of which are involved in the brain’s reward system, seem to act differently in anorexia patients.

Perhaps some underlying differences in brain chemistry and function play a role in anorexia patients’ extreme aversion to eating. Or perhaps, the experts I spoke with suggested, these brain changes are at least in part a result of patients’ malnourishment. People with anorexia suffer from many effects of malnutrition: Their bones are more brittle; their brain is smaller; their heart beats slower; their breath comes shorter; their wounds fail to heal. Maybe their neurons respond differently to psychoactive drugs too.

[Read: The challenge of treating anorexia in adults]

Psychiatrists have found that many patients with anorexia don’t improve with treatment even when medicines are prescribed for conditions other than their eating disorder. If an anorexia patient also has anxiety, for example, taking an anti-anxiety drug would likely fail to relieve either set of symptoms, Attia told me. “Time and again, investigators have found very little or no difference between active medication and placebo in randomized controlled trials,” she said. The fact that fluoxetine seems to help anorexia patients avoid relapse—but only when it’s given after they’ve regained a healthy weight—also supports the notion that malnourished brains don’t respond so well to psychoactive medication. (In that case, the effect might be especially acute for people with anorexia nervosa, because they tend to have lower BMIs than people with other eating disorders.)

Why exactly this would be true remains a mystery. Attia noted that proteins and certain fats have been shown to be crucial for brain function; get too little of either, and the brain might not respond to drugs in expected ways. Both she and Kaye suggested a possible role for tryptophan, an amino acid that humans get only from food. Tryptophan is converted into serotonin (among other things) when we release insulin after a meal, Kaye said, but in anorexia patients, whose insulin levels tend to be low, that process could end up off-kilter. “We suspect that that might be the reason why [SSRIs] don’t work very well,” he said, though he emphasized that the theory is very speculative.

In the absence of meaningful pharmacologic intervention, doctors who treat anorexia rely on methods such as nutrition counseling and psychotherapy. But even non-pharmaceutical interventions, such as cognitive behavioral therapy, are more effective at treating bulimia and binge-eating disorder than anorexia. Studies from around the world have shown that as many as half of people with anorexia relapse.

Colleen Clarkin Schreyer, a clinical psychologist at Johns Hopkins University, sees both patients with anorexia nervosa and those with bulimia nervosa, and told me that the former can be more difficult to treat—“but not just because of the fact that we don’t have any medication to help us along. I often find that patients with anorexia nervosa are more ambivalent about making behavior change.” Bulimia patients, she said, tend to feel shame about their condition, because binge eating is stigmatized and, well, no one likes vomit. But anorexia patients might be praised for skipping meals or rapidly losing weight, despite the fact that their behaviors can be just as dangerous over the long term as bingeing and vomiting.

[Read: Raising a daughter with a body like mine]

Researchers are still trying to find substances that can help anorexia patients. Crow told me that case studies testing a synthetic version of leptin, a naturally occurring human hormone, have produced interesting data. Meanwhile, some early research into using psychedelics, including ketamine, psilocybin, and ayahuasca, suggests that they may relieve some symptoms in some cases. But until randomized, controlled trials are conducted, we won’t know whether or how well any psychedelic really works. Kaye is currently recruiting participants for such a study of psilocybin, which is planned to have multiple sites in the U.S. and Europe.

Pharmaceutical companies just don’t seem that enthusiastic about testing treatments for anorexia, Crow said. “I think that drug makers have taken to heart the message that the mortality is high” among anorexia patients, he told me, and thus avoid the risk of having deaths occur during their clinical trials. And drug development isn’t the only area where the study of anorexia has fallen short. Research on eating disorders tends to be underfunded on the whole, Crow said. That stems, in part, from “a widely prevailing belief that this is something that people could or should just stop … I wish that were how it works, frankly. But it’s not.”

This article previously suggested that drugs are metabolized in the brain. In fact, they are metabolized mostly in the liver.

Birth Control Isn’t the Only Thing That Just Went Over-the-Counter

2023-07-14T14:54:32-04:00

The FDA announced yesterday that it had for the first time approved a daily birth-control pill for over-the-counter sales. That’s a big change; once the product, called Opill, is on the market—which may be as soon as early 2024—Americans will be able to buy daily hormonal birth control without a prescription. That’s historic news, but hidden underneath it is another set of firsts: In the coming months, Americans will also be able to grab an over-the-counter treatment for their heavy periods, cramps, headaches, and even migraines; they’ll have prescription-free access to a drug for endometriosis and polycystic ovary syndrome; and they’ll be able to buy a medication that can mitigate the symptoms of menopause. It’s all in the same, progestin-based pill.

The FDA’s approval only covers Opill’s use as a form of birth control, but doctors have been prescribing pills that contain progestin for noncontraceptive needs for years. For the most part, the intervention works much better when the pills include both progestin and estrogen. Adding that second hormone to the mix amplifies all of progestin’s beneficial effects, plus helps control hormonal acne. It also leaves more wiggle room in terms of timing: Progestin-only pills—sometimes called a minipill—have a much shorter half-life in the body, so if you don’t take them during the same three-hour window each day, they’re much less reliable at preventing pregnancy, says Anne-Marie Amies Oelschlager, the chief of pediatric and adolescent gynecology at Seattle Children’s. (Some women are prescribed progestin-only pills because they are particularly susceptible to certain risks associated with estrogen.)

As a result, an over-the-counter progestin-only pill is far from the best way of treating these conditions, experts told me. “While I suppose that it could be used off-label, I would be hesitant to do that if someone was otherwise able to obtain a prescription for a combined oral contraceptive,” Erin Fleurant, a family-planning fellow at Northwestern Medicine, told me. And if progestin by itself really were the right approach, then an IUD, implant, or injection might be a more effective way to deliver the drug.

[From July 1939: The responsibilities of birth control]

Despite the fact that progestin on its own would not usually be a doctor’s first choice—“I generally don't prescribe it,” Veronica Ades, the vice chair of ob/gyn at Jacobi Medical Center, told me—the drug can have meaningful benefits when taken on its own. Amies Oelschlager told me that she prescribes it to suppress patients’ periods, especially if they’re experiencing pain or heavy bleeding. Even low-dose pills (like Opill) can be helpful for controlling period- and perimenopause-related migraines, as well as mood swings from premenstrual syndrome or premenstrual dysphoric disorder.

Progestin pills can also be used to treat endometrial hyperplasia, an abnormal thickening of the uterine lining (a.k.a. the endometrium) that can develop into cancer. Same for endometriosis, a condition that may affect up to 11 percent of American women in which endometrial tissue grows outside the uterus. Patients with PCOS produce unusually high levels of male sex hormones and, Ades said, generally have too much estrogen in their body relative to progesterone (the naturally occurring analogue of progestin). Progestin pills can help strike a healthier balance.

Right now, patients have few options to get relief from any of those symptoms without a doctor’s help. Until Opill hits the market, the best non-prescription way to treat PCOS is with healthy eating and exercise, Amies Oelschlager told me. For heavy periods, the best option patients can buy without a prescription is an NSAID like ibuprofen. “As far as an over-the-counter, daily hormonal medication, this is the first in the United States,” she said.

Perhaps the best circumstances for off-label use of Opill will be as a stopgap. If someone starts having abnormal bleeding or period pain but can’t get an appointment or travel to a doctor for several weeks, they could buy themselves some progestin-only pills for the interim. Opill could also be a backup plan for patients who are already taking birth-control pills for a non-birth-control purpose but can’t make it to their doctor to renew their prescription, or can’t get their prescription filled at a pharmacy.

[Read: A vaccine for birth control?]

Still, Ades cautioned that even stopgap use might not be wise for endometriosis patients, for whom switching medications could disrupt a delicate balance of hormones and “create a cascade of problems.” Fleurant warned that some of the symptoms that progestin pills could help alleviate may also be associated with very serious conditions that need a different treatment plan. “Say someone was 45 years old and having irregular bleeding and also had a lot of other risk factors for uterine cancer. I wouldn’t want them to pick up this pill and think that that was going to cure everything,” she said. Instead, they should be seen by a health-care provider.

For most women who need to be on birth control, a single-hormone drug like Opill is not the most reliable option; but starting next year, it could well be the most convenient. That same trade-off, between effectiveness and access, affects other uses of progestin, too.

How Handwriting Lost Its Personality

2023-07-11T13:01:23-04:00

Because I am a writer, and because I am a hoarder, my apartment is littered with notebooks that contain a mixture of journal entries and school assignments. Many pages don’t have dates, but I can tell which era of my life they correspond to just by looking at the handwriting. In the earliest examples, from elementary school, my print is angular, jagged; even the s’s and j’s turn sharp corners. In middle school, when I wanted to be more feminine (and was otherwise failing), I made my letters rounder, every curve a bubble ready to pop. In my junior year of high school, when it was time to get serious about applying to college, I switched to cursive, slender and tightly controlled.

Each of my metamorphoses was made in keeping with a centuries-old American belief that people—types of people, even—can be defined by how they write their letters. Now, though, this form of signaling may be obsolete. In the age of text on screens, many of us hardly write by hand at all, so we rarely get the chance to assess one another’s character through penmanship. Handwriting, as a language of its own, is dying out.

Over the centuries, the way people read that language has shifted. Until the 1800s, at least in the U.S., writing styles were less an act of self-expression than a marker of your social category, including your profession. “There were certain font types for merchants, for example, that were supposed to reflect the efficiency and the speed with which merchants work,” Tamara Plakins Thornton, a historian at the University at Buffalo and the author of Handwriting in America, told me. Lawyers used a different script, aristocrats another, and so on. The distinctions were enforced—by social norms, by teachers, by clients and colleagues and employers.

Men and women, too, were assigned their own fonts. Men were taught “muscular handwriting,” Carla Peterson, an emeritus professor of English at the University of Maryland, told me. They used roundhand, a larger script that was meant to be produced with more pressure on the quill or pen; women, by contrast, learned the narrower Italian script, akin to today’s italics. The latter style was compressed, says Ewan Clayton, a handwriting expert at the University of Sunderland, in the United Kingdom, in the same way that women’s waists might be limited by contemporary fashion. Eventually, women switched to using roundhand too.

[From the February 1859 issue: Ought women to learn the alphabet?]

The idea that handwriting styles might differ meaningfully from one person to another—and that those differences could be a means of showing your true nature—really took off in the 19th century, around the time that business correspondence and records started being outsourced to the typewriter. As penmanship was freed from professional constraints, it became more personal. “It was really believed that handwriting could be the articulation of self, that indeed the character of script said something about the character of a person,” says Mark Alan Mattes, an assistant English professor at the University of Louisville and the editor of the upcoming collection Handwriting in Early America.

Nowhere was that belief better exemplified than in the field of graphology—basically, phrenology for handwriting. In the 1840s, Edgar Allan Poe (who was taken with all manner of scientific measurements) published his analyses of the signatures of more than 100 writers, and how their lines and squiggles corresponded to each writer’s prose style. Of Henry Wadsworth Longfellow’s autograph, he wrote, “We see here plain indications of the force, vigour, and glowing richness of his literary style; the deliberate and steady finish of his compositions.” Poe was not as kind to the poet Lydia Sigourney: “From [the signature] of Mrs. S. we might easily form a true estimate of her compositions. Freedom, dignity, precision, and grace, without originality, may be properly attributed to her. She has fine taste, without genius.” An 1892 guide to graphology is more systematic, informing readers that people who connect all their letters at the base are “purely deductive” in their reasoning, while those whose letters have some elbow room are “purely intuitive.”

Samples of “purely intuitive” (top) and “purely deductive” (bottom) handwriting styles from Talks on Graphology by Helen Lamson Robinson and M. L. Robinson

Graphological tendencies continued into the early 20th century, when researchers published studies proclaiming that readers could guess a person’s gender from their script with better-than-chance accuracy—as if students hadn’t still been taught that boys and girls should write in different ways as of just a few decades prior. Through the 1970s, scientists were plumbing handwriting for character traits; one study found that “missing i dots are related to the nonsubmissive, non-egocentric, socially interested person,” whereas the “number of circled i dots relates positively to the intelligent and sophisticated personality.”

Handwriting analysis moved further toward the fringe in the age of computer connectivity, when typing took over. “We are witnessing the death of handwriting,” Time proclaimed in 2009. Things have only gotten more digital since then. I now spend half of my waking life talking with my co-workers, and I have no idea what any of their writing looks like. Same for the subset of my friends who don’t happen to send birthday cards. One of my best friends is getting married next year, and I have never seen her fiancé’s handwriting. How am I supposed to know whether he tends toward deduction or intuition, whether he’s intelligent or socially interested, whether he’s an artist or a serial killer?

Let me be clear: Graphology is, as Thornton told me, “complete B.S.” Very few innate factors influence a person’s penmanship. Neither legibility nor messiness indicates intelligence. (Both claims have been made.) Handwriting can be used to diagnose conditions that affect a person’s movements, such as Parkinson’s, but you can’t learn anything about a person’s moral fiber by how they cross their t’s. What you can learn is how that person has been socialized to present themselves to the world, says Seth Perlow, an associate English professor at Georgetown. Doctors have a culture of sloppy writing; teen girls have a culture of dotting their i’s with tiny hearts. Girls don’t write that way because they’re feminine; they write that way because they’ve learned that tiny hearts are associated with femininity.

[Read: How the ballpoint pen killed cursive]

I remember practicing my letters as a kid when I got bored in class, adjusting the parts I didn’t like, adding and removing the belts from my 7s, the caps from my a’s. Testing out a new style was like trying on a new outfit in front of a mirror—assessing how it looked, knowing other people would see it too. Now, as handwriting becomes less and less enmeshed in our daily lives, Thornton told me, “there’s good reason to think this is not an arena for self-expression. It’s just something you have to learn and get away with as best you can.” If you want to assert your identity, and you want people to see it, you’re more likely to do so by sculpting your appearance, adding your pronouns to your Instagram bio, or updating LinkedIn so everyone knows you’re a merchant without having to decipher your chicken scratch.

In fact, many of the qualities that were once conveyed with a certain type of handwriting—literary bent or emotional openness, for example—may now be conveyed by the act of putting pen to paper at all. Perlow has studied the practice of posting photos of handwritten poems on Instagram, and he told me that it “conjures a feeling of personal authenticity or expressiveness or direct contact with the personality of the poet.”

Tech companies have even tried to sell that feeling, in the form of computer-generated “handwriting.” Services such as Handwrytten, Simply Noted, and Pen Letters allow customers to type out a message that a robot will then transcribe, using an actual pen, in any number of “handwriting” styles. (The robot-written letter is then mailed on your behalf.) But these tools run the risk of conjuring less a sense of personal authenticity than one of inconsiderate laziness. If a friend or family member sent me one of these cards, I’d be annoyed that they didn’t put in the time, or the work, to write out a message with their own, human hand.

[From the October 2022 issue: Gen Z never learned to read cursive]

Perhaps that’s really what handwriting comes down to in the digital age: time and work. My husband and I write letters to each other a few times every year, and it’s a grueling act of love. Figuring out what I want to say is an emotional and intellectual project. But after a few paragraphs, the challenge becomes mostly physical. The muscles of my right palm start to cramp up; my ring finger aches from where I rest the pen against it. I’d like to think my determination to write through the discomfort says more about me than the script I settled on a decade ago.

How Lifeguards Lost Their Luster

2023-06-09T09:06:24-04:00

The United States, you may have heard, is in a lifeguard shortage. The city of Houston is offering new lifeguards a $500 bonus. Jackson, Mississippi, is raising lifeguard pay by more than 40 percent. Colorado is “stepping up” with $250,000 for hiring lifeguard reinforcements; in the meantime, senior citizens are filling in. According to the American Lifeguard Association, about half of the nation’s public pools will have to close or reduce their hours this summer because of a lack of staff.

The current shortage can be largely blamed on pandemic-era closures and work restrictions, according to news reports. But if that accounts for this year’s shortage as well as those reported in 2020, 2021, and 2022, it cannot explain the national lifeguard shortages of 2018, 2016, or 2012. Or, for that matter, a reported lifeguard shortage in 1984. Or 1951. Or 1926.

These crises—and the newspaper stories that describe them—are as much a summer tradition as boardwalks and ice cream. Local or national news articles on the subject have appeared in May or June of every single year of the 21st century. Hundreds more specimens of this perennial have been published since the 1930s. Each lays out the same basic claims: The swimming season might be compromised; drownings could increase. But few acknowledge that such claims were also made the year before, and in all the years before that. Indeed, the specter of a long, unguarded summer has haunted us for five generations now, about as long as there have been formally trained lifeguards in America.

The reasons given for the shortages have varied with the times. Now, of course, we have COVID. In the 1980s, authorities blamed Gen X demographics: “It’s happening because there simply aren’t as many 16-year-olds,” one told The New York Times. In the 1950s, they blamed the IRS: “Many lifeguards quit before earning $600 so their fathers can claim them as income tax dependents,” explained the Minneapolis Star Tribune. In the 1940s, experts said that the draft had roped in so many of the nation’s young men that, per The Baltimore Sun, some beaches and pools were “seriously considering employing women.” And in the 1930s, the shortage was attributed to the absorption of potential lifeguards into the Works Progress Administration.

But overall, the purported causes of shortages are remarkably repetitive and, in many cases, remarkably ahistoric.

The stringent requirements of lifeguarding—taking and paying for a multiday course to pass a tough physical exam—are a recurring scapegoat. So is low pay. In 1941, pool managers complained that young men who hadn’t been drafted could make much more working in defense industries than as a lifeguard. In 2007, a New Jersey lifeguard captain lamented to the Times that “iPods and cellphones are expensive … If kids are looking for the highest-paying job, it isn’t likely to be lifeguarding.” In that same article, a Connecticut parks official blamed the growing emphasis on career-building (and the concurrent rise of internships). The YMCA’s water-safety specialist also cited internships, in 2021. Any time unemployment is low, someone accuses it of contributing to the lifeguard shortage.

By far the most consistent explanations over the years can best be described as “kids these days.” See 1987: “The kids around here have too much money.” And 2015: “There is another big turnoff: having a phone on the lifeguard stand is a firing offense.” And 2019: “Some [teens] are even frightened of the lifesaving responsibility the job carries.” And 2022: “People just don’t want to do this kind of job.” And 2023: “Since COVID, people don’t want to work.” Wyatt Werneth, the national spokesperson for the American Lifeguard Association, told me this week that, after the pandemic arrived, people who might otherwise be lifeguard candidates began opting for jobs that could be done at home, such as “the influencing and social media and stuff like that.”

And then, of course, there’s the biggest problem of all: No one looks up to lifeguards anymore. From The New York Times in 1984: “Lifeguards were once authority figures, just like teachers once were. But the glory of the authoritarian age is gone.” In 1985, the Times wistfully recalled the lifeguard-loving cinema of the ’50s and ’60s (Beach Blanket Bingo and its ilk) and the reverence it once inspired. Robert A. Kerwin, the water-safety coordinator of the New Jersey State Division of Parks and Forestry, told the paper, “The day of the macho lifeguard sitting in the chair flexing his muscles is finished. For one thing, 25 percent of our guards are girls.” (For what it’s worth, Newspapers.com lists plenty of articles about lifeguard shortages from the ’50s and the ’60s too.)

[Read: Imagining the jellyfish apocalypse]

The Times once declared, “The lifeguard is an endangered species.” But its population recovered briefly in the 1990s, thanks to David Hasselhoff. “When I became a lifeguard,” Werneth said, “we had Baywatch, and everybody wanted to be a lifeguard. They wanted that lifestyle where you had helicopters and you had fast boats and beautiful people, and you’re saving lives.” But Baywatch: Hawaii ceased production in 2001, and after that, Werneth told me, “things started declining.” Lifeguard employment took a dip and then a swan dive starting in 2020. “I can almost call it a ground zero,” Bernard Fisher, the director of the American Lifeguard Association, said of the shortage in a 2022 Fox News article.

Despite the tenor of that analogy (Fisher also compared the lack of lifeguards to the lack of baby formula), drowning rates haven’t really spiked. In fact, they’re now a third of what they were in 1970, and have been dropping steadily for a century or more. (There was a very slight uptick in 2020 and 2021, the most recent years for which data are available.) In other words, the many lifeguard crises of the past—or perhaps the single, never-ending one—have not correlated with any widespread drowning crises in America. That does not mean that lifeguard shortages are fake, but hard data on their scope remain obscure. Werneth told me that the American Lifeguard Association receives “very sporadic” reports from pools, parks, and beaches, and has just a rough sense of the level of need in different regions.

But if the lifeguard is once again an endangered species, it’s still beloved: more like a giant panda than a Gerlach’s cockroach. As a culture, we do still think of lifeguards as sexy, heroic, and essential (if not authoritarian). Baywatch may be off the air, but it’s always coming back.

23 Pandemic Decisions That Actually Went Right

2023-05-09T12:58:16-04:00

More than three years ago, the coronavirus pandemic officially became an emergency, and much of the world froze in place while politicians and public-health advisers tried to figure out what on Earth to do. Now the emergency is officially over—the World Health Organization declared so on Friday, and the Biden administration will do the same later this week.

Along the way, almost 7 million people died, according to the WHO, and looking back at the decisions made as COVID spread is, for the most part, a demoralizing exercise. It was already possible to see, in January 2020, that America didn’t have enough masks; in February, that misinformation would proliferate; in March, that nursing homes would become death traps, that inequality would widen, that children’s education, patients’ care, and women’s careers would suffer. What would go wrong has been all too clear from the beginning.

Not every lesson has to be a cautionary tale, however, and the end of the COVID-19 emergency may be, if nothing else, a chance to consider which pandemic policies, decisions, and ideas actually worked out for the best. Put another way: In the face of so much suffering, what went right?

To find out, we called up more than a dozen people who have spent the past several years in the thick of pandemic decision making, and asked: When the next pandemic comes, which concrete action would you repeat in exactly the same way?

What they told us is by no means a comprehensive playbook for handling a future public-health crisis. But they did lay out 23 specific tactics—and five big themes—that have kept the past few years from being even worse.

Good information makes everything else possible.

Start immediate briefings for the public. At the beginning of March 2020, within days of New York City detecting its first case of COVID-19, Governor Andrew Cuomo and Mayor Bill de Blasio began giving daily or near-daily coronavirus press briefings, many of which included health experts along with elected officials. These briefings gave the public a consistent, reliable narrative to follow during the earliest, most uncertain days of the pandemic, and put science at the forefront of the discourse, Jay Varma, a professor of population health at Cornell University and a former adviser to de Blasio, told us.
Let everyone see the information you have. In Medway, Massachusetts, for instance, the public-school system set up a data dashboard and released daily testing results. This allowed the entire affected community to see the impact of COVID in schools, Armand Pires, the superintendent of Medway Public Schools, told us.
Be clear that some data streams are better than others. During the first year of the pandemic, COVID-hospitalization rates were more consistent and reliable than, say, case counts and testing data, which varied with testing shortages and holidays, Erin Kissane, the managing editor of the COVID Tracking Project, told us.The project, which grew out of The Atlantic’s reporting on testing data, tracked COVID cases, hospitalizations, and deaths. CTP made a point of explaining where the data came from, what their flaws and shortcomings were, and why they were messy, instead of worrying about how people might react to this kind of information.
Act quickly on the data. At the University of Illinois Urbana-Champaign, testing made a difference, because the administration acted quickly after cases started rising faster than predicted when students returned in fall of 2020, Rebecca Lee Smith, a UIUC epidemiologist, told us. The university instituted a “stay at home” order, and cases went down—and remained down. Even after the order ended, students and staff continued to be tested every four days so that anyone with COVID could be identified and isolated quickly.
And use it to target the places that may need the most attention. In California, a social-vulnerability index helped pinpoint areas to focus vaccine campaigns on, Brad Pollock, UC Davis’s Rolkin Chair in Public-Health Sciences and the leader of Healthy Davis Together, told us. In this instance, that meant places with migrant farmworkers and unhoused people, but this kind of precision public health could also work for other populations.
Engage with skeptics. Rather than ignore misinformation or pick a fight with the people promoting it, Nirav Shah, the former director of Maine’s CDC, decided to hear them out, going on a local call-in radio show with hosts known to be skeptical of vaccines.

A pandemic requires thinking at scale.

Do pooled testing as early as possible. Medway’s public-school district used this technique, which combines samples from multiple people into one tube and then tests them all at once, to help reopen elementary schools in early 2021, said Pires, the Medway superintendent. Pooled testing made it possible to test large groups of people relatively quickly and cheaply.
Choose technology that scales up quickly. Pfizer chose to use mRNA-vaccine tech in part because traditional vaccines are scaled up in stainless-steel vats, Jim Cafone, Pfizer’s senior vice president for global supply chain, told us. If the goal is to vaccinate billions of patients, “there’s not enough stainless steel in the world to do what you need to do,” he said. By contrast, mRNA is manufactured using lipid nanoparticle pumps, many more of which can fit into much less physical space.
Take advantage of existing resources. UC Davis repurposed genomic tools normally used for agriculture for COVID testing, and was able to perform 10,000 tests a day, Pollock, the UC Davis professor, told us.
Use the Defense Production Act. This Cold War–era law, which allows the U.S. to force companies to prioritize orders from the government, is widely used in the defense sector. During the pandemic, the federal government invoked the DPA to break logjams in vaccine manufacturing, Chad Bown, a fellow at the Peterson Institute for International Economics who tracked the vaccine supply chain, told us. For example, suppliers of equipment used in pharmaceutical manufacturing were compelled to prioritize COVID-vaccine makers, and fill-and-finish facilities were compelled to bottle COVID vaccines first—ensuring that the vaccines the U.S. government had purchased would be delivered quickly.

Vaccines need to work for everyone.

Recruit diverse populations for clinical trials. Late-stage studies on new drugs and vaccines have a long history of underrepresenting people from marginalized backgrounds, including people of color. That trend, as researchers have repeatedly pointed out, runs two risks: overlooking differences in effectiveness that might not appear until after a product has been administered en masse, and worsening the distrust built up after decades of medical racism and outright abuse. The COVID-vaccine trials didn’t do a perfect job of enrolling participants that fully represent the diversity of America, but they did better than many prior Phase 3 clinical trials despite having to rapidly enroll 30,000 to 40,000 adults, Grace Lee, the chair of CDC’s Advisory Committee on Immunization Practices, told us. That meant the trials were able to provide promising evidence that the shots were safe and effective across populations—and, potentially, convince wider swaths of the public that the shots worked for people like them.
Try out multiple vaccines. No one can say for sure which vaccines might work or what problems each might run into. So drug companies tested several candidates at once in Phase I trials, Annaliesa Anderson, the chief scientific officer for vaccine research and development at Pfizer, told us; similarly, Operation Warp Speed placed big bets on six different options, Bown, the Peterson Institute fellow, pointed out.
Be ready to vet vaccine safety—fast. The rarest COVID-vaccine side effects weren’t picked up in clinical trials. But the United States’ multipronged vaccine-safety surveillance program was sensitive and speedy enough that within months of the shots’ debut, researchers found a clotting issue linked to Johnson & Johnson, and a myocarditis risk associated with Pfizer’s and Moderna’s mRNA shots. They were also able to confidently weigh those risks against the immunizations’ many benefits. With these data in hand, the CDC and its advisory groups were able to throw their weight behind the new vaccines without reservations, said Lee, the ACIP chair.
Make the rollout simple. When Maine was determining eligibility for the first round of COVID-19 vaccines, the state prioritized health-care workers and then green-lighted residents based solely on age—one of the most straightforward eligibility criteria in the country. Shah, the former head of Maine’s CDC, told us that he and other local officials credit the easy-to-follow system with Maine’s sky-high immunization rates, which have consistently ranked the state among the nation’s most vaccinated regions.
Create vaccine pop-ups. For many older adults and people with limited mobility, getting vaccinated was largely a logistical challenge. Setting up temporary clinics where they lived—at senior centers or low-income housing, as in East Boston, for instance—helped ensure that transportation would not be an obstacle for them, said Josh Barocas, an infectious-diseases doctor at the University of Colorado School of Medicine.
Give out boosters while people still want them. When boosters were first broadly authorized and recommended in the fall of 2021, there was a mad rush to immunization lines. In Maine, Shah said, local officials discovered that pharmacies were so low on staff and supplies that they were canceling appointments or turning people away. In response, the state’s CDC set up a massive vaccination center in Augusta. Within days, they’d given out thousands of shots, including both boosters and the newly authorized pediatric shots.

Also, spend money.

Basic research spending matters. The COVID vaccines wouldn’t have been ready for the public nearly as quickly without a number of existing advances in immunology, Anthony Fauci, the former head of the National Institute of Allergy and Infectious Diseases, told us. Scientists had known for years that mRNA had immense potential as a delivery platform for vaccines, but before SARS-CoV-2 appeared, they hadn’t had quite the means or urgency to move the shots to market. And research into vaccines against other viruses, such as RSV and MERS, had already offered hints about the sorts of genetic modifications that might be needed to stabilize the coronavirus’s spike protein into a form that would marshal a strong, lasting immune response.
Pour money into making vaccines before knowing they work. Manufacturing millions of doses of a vaccine candidate that might ultimately prove useless wouldn’t usually be a wise business decision. But Operation Warp Speed’s massive subsidies helped persuade manufacturers to begin making and stockpiling doses early on, Bown said. OWS also made additional investments to ensure that the U.S. had enough syringes and factories to bottle vaccines. So when the vaccines were given the green light, tens of millions of doses were almost immediately available.
Invest in worker safety. The entertainment industry poured a massive amount of funds into getting COVID mitigations—testing, masking, ventilation, sick leave—off the ground so that it could resume work earlier than many other sectors. That showed what mitigation tools can accomplish if companies are willing to put funds toward them, Saskia Popescu, an infection-prevention expert in Arizona affiliated with George Mason University, told us.

Lastly, consider the context.

Rely on local relationships. To distribute vaccines to nursing homes, West Virginia initially eschewed the federal pharmacy program with CVS and Walgreens, Clay Marsh, West Virginia’s COVID czar, told us. Instead, the state partnered with local, family-run pharmacies that already provided these nursing homes with medication and flu vaccines. This approach might not have worked everywhere, but it worked for West Virginia.
Don’t shy away from public-private partnerships. In Davis, California, a hotelier provided empty units for quarantine housing, Pollock said. In New York City, the robotics firm Opentrons helped NYU scale up testing capacity; the resulting partnership, called the Pandemic Response Lab, quickly slashed wait times for results, Varma, the former de Blasio adviser, said.
Create spaces for vulnerable people to get help. People experiencing homelessness, individuals with substance-abuse disorders, and survivors of domestic violence require care tailored to their needs. In Boston, for example, a hospital recuperation unit built specifically for homeless people with COVID who were unable to self-isolate helped bring down hospitalizations in the community overall, Barocas said.
Frame the pandemic response as a social movement. Involve not just public-health officials but also schools, religious groups, political leaders, and other sectors. For example, Matt Willis, the public-health officer for Marin County, California, told us, his county formed larger “community response teams” that agreed on and disseminated unified messages.

Beware the Ozempic Burp

2023-05-02T14:05:40-04:00

On the November morning when the sulfur burps began, Derron Borders was welcoming prospective students at the graduate school where he works in New York. Every few minutes, no matter how hard he tried to stop, another foul-smelling cloud escaped his mouth. “Burps that taste and smell like rotten eggs—I think that’s what I typed in Google,” he told me.

Eventually, Borders learned that his diabetes medication was to blame. Sulfur burps appear to be a somewhat rare side effect of semaglutide, tirzepatide, and other drugs in their class, known as GLP-1 receptor agonists. Over the past several years, these medications have become more popular under the brand names Ozempic, Wegovy, and Mounjaro, as a diabetes treatment and a weight-loss drug. And as prescription numbers rise, a strange and unpleasant side effect has been growing more apparent too.

GLP-1 receptor agonists are well known to cause gastrointestinal symptoms, including abdominal pain, diarrhea, and vomiting. In clinical trials of semaglutide for weight loss, 44 percent of participants experienced nausea and 31 percent had diarrhea. (The same conditions afflicted only about one-sixth of participants who received a placebo.) Burping, a.k.a. “eructation,” showed up in about 9 percent of those who got the drug, versus less than 1 percent of those who took a placebo. The FDA lists eructation as a possible side effect for semaglutide and tirzepatide alike.

But I couldn’t find any information in the clinical-trial reports or FDA fact sheets about sulfur burps in particular, and neither Novo Nordisk nor Eli Lilly, the companies that make these drugs, responded to my inquiries. Laura Davisson, the director of medical weight management at West Virginia University Health Sciences, told me that more than 1,000 of her clinic’s patients are currently on a GLP-1 receptor agonist, and about one-fifth experience sulfur burps at first. For all but a handful of these patients, she said, the issue goes away after a few months. Holly Lofton, an obesity-medicine specialist at NYU, guesses that it affects just 2 percent of her patients.

Experts aren’t sure why taking GLP-1 receptor agonists might lead to having smelly burps, but they have some theories. Davisson proposed that semaglutide boosts the number of bacteria in patients’ digestive tracts that produce hydrogen sulfide, a gas that can be expelled from either end of the digestive tract, and that smells (as Borders found) like rotten eggs. She also noted that the drugs slow down digestion, which could give the stomach more time to break down food and produce gas. In this situation, Lofton told me, the putrid air may escape most readily up through the mouth, because it’s lighter than the liquids and semi-solids that also fill the stomach. “Whatever’s on top will come up,” she said.

[Read: We’ve had a cheaper, more potent Ozempic alternative for decades]

Eating more than usual while on the medications seems to be a common trigger. Davisson said that certain foods, such as dairy, may also lead to more odorous emissions. “Sometimes it’s a matter of trial and error,” she said. “Some tips that we give people are things like: Don’t eat really heavy meals; don’t eat large portions at once; don’t eat right before bed.” In addition to these behavioral approaches, Craig Gluckman, a gastroenterologist at UCLA Health, told me he recommends antacids and anti-gas medications to patients with GLP-1-agonist-related sulfur burps. (Online, apple-cider vinegar is commonly recommended as a fix, but Gluckman said he would not recommend it.)

The providers I spoke with said that, in general, patients tend to experience sulfur burps when they’re first starting an Ozempic-like drug, or raising their dose. That was the case for Crystal Garcia, an HR administrator in Texas who started taking semaglutide from a compounding pharmacy after her doctor told her she was prediabetic. (Garcia vlogs about her experience with weight-loss drugs.) Three months later, while out to breakfast at a restaurant, Garcia's family started to complain about a gross and eggy smell. Garcia figured that the smell was coming from the food, but it lingered in the car after the meal. The family wondered whether Garcia’s young son had had an accident. “I was like, it could not be me. There’s no way,” she told me. But when she burped again, she was forced to change her mind.

Many patients are unaware that sulfur burps are a possible side effect of their medication until they start, well, burping sulfur. For a while, Borders had no idea that his diabetes medicine might be the culprit; when he saw a physician’s assistant to discuss his issue, “Ozempic didn’t even come up,” he said. The side effect is relatively new to physicians. Earlier GLP-1 agonists didn’t seem to produce sulfur burps so frequently, Lofton said. In her practice, the phenomenon wasn't really apparent until Ozempic hit the American market in 2018, and even then, she learned about it only from her patients. “I’d never heard of sulfur burps before I started prescribing this medicine,” she said.

[Read: Ozempic is about to be old news]

Though the sulfur burps are (physically) harmless, some patients do stop taking their diabetes or weight-loss drugs because of them, Lofton told me. But most, including Garcia and Borders, end up sticking with their program. As bad as the side effects may be, patients think the drugs’ benefits are worth it. “I have had a patient say that her burps smelled like poop,” Davisson said. But even then, she did not want to stop the medication.

Inside the Mind of an Anti-Paxxer

2022-11-22T09:56:14-05:00

Updated at 2:30 p.m. ET on November 25, 2022

Paxlovid is a paradoxlovid. The game-changing antiviral swooped in during the pandemic’s worst winter with the promise of slowing COVID deaths to a trickle. But since it became widely available this spring, death rates have hardly budged.

According to the White House, the problem is not the drug but the fact that too few people are taking it. A recent CDC report found that from April to July, less than one-third of America’s 80-plus-year-olds with COVID ended up taking Paxlovid, even though they had the most to gain from doing so. What gives? Some Americans may be having trouble accessing Paxlovid, but clearly, a significant proportion of patients and doctors are just saying no to antiviral drugs. There are no national statistics on Paxlovid refusal, so I talked with physicians around the country to learn more about their motivations. Who are the anti-Paxxers, and how dangerous is their dogma?

First things first: Paxlovid hesitancy does seem to be political, but that’s not the whole story. As a rule, fewer prescriptions of the drug are given out per capita in red states than in blue ones: Wyoming, for example, appears to be the nation’s leading anti-Paxxer state, with just one course of treatment given out for every 125 residents; in Rhode Island, the most Pax-enthusiastic state, it’s one in 28. (I’m using courses of treatment per capita rather than per COVID case because of the general unreliability of case data these days and differences in testing and reporting practices among states.)

Still, clinicians working in deep-red parts of the country told me that, on this matter at least, their patients are not significantly divided by politics. “Republicans and Democrats both love Paxlovid,” says Jason Bronner, the medical director of primary care at St. Luke’s Medical System, in Idaho. Some 20 to 30 percent of his COVID patients decline to take the drug, he told me, but they don’t appear to be driven by the same polarized attitudes he sees around vaccines. Jessica Kalender-Rich, a geriatrician at the University of Kansas Health System, told me that she still gets occasional requests for ivermectin, and that some of her patients insist that COVID is a hoax. But the ones who outright refuse Paxlovid are not obsessing over microchips or government overreach. Instead, they mostly tell her that they’re worried about treatment side effects and rebound infections of the virus.

Rebound COVID came up again and again when I asked doctors why their patients are hesitant to take Paxlovid. The link between the drug and a return of symptoms after an initial recovery has been the subject of much concern and debate since the spring; just last week, researchers reported in a study that has not yet been peer-reviewed that symptom rebound is more than twice as common among Paxlovid takers than among those who decline it. The fact that so many prominent figures in the federal government—including President Joe Biden, First Lady Jill Biden, CDC Director Rochelle Walensky, and White House Chief Medical Adviser Anthony Fauci—have now had rebound certainly doesn’t help inspire confidence. One of Kalender-Rich’s patients specifically cited Fauci’s experience when refusing the drug. (The next day, the patient felt worse and accepted a prescription.)

[Read: Of course Biden has rebound COVID]

Rebound may not be dangerous, but you have to admit that it doesn’t sound like a good time. “People will say, ‘I’d rather be really sick for four or five days than just kind of sick for two weeks,’” says Adam Fiterstein, the chief of urgent care at the New York medical network ProHealth. The threat of rebound might be especially scary for geriatric patients and their family, because it means spending more time alone. “For some of these older adults, that isolation time is actually way worse than the virus at this point in the pandemic,” Kalender-Rich said. Paxlovid mouth—a bitter, metallic taste that can last throughout the course of treatment—can also be a concern for the elderly, who may already suffer from lack of appetite or other issues that restrict their eating.

Drug interactions are another source of worry for the anti-Paxxers. Official COVID-treatment guidelines warn that the antiviral may have ill effects when combined with any of more than 100 other medications. Geriatric patients in particular might need to tweak their daily regimens of pills while under treatment with Paxlovid, Kalender-Rich told me. That’s hardly ever a problem medically, she said, but some people are still reluctant to make the change, especially if a previous doctor told them to never, ever skip a dose.

These potential downsides are extra salient for people who don’t fear COVID like they used to. The patients who refuse Paxlovid are the ones who are doing well, Bronner said: “They don’t feel totally sick and are not scared like they were in previous waves.” Hundreds of Americans are still dying daily from COVID, but any given community might have seen only a handful of severe cases and deaths since the spring. Many patients “don’t feel like they need to take a medicine, because their neighbor was fine,” Kalender-Rich said.

[Read: Paxlovid mouth is real—and gross]

Doctors too can be anti-Paxxers. Hans Duvefelt, a primary-care physician in rural Maine, won’t prescribe Paxlovid to his patients. He told me via email that he avoids it on account of rebound risk, side effects, kidney concerns, and drug interactions. “Paxlovid is an inferior choice,” he said, when compared with molnupiravir, another COVID antiviral. To be clear, the data on preventing hospitalization and death have been less impressive for molnupiravir than Paxlovid. Also, a June preprint found that patients treated with molnupiravir rebounded at least as often as those treated with Paxlovid. Duvefelt did not respond to follow-up questions, so I couldn’t ask him about these data.

Other doctors believe in the good Paxlovid can do but still struggle with the decision to prescribe. “This is a much more nuanced risk-benefit discussion than giving somebody amoxicillin for strep throat,” Jeremy Cauwels, the chief physician at Sanford Health in South Dakota, told me. “If you’re looking at that as an ER doctor, who by definition has no follow-up with the patient, it’s very hard to say, ‘I’m going to give you a drug that interacts with lots of medications.’” Persistent uncertainty about exactly how much Paxlovid helps people who are up to date on their COVID shots doesn’t help.

Regardless of what’s causing Paxlovid hesitancy, the exact stakes are difficult to define. Last month, Ashish Jha, the Biden administration’s COVID-19 response coordinator, told The New York Times that daily deaths from the pandemic could drop by almost 90 percent if every COVID patient over the age of 50 were treated with Paxlovid or monoclonal antibodies. The doctors I spoke with mostly didn’t dispute this; Kalender-Rich said she “would believe a number closer to 75 percent” but agreed with the general sentiment. That said, none of the doctors I spoke with could point me toward any specific cases where one of their patients refused Paxlovid only to end up severely ill or dead. And no one knows how many deaths could be reduced specifically by attacking anti-Paxxer beliefs as opposed to, say, removing barriers to access and encouraging more testing.

Because anti-Paxxerism appears to be less organized and ideological than anti-vaxxerism, some favored strategies to combat the latter—targeting influencers on social media, for example—might not work. The doctors I spoke with said that the best venue for changing minds is the exam room. “It really comes down to a face-to-face conversation” about the risks and benefits of the drug, Cauwels said: “Our patients still trust us enough to have that conversation.”

Pax-hesitant providers, on the other hand, may just need a bit more time to feel convinced that the drug is safe and effective when used correctly; some may be waiting on more data from large, randomized clinical trials. “Across different parts of the country, adoption of new things is always going to be slower,” Kalender-Rich said. That’s not exactly a comforting thought when hundreds of people are still dying every day, but it does suggest, at the very least, that we have something to look forward to.

This article originally implied, incorrectly, that clinical trials have directly compared the efficacy of molnupiravir to that of Paxlovid.

A Simple Rule for Planning Your Fall Booster Shot

2022-08-27T08:00:00-04:00

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

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

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

If you haven’t had an Omicron infection:

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

[Read: The pandemic’s soft closing]

If you have had an Omicron infection:

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

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

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

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

If you had an Omicron infection this summer:

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

If you’re at high risk:

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

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

If you want to wait and see:

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

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

Of Course Biden Has Rebound COVID

2022-07-30T15:40:12-04:00

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.

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.

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.

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.

Monkeypox Could Be Nothing—Or It Could Be the Next Syphilis

2022-06-09T14:57:06-04:00

The first reports of monkeypox cases in Europe began to surface in mid-May. A week later, there were 92 confirmed cases outside the Central and West African countries where the disease usually circulates; now there are 1,200. By the end of this month, who knows? “If you’d asked me two weeks ago, I would have anticipated that there might be a few thousand cases globally related to this current outbreak” before it ended, Jay Varma, a population-health professor at Weill Cornell Medical College, told me. “But I’ve become much more pessimistic.”

Where, exactly, is the outbreak headed? When I asked five experts for their predictions, they would say only one thing for certain: Monkeypox is not the next COVID-19. It’s simply not transmissible enough to cause infections on the scale of the pandemic, nor does it seem to be a particularly deadly virus. (None of the 1,200 patients has died so far.) But beyond that, their views ranged widely: The outbreak may be over before we know it; or it might become a modest, intermittent problem; or it could transform into an ever-present risk and inconvenience, like the next genital herpes. Here are three possible paths monkeypox could take.

The Rosy Scenario: A Quick Fizzle

This is not the first time monkeypox has entered the United States. At least 47 people in six states fell ill from the virus in 2003 after interacting with infected pet prairie dogs (legal to own in most states!). The spread was contained within a couple of months, and nobody died; two people got seriously sick, but they recovered.

[Read: We should have seen monkeypox coming]

This time around, prairie dogs are not involved. Most, if not all, of this year’s monkeypox cases in the U.S. appear to have resulted from person-to-person contact. That makes the public-health response more complicated than euthanizing potentially infected animals, as officials did in 2003. We might still quash the spread quickly through immunization, Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, told me. After all, the U.S. has a stockpile of smallpox vaccines on hand that would also work against this outbreak. (The exact size of the stockpile remains unclear.) “Monkeypox is a containable virus,” he told me.

The 2003 outbreak was brought to heel, in part, through a tactic called ring vaccination, in which the close contacts of an infected patient are all inoculated. This works because contact tracing for monkeypox is relatively easy thanks to the physical proximity necessary for its transmission, and because vaccinating someone who has recently been infected can keep them from becoming contagious. Adalja predicts that ring vaccination will likely outpace the spread of monkeypox in the U.S. in a matter of weeks, and that cases will fall to zero within about three months.

The Medium Scenario: A Sporadic Problem

Monkeypox already breaks out from time to time in Central and West Africa. Experts say that’s because the virus is endemic in local animal populations, probably some kind of mammal. The same could happen here in the U.S.: If enough American wildlife get infected through interactions with infected humans, then monkeypox could circulate in silence after human cases drop to zero. Every so often, an animal would infect a person, that person would spread the virus to some close contacts, and another minor outbreak would form, then fizzle out. Repeat indefinitely.

Bhargavi Rao, who worked in the Democratic Republic of Congo and the Central African Republic as the head of emerging and infectious diseases at Doctors Without Borders, told me that a spate of monkeypox infections is “not the sort of thing that overwhelms a community.” She said she thinks the risk of monkeypox becoming endemic in animals outside Central and West Africa is “very low,” but if it did, its effects would be akin to those of modern anthrax, rabies, or bird flu; that is, it might cause occasional disruption and lead to occasional culling of animals, but it wouldn’t generally affect daily life. (James Diaz, the director of environmental and occupational health at Louisiana State University, told me that he suspects monkeypox might already be endemic in American wildlife—but also that there’s no hard evidence to support this claim.)

The fact that many recent cases have been recorded in and around big cities could lead to different outcomes, though. In the countries where Rao worked, the disease mostly jumps from wildlife to farmers and bush hunters who live in isolated communities. She said there’s no way of knowing how big an outbreak might get in an American metropolis, even as those at risk would generally have better access to testing and vaccines. If the outbreak were big enough, the virus might become endemic in rodent populations, causing further urban outbreaks down the line. “When it’s in the rats, there’s nothing you can do,” Adalja told me.

The Bad Scenario: Another Syphilis

We’ll be dealing with something entirely different if the current outbreak can’t be stopped. Both Rao and Adalja said such an outcome seems unlikely because monkeypox patients are generally not infectious before they’re symptomatic, and the world already has tests, vaccines, and treatments for the virus. But the conventional wisdom about monkeypox might not hold for this outbreak. Varma, who helped lead New York City’s response to COVID, is much more worried than the other experts I spoke with. “I would say it’s less than 50 percent probability that we will contain this,” he said.

That’s not to say that one-third of the country is likely to come down with monkeypox in the next six months. Varma predicts that monkeypox will continue to circulate at low levels and stay concentrated in the community of men who have sex with men. (To be clear, monkeypox is not a sexually transmitted infection. The CDC has said that “a high number” of cases so far have involved men who have sex with men, but the disease can be spread through sexual or nonsexual contact between anyone.) If that’s what happens, then monkeypox would be similar to syphilis, Varma said, which affects about 0.04 percent of Americans, most of them men who have sex with men. In Varma’s absolute worst-case scenario—which he thinks is less likely—monkeypox could spread through all sorts of communities, including children and pregnant women, and become as common as genital herpes, with more than 12 percent of Americans infected.

Jim Downs[: Gay men need a specific warning about monkeypox]

Again, this would not spell civilizational collapse. Very few people who contract monkeypox die from it or get seriously sick. Even if monkeypox did become widespread among the American population, Adalja told me, routine vaccination could eliminate much of the associated risks to people’s health. But the more people who get sick, the greater the likelihood that someone will experience a rare and serious complication. Population-scale vaccination, too, could have some downsides.

We also don’t know how the disease will change. DNA viruses, including monkeypox, are generally stable, and evolve into new strains slowly. But “it’s never a good thing to let a zoonotic virus spread unchecked in humans,” Boghuma Titanji, an infectious-disease specialist at Emory University, told me. “The reality is you do not know what the adaptation of that virus in a new host will do.” It could become more or less transmissible, more or less capable of causing serious disease and death. Or it could stay pretty much the same.

No one will be able to accurately forecast the future of this outbreak until we’re certain of the present. And we’re just not there yet. The virus’s incubation period averages one to two weeks, but can stretch as long as three, which means the cases we’re seeing now reflect the spread of the virus many days ago. We’re also not testing enough to keep track of the outbreak, Titanji told me.

Testing is especially important because cases in the current outbreak look so different from classical monkeypox. Historically, monkeypox lesions developed around the tongue and mouth first, followed by a rash on the face, arms, and legs, which progressed into lesions; those symptoms were easy to see. The recent outbreak, however, has included many patients who have only a handful of lesions, concentrated around their genitalia and anus. In the past, U.S. cases of monkeypox were travel-related, and people who fell ill showed up to travel clinics or told their doctor they’d been out of the country; now patients might show up at sexual-health clinics to investigate the scabs on their private parts. The more accessible testing is, the easier it will be for patients to be identified and advised to isolate, while vaccines are provided to their contacts. “The sooner you can get a lab-confirmed infection, the sooner people take it seriously,” Varma said.

For now, we still don’t know how many people around the country are infected, nor how many others will eventually get sick. When I asked Titanji how and when we’ll know which path we’re on, she said it’s difficult to tell, and not worth guessing. “Every time a virus crosses species and gets into a new species, and it’s transmitting itself and causing outbreaks, you are in a gray zone.”

Rebound COVID Is Just the Start of Paxlovid’s Mysteries

2022-05-26T09:48:09-04:00

The first data on Paxlovid, out last November, hinted that the COVID antiviral would cut the risk of hospitalization and death by 89 percent. Pundits called the drug “a monster breakthrough,” “miraculous,” and “the biggest advance in the pandemic since the vaccines.” “Today’s news is a real game-changer,” said Albert Bourla, the CEO of Pfizer, which makes the drug. The pills are “a game changer,” President Joe Biden repeated a few months later.

Now, finally, the game is being changed. The government has ordered 20 million courses of Paxlovid, committing half of the $10 billion in additional COVID funding that is being negotiated in the Senate; and Pfizer says that the number of patients taking the drug increased by a factor of 10 between mid-February and late April.

But as the treatment spreads, so too does confusion over its effectiveness and side effects. Patients have complained of a bitter, metallic taste, or one like grapefruit juice mixed with soap, the whole time they were on the drug. More concerning, some have reported experiencing a second round of symptoms, and going back to testing positive, when the pills were done, a phenomenon that’s become known as “Paxlovid rebound.” Meanwhile, Pfizer has never published any final data on the use of the drug by vaccinated patients, leaving medical professionals with little information about how the drug works for people who have received their shots—which is to say, most of the adult population in the U.S. “We’re all riding on hope at this point,” Reshma Ramachandran, a family-medicine doctor at Yale, told me.

[Read: Paxlovid mouth is real—and gross]

An individual patient would never know if Paxlovid worked for them, because you could never say how sick you would have gotten if you hadn’t taken the pills. If the drug doesn’t really do that much for vaccinated people—if it fails to have meaningful effects on their risk of severe disease, and doesn’t help resolve their symptoms—then giving it out widely could be a waste of the dwindling resources the United States has committed to fight the pandemic, not to mention physicians’ time and patients’ sense of taste. And because people who have just recovered from COVID might reasonably believe they’re in the clear, and mingle with abandon, surprise cases of Paxlovid rebound could end up causing more transmission. “We continue to monitor data from our ongoing clinical studies and post-authorization safety surveillance,” a Pfizer spokesperson told me in an email, noting that cases of viral rebound “are being reported at a rate consistent with observations” from the company’s published clinical trial.

Taste disruption (a.k.a. dysgeusia) is the most straightforward of the Paxlovid mysteries, because any sudden onset of soapy-grapefruit-penny flavor can be attributed to the antiviral with a decent amount of confidence. In its only published trial of the drug, conducted in unvaccinated, high-risk patients, Pfizer found that 5.6 percent of Paxlovid-takers experienced dysgeusia, compared with 0.3 percent of those who got the placebo. If you apply that rate to the hundreds of thousands of people who have now received the drug, you might expect to see some tens of thousands of cases by now. Given how people like to kvetch on social media, that side effect could very well seem like it’s occurring in a lot more than one out of 18 patients. Perhaps all that’s going on here is that rare events seem common on a large scale. Perhaps! But I’ve heard from dozens of patients on the drug in the course of my reporting, and every single one told me that they’d suffered through at least mild dysgeusia. Paul Sax, the clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital, told me he suspects “way more than half” of the people who’ve taken Paxlovid have experienced the taste.

As for rebound, a Pfizer executive said during an earnings call this month that the company had taken a “preliminary look” at its trial data and concluded that viral loads bounced back up in about 2 percent of patients. He also said they saw “the same or close to the same percent in the placebo arm.” (These findings have not been published.) “Reports from the beginning of the pandemic suggested some participants exhibit fluctuations in nasal viral RNA, and these fluctuations could be a phenomena [sic] of the disease itself,” the Pfizer spokesperson told me. In any case, if you apply that measured rate of 2 percent to the population who have now taken the drug, you’d expect thousands of people to have experienced Paxlovid rebound by this point (and many, many more cases of rebound occurring among all the COVID patients who didn’t take it).

The real number is—well, we have pretty much no idea what the real number is. The federal government is not tracking Paxlovid rebound in any public-facing database, and the CDC released an advisory on Tuesday saying the agency doesn’t know whether a recurrence of symptoms can be connected to the drug. The agency also clarified that “Paxlovid continues to be recommended for early stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease” and that anyone who rebounds should isolate for another five days. No researchers have yet published studies measuring the prevalence of rebound, but a good number of clinicians and Paxlovid patients are convinced that it’s higher than 2 percent. “To trust that number would’ve been to not believe my eyes,” Bob Wachter, the chair of medicine at UC San Francisco, told me.

In an attempt to find some clarity, Wachter decided to poll his Twitter connections on whether they’d taken Paxlovid and rebounded. (I’m legally obligated to tell you that Twitter polls are neither scientific nor particularly reliable—which Wachter knows perfectly well.) Of the respondents who said they had taken Paxlovid, 45 percent rebounded; Wachter said he guesses the real proportion is closer to 10 or 20 percent. A few hours after we spoke, Wachter tweeted that his wife, who had recently finished a course of the antiviral and recovered from COVID, just tested positive again.

In short, Pfizer’s clinical-trial results may not be matching up with physicians’ and patients’ real-world experience. When I asked the company why, the spokesperson replied, “We cannot speculate on why some people may or may not experience dysgeusia, but we can reiterate that 5.6% of participants in a well-controlled clinical trial experienced that event compared to 0.3% in the placebo arm.” As for rebound, he said, the company continues to monitor the data but hasn’t yet seen any unexpected numbers. “We are actively reviewing but, thus far, have not seen an association with subsequent severe disease (i.e., hospitalization or death),” he added.

Discrepancies between the trial data and real-world experience might arise from the timing of the original research. Pfizer announced its results in early November, which means that participants received Paxlovid to help fight off infections caused by the Delta variant, which is naught but an unpleasant memory today. Three Omicron subvariants are currently floating through Americans’ airways. Perhaps one of them simply causes more rebound cases than Delta did, by keeping viral levels high enough that five days of antiviral therapy are not enough to wipe it out. Anthony Fauci announced last week that the National Institutes of Health is in talks with Pfizer to test out a longer course of Paxlovid to see if it reduces rates of rebound. (“We will share updates when we have them,” the Pfizer spokesperson said.) In the meantime, Bourla, Pfizer’s CEO, has suggested that those who experience a rebound should simply take another round of Paxlovid. But the FDA was less than enthusiastic about the idea.

Patients’ immunization status remains the most obvious difference between Pfizer’s published clinical trial and present-day reality. That study was conducted exclusively in unvaccinated participants who were at high risk of complications from COVID. The drug is now authorized for use in vaxxed and unvaxxed patients alike. Could this explain the apparent gulf in the prevalence of bad tastes and rebound? Ali Ellebedy, an immunologist at Washington University in St. Louis, told me he couldn’t imagine any direct link between vaccination and Paxlovid rebound or dysgeusia. And if anything, he said, immunological principles suggest that, compared with unvaccinated people, the vaccinated should have fewer cases of rebound, not more. Then again, “with COVID over the last two and a half years, we have been wrong—I have been wrong—so many times,” he said.

Providers are certainly anxious to know how many of their vaccinated patients experience Paxlovid rebound. But on a more basic level, they’re anxious to know how well the drug works in vaccinated people at all. “We really know nothing about the magnitude of its benefit or its risk in people who are vaccinated, let alone triple or quadruple vaccinated,” Walid Gellad, who directs the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, told me. Without that information, if a doctor has to decide whether to prescribe Paxlovid to a patient who’s eligible, “you make your best guess,” Gellad said.

Pfizer has hinted at some sunny results in vaccinated people, but no data have been made publicly available. Also, way back in December, the company said it had finished enrolling participants for a follow-up study of Paxlovid in people who are not at high risk of severe COVID. But then, a few months later, it changed the eligibility criteria to leave out anyone who had received a vaccine dose in the preceding 12 months.

Today, that follow-up trial is still listed as in the “recruiting” phase on ClinicalTrials.gov. Reshma Ramachandran said the changes are a “red flag” that Pfizer might have uncovered some preliminary results among vaccinated participants that weren’t so flattering. David Boulware, a clinical-trial expert at the University of Minnesota, told me that he thinks the rationale for Pfizer’s actions is “pretty obvious”: The company will have an easier time proving the drug works in people who are more likely to be hospitalized—that is, the unvaccinated (and those whose vaccinations are more than a year old). “From a pure researcher perspective, I can understand exactly why they did this. But from a public-health and just, like, being-a-physician perspective, it’s a terrible idea.” The Pfizer spokesperson told me that the company had limited enrollment to patients who had not received a vaccine dose for at least a year in order to “enrich the study population for individuals whose immunity may be waning and who may be at elevated risk of severe COVID-19, hospitalization or death.”

To make the best decisions possible regarding prescribing Paxlovid, doctors and patients would need to understand how common rebounds are, whether the drug causes them, and whether people are infectious during the rebound period. They’d also need to know whether the drug has any meaningful benefits for people who have gotten a primary vaccine dose or booster shot since May 2021. Boulware said he expects researchers in the United Kingdom to have data on Paxlovid’s efficacy in vaccinated people within the next couple of months. Gellad is also eager to know whether Paxlovid helps stave off long COVID, a hypothesis that would by definition take months or years to test. Ali Ellebedy is curious about whether taking Paxlovid dulls a patient’s immune response to the virus and therefore could leave them more vulnerable the next time they encounter it.

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

Until those questions are answered, the providers I spoke with are all erring on the side of prescribing Paxlovid. “You’re kind of stuck as a prescriber,” Gellad said. Doctors could wait and advise their vaccinated patients not to take the drug until they’re certain it’ll help, but vaccinated people are still getting sick, developing long COVID, going to the hospital, and dying. To draw a balance between caution and action, Ramachandran said that when she prescribes Paxlovid to her vaccinated patients, she also explains that the clinical trials weren’t conducted in people like them, and so exactly what they’ll get out of the drug is uncertain. “When we’re trying to look for options for COVID-19, especially for treatment, we just have so few options,” she said. For now, Paxlovid is the best bet.

Can Anyone Out-Plan a Pandemic?

2022-05-11T15:24:00-04:00

In this, the season of Bill Gates’s atonement, the billionaire is willing to acknowledge that things don’t always turn out as they should have, and that—at least in some cases—that’s on him. There was the high-profile divorce from his wife of 27 years, Melinda French Gates (“definitely a sad thing,” he said); allegations of an affair and inappropriate flirting at work (“false, recycled rumors,” a spokesperson insisted); and his association with the convicted sex offender Jeffrey Epstein (a “big mistake” on a whole list of them).

But Gates is not one to dwell on the painful past, particularly when that past conflicts with his arduously cultivated image as the world’s preeminent techno-savior. Bill Gates is a doer. And a fixer. And the thing he’s most focused on now is how he can help save the world from the next pandemic. After all, he’s seen for himself that no one man—not even a president, not even an innovator, not even a billionaire—was able to stave off this one.

I recently met with Gates, whose foundation has long preoccupied itself with global public-health initiatives, to talk about what he might do differently next time, and what we can learn from the hell of the past two years. His obsession with the subject is honorable, but I had to notice that his approach felt a little, well, predictable. Gates bets big on futuristic biotech—a library stocked with millions of antiviral drugs, for example, and machines that can test 150,000 samples a day for multiple pathogens. But the major building blocks for his plan are decades old: He wants better disease surveillance; more drugs to treat the infected; and enough shots to vaccinate as many people as possible, as quickly as possible. How should we prevent the next pandemic? By doing the things we try to do already—only better.

Much of the world’s response to the coronavirus—and America’s response in particular—has been, to put it lightly, a mess. It’s telling of our sorry situation that Gates’s grandest ambitions are simply to do the most basic things right—to have a real plan and stick to it. But while one big lesson of the pandemic has been how badly plans are needed, another has been how easily even the best ones fail.

I spoke with Gates at the Washington, D.C. Four Seasons hotel, in a windowless basement conference room at a table lined with empty chairs and unopened water bottles. Gates was on a multicity promotional tour for How to Prevent the Next Pandemic, a book that lays out in 215 pages his vision for avoiding future catastrophic global illness. A few notable points: Governments should encourage innovation, cut red tape, and agree to manufacture game-changing global-health tools. Everyone in the world should have access to good primary health care. One chapter focuses on organization; each country should appoint a pandemic czar, it says, while the whole world creates a full-time pandemic-prevention organization called “the GERM (Global Epidemic Response and Mobilization) team.” The next chapter focuses on improving disease surveillance, another on practicing the world’s response through simulated outbreaks, and so on.

The book is in fact Gates’s second about averting an existential global crisis in just as many years. His first world-saving manifesto, How to Avoid a Climate Disaster, came out in February 2021. Although saving all of humanity is indeed a grand mission, Gates’s choice to do so by way of a $19 hardcover is somewhat quaint, if not outright confusing. He is one of the world’s richest human beings. He takes private meetings with prime ministers and presidents, and pours money into projects that tackle—among other things—education, tobacco control, nutrition, maternal health, and a slate of diseases. (Disclosure: The Bill & Melinda Gates Foundation also has supported some Atlantic events and projects.) What good does a book do?

Gates sipped from a can of Diet Coke while he listened to this question. Then he failed to answer me at great length, instead going on an extended jag about the good his foundation and wealth have done. With How to Prevent the Next Pandemic, he said finally, “I thought I had an opportunity to be somewhat educational and frame in a fairly straightforward way what things would make it very, very different next time.” He told me that he hoped his writing would help readers understand complicated issues in a nonpartisan way. (A book, it’s worth noting, is also one way to attempt to shift public focus from questions about your failed marriage, or alleged impropriety at work, or friendship with a sexual predator.)

I asked Gates whether many parts of his pandemic-prevention scheme weren’t already embedded in preexisting plans. He didn’t deny it, but argued that new inventions and research would pave an easier path to success this time around. We have mRNA vaccines, he told me; we have Gavi, the Vaccine Alliance, which helps poor countries buy immunizations (and has received more than $4 billion from the Gates Foundation); and crucially, “we have a much better understanding of why people die.”

Gates is, in this way, an optimist. To believe that you need only a plan rests on an assumption that humans are rational creatures who have roughly the same values and priorities as you do, and—even more improbable—that humans are inclined to follow plans of any kind. After all, when Gates laid out a strategy for solving climate change last year, he was boldly going where world leaders had gone many, many times before without success. The United Nations has held no fewer than 26 annual climate-change conferences. The world committed to the Kyoto Protocol in 1997, but failed to meet its goals. The Paris Agreement is seven years old, and the UN itself says we’re falling short. But Gates told me that the plan he offered in How to Avoid a Climate Disaster has already done some good for the planet. “I feel like the book played a strong role in getting the dialogue onto the only way to square the circle, which is through innovation,” he said. In the meantime, Gates is pursuing a billionaire’s more traditional channels of persuasion: access to other people in power. “I have an ongoing conversation with Joe Manchin about climate-related things,” he told me. “You know, the tax credits that may or may not make it into some reconciliation bill.”

Like the world’s unmet climate goals, the graveyard of unfollowed pandemic plans is dispiriting. Gates’s new book cites a report published by the International Health Regulations Review Committee after the 2009 swine-flu outbreak, which “prophetically” concluded that the world was not ready for a pandemic—but its advice went unheeded. By March 2020, the Trump administration was lagging severely behind on many steps of a 2016 pandemic plan from the National Security Council and utterly flouting others. Before Joe Biden took office, he released yet another pandemic plan that included a promise to “ensure equity throughout the vaccination process” and make shots widely available for free; in reality, Black and Hispanic Americans didn’t receive vaccines as quickly as their white peers, and uninsured people might need to pay out of pocket for future doses.

Gates assured me that this time, the plans would be followed. “I don’t think either party is for pandemic death” in the U.S., he said, and global health is much cheaper than other world-saving projects. Gates writes in his book that the GERM team could run on a cool $1 billion a year, while the improvements the team would recommend to individual governments would cost a total of $15 billion to $20 billion a year over a decade, for the whole world. Compare that with the Green New Deal, which would probably cost Americans between $10 trillion and $93 trillion.

After so much death and suffering over the past two-plus years, Gates told me, “it would be so weird, so—you know—irrational, not to fund something.” The choice seemed so obvious, he said, that he’d been worried, while writing the book, that people would tell him, “Well, Bill, of course, we all know that. You didn’t need to write that down.” He figured that by the time the book came out, his plan, or something like it, would already be in motion.

Now he’s less confident, especially since Russia began its war on Ukraine. If fuel and fertilizer become harder to find, and inflation continues, and national budgets become too bloated with defense spending, and powerful people become distracted, then “that creates the risk, along with the polarization we’ve got, that maybe we won’t fund pandemics, which is stunning,” he said. “I’m mostly optimistic, but governments doing the right things is, you know—it’s a challenge. And the level of discussion about preparing for the next pandemic is less than I would have expected.”

But like any master planner, Gates has a contingency. The last chapter of How to Prevent the Next Pandemic, a book that is effectively a giant plan with lots of context, is called “Make—and fund—a plan for preventing pandemics.” A plan for making a plan: Now, who wouldn’t get on board with that?

Paxlovid Mouth Is Real—And Gross

2022-05-05T15:15:08-04:00

More than two years into this pandemic, we finally have an antiviral treatment that works pretty darn well. Paxlovid cuts a vulnerable adult’s chances of hospitalization or death from COVID by nearly 90 percent if taken in the first few days of an infection. For adults without risk-heightening factors, it reduces that likelihood by 70 percent. Also, it might make your mouth taste like absolute garbage the whole time you’re taking the pills.

In Pfizer’s clinical trials, about 5.6 percent of patients reported an “altered sense of taste,” called dysgeusia in the medical literature. A Pfizer spokesperson assured me that “most events were mild” and “very few patients discontinued study as a result”; the outer packaging of the drug doesn’t mention it at all, and the patient fact sheet breezes past it. But Paxlovid-takers told me it’s absolutely dysgeusting.

The bad taste may come on shortly after people take their first set of pills. (If prescribed Paxlovid, you’re supposed to take three pills, twice daily, for five days.) For a 36-year-old dog walker in Washington, D.C., named sangam 'alopeke (who styles their name without capital letters), the effect emerged within about an hour of the first dose. Lindsay Wright, a 40-year-old creative director in Winnipeg, Canada, said she noticed it after 90 minutes. Sheila Borkar, a 30-year-old transportation engineer who also lives in Washington, took a pill before bed and woke up to the taste.

“I imagine this is what grapefruit juice mixed with soap would taste like,” Anna Valdez, a nursing professor in Sonoma Valley, California, told me. (We communicated over Twitter direct messages because Valdez had lost her voice from COVID.) “It is horrible and does not go away.” Borkar was reminded of acid reflux. “This didn’t taste like food,” she said. “It didn’t quite taste poisonous, but it definitely tasted like something that should not be consumed.” Her friend Jeffrey Holliday, a 33-year-old business analyst, told me, “It tasted like I chewed a bunch of vitamins.”

“I heard that for some people, it’s a metallic taste, and I’m a little jealous,” Wright said. “I’m describing it as, like, bitter, burnt grapefruit, but mixed with—you know that taste when you try to swallow Tylenol and it doesn’t go down the first time? It’s a little bit of that failed-Tylenol-swallow mixed in.”

While dysgeusia is listed as a side effect of many drugs, including antibiotics, chemotherapeutics, and antihistamines, the specific experience varies. In many cases, patients report a bitter or metallic taste, Steven Munger, the director of the University of Florida’s Center for Smell and Taste, told me. That might be because human mouths are more primed to detect bitterness, in all its subtleties, than other flavors. According to Munger, humans have one kind of taste receptor for sweetness, one for umami, one for salt, two for sourness, and a whopping 25 for bitterness. That makes evolutionary sense, he said: Many toxic substances are bitter, so it’s more important that we taste them. “If the sweet receptor misses something, okay, well, maybe there’s more food coming along. That’s not going to be a life-or-death situation. But ingesting something that’s toxic could kill you.”

[Read: The paradox of sour food]

Munger told me that Paxlovid Mouth might result from chemesthesis, a chemical-sensing process that we often conflate with taste. (We sense both the chill of menthol and the heat of chiles through chemesthesis, not taste.) Or it could just be plain old taste, or a combination of the two.

If taste is the culprit, one bitter-taste receptor in particular might be to blame: TAS2R7. Danielle Reed, of the nonprofit Monell Chemical Senses Center, told me that the receptor has a “metallic, bitter vibe to it.” TAS2R7 isn’t activated very often in our daily lives, Reed said, because the compounds that bind to it are not in our foods, because—again—they taste awful. That might explain why those with Paxlovid Mouth have had trouble naming exactly what they’re going through, and why it feels so strange. “I’m a pretty adventurous eater normally. I’m usually the one that likes flavors other people don’t like. But this was over the line,” Borkar said.

TAS2R7 can be activated by metal salts, including magnesium sulfate, a.k.a. Epsom salt. You’re not supposed to eat it, but Reed told me if I tasted it and spat it out, I’d probably be fine. All I had at home was lavender-scented Dr. Teal’s Pure Epsom Salt Soaking Solution, but I tried it anyway. When I put a few crystals on the tip of my tongue, I had the sensation of having licked a lamppost. When I tried some farther back on my tongue, the flavor was extremely sour, with hints of dime. I suddenly understood what Wright meant when she said, “I think I might be ruined for grapefruit for the rest of my life.”

When I asked Pfizer about the funny taste, a spokesperson said, “Paxlovid is a combination of nirmatrelvir and ritonavir tablets … Both nirmatrelvir and ritonavir are bitter substances, which may contribute to the reports of taste-related side effects.” That clears things up! Of course, most tastes last for about as long as you’re eating something. The same was true for Epsom salt: It activated my TAS2R7 receptor, but then stopped activating it after I’d washed my mouth out with water. But Paxlovid Mouth works differently: “It is constant now,” Valdez told me. “I can taste food for the first bite or two, and then the bitterness takes over.” (Even pine nuts have been associated with a metallic taste that can last for weeks after eating them.)

Two possible mechanisms could explain that lingering, Reed said. Some molecules simply stick to our taste buds better than others, even when you try to wash them off by rinsing your mouth or brushing your teeth. (Many people experience this with high-intensity sweeteners, such as the ones in diet sodas.) Other molecules have a way of tickling our taste receptors even after they’re absorbed into the bloodstream; some medications, for example, can be excreted back into the mouth via saliva.

[Read: Families are going rogue with rapid tests]

The sticking-around-in-the-bloodstream theory makes particular sense given what Pfizer told me about the combination of drugs in Paxlovid: “Nirmatrelvir is a novel molecule designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.” So if nirmatrelvir is causing the dysgeusia, ritonavir could be working to extend the effect.

The Paxlovid Mouthers have been coping with their lasting flavor in different ways. “I’m, like, constantly with a lozenge or Tic Tacs or mints or like something in my mouth to try and mask it a little bit. But nothing really takes it away,” Wright said. 'alopeke has mostly been eating applesauce, which “doesn’t have a ton of flavor already, but is at least not actively disgusting to mix with the Paxlovid taste.”

Still, everyone I spoke with who had experienced Paxlovid Mouth said they’d take the drug again if they were reinfected and had another bout of COVID. “It’s a hell of a lot better than a ventilator,” Wright said. She’s immunocompromised, and has taken her fair share of medicines throughout her life. “It’s not my first encounter with a medication that leaves kind of a taste in your mouth,” she told me. “But I’ve never experienced anything this extreme. This is next-level.”

The Atlantic Daily: Republicans Could Just Call Trump a Loser

2022-04-27T19:00:00-04:00

Over the past several days, newly public reporting has revealed that Senate Minority Leader Mitch McConnell and House Minority Leader Kevin McCarthy harshly criticized Donald Trump after the January 6 attacks on the U.S. Capitol. “The Democrats are going to take care of the son of a bitch for us,” McConnell, then majority leader, told advisers. McCarthy was caught on tape saying that he would push Trump to resign.

As my colleague David Graham wrote last week, when McConnell and McCarthy shrug off concerns about January 6 now, “they are committing an act of moral and political cowardice.” Perhaps they feel like they can’t criticize Trump, because doing so has cost other Republican candidates and leaders (hello, Liz Cheney).

But as our staff writer Mark Leibovich argues, in the 2024 presidential primaries, “some nervy Republican challenger” just might come out on top by calling the former president a loser. Trump’s dominance is only part of the conventional political wisdom that our writers think is due for a shake-up.

Trump can be toppled. “If it was true in 2016 that other Republicans couldn’t touch Trump, it’s not necessarily so now, given the win-loss record he has since accumulated,” Mark writes.
Candidates with shady pasts could win—or lose—the Senate for the GOP. “In the Trump era, no one knows where, or whether, voters will draw a line on candidates who might have been unacceptable in the past,” our staff writer Russell Berman notes.
Democrats win when they get off the high road. After a colleague accused Michigan State Senator Mallory McMorrow of grooming children, she fought back. “McMorrow proved that rebuttal can be done effectively—and she succeeded because her rebuke rested on a personal narrative,” our contributing writer Molly Jong-Fast argues.

Further reading: America’s political dysfunction is turning school boards away from the business of schooling, my colleague Adam Harris writes.

The rest of the news in three sentences:

Russia stopped supplying gas to Poland and Bulgaria, which in turn distribute gas to Germany, Hungary, and Serbia.
A manufacturer recalled more than 120,000 pounds of ground beef over E. coli concerns.
Anthony Fauci said that the United States is “out of the pandemic phase” of COVID-19.

Latest dispatches: Non-fungible tokens are coming for New York’s nightclub scene—but money can’t buy cool, and never could, Xochitl Gonzalez argues in the latest Brooklyn, Everywhere. And in Up for Debate, Conor Friedersdorf asks readers: What types of speech should Twitter forbid, specifically?

Tonight’s Atlantic-approved activity: Do a puzzle. Hopefully you’ll finish before the world ends.

A break from the news: Kids make the best philosophers. (Want a single great story like this sent to your inbox each weekday? Sign up for One Story to Read Today.)

The Atlantic Daily: Three Possible Futures for a Musk-Owned Twitter

2022-04-25T19:30:00-04:00

Every weekday evening, our editors guide you through the biggest stories of the day, help you discover new ideas, and surprise you with moments of delight. Subscribe to get this delivered to your inbox.

The platform everyone loves to hate has a brand-new owner: Elon Musk is officially buying Twitter for approximately $44 billion.

Musk has a long and rocky history with Twitter—or tweeting, at least. Take his offer to buy the platform at $54.20 a share: It’s a not-so-subtle reference to when he claimed to be taking Tesla public at $420 a share on—where else—Twitter, and earned himself a consent decree from the Securities and Exchange Commission in the process. Musk has also used the platform to spread misinformation about COVID and feud with journalists.

The question now is, what will Musk do with Twitter when he owns it? Our writers offer some theories.

Musk might be in for a shock. Evelyn Douek, an internet researcher, argues that content moderation might be a problem that’s too hard to solve, even for the man who got rockets to land upright. “If Musk has a utopian vision of a libertarian internet, he should read about the history of content moderation,” Douek writes.
An Elon-owned Twitter could go one of three ways. In the worst version of the future, Charlie Warzel writes in his newsletter, Galaxy Brain, Musk could use the platform to push an extreme right-wing agenda. In the weirdest, he might attempt “lots of quick building, throwing shit at the wall, with very little consideration of the consequences.” But the most likely scenario, Charlie writes, is a return to the minimally moderated, harassment-heavy 2016 version of Twitter—including @RealDonaldTrump.

Further reading: “What Musk and others portray as a battle over ‘free speech’ is a proxy fight over who is entitled to attention,” Renée DiResta, of the Stanford Internet Observatory, wrote earlier this month.

The rest of the news in three sentences:

Donald Trump is being held in civil contempt in New York after failing to comply with a subpoena.
A wildfire in Nebraska killed a former fire chief; huge swaths of Arizona and New Mexico are burning too.
At a press conference, U.S. Defense Secretary Lloyd Austin said that the United States wanted to see the Russian military “weakened.”

Latest dispatches: Conor Friedersdorf recently asked his readers: If you had $1 billion to improve the world, how would you spend it? In his latest Up for Debate, he shared their answers. And in Work in Progress, Derek Thompson investigates whether America’s biggest cities are shrinking, or booming.

Tonight’s Atlantic-approved activity: Collaborate on a chore. Different-sex couples who do are more satisfied with their relationship than couples who divvy chores up, my colleague Joe Pinsker reports.

A break from the news: The world’s most exclusive bacon isn’t for sale.

The Atlantic Daily: The Case for Letting Ukraine Into NATO

2022-04-21T19:00:00-04:00

Russia, which has killed thousands of soldiers and civilians in its so-far largely futile invasion, reinvigorated its assault on Ukraine this week. Vladimir Putin claimed victory in the besieged city of Mariupol today, but a Ukrainian commander said his forces haven’t yet surrendered. Meanwhile, President Joe Biden announced a new weapons package for Ukraine and a system to allow Ukrainian refugees to enter the United States more quickly.

Aid alone, however, isn’t enough, writes Ivo Daalder, a former U.S. ambassador to NATO, in The Atlantic: “For Ukraine to be truly free and independent, it will have to be a member of the European Union and NATO.” Russia has claimed that NATO aggression forced it to invade Ukraine, but in fact, Daalder argues, “far from NATO being the proximate cause of war, NATO’s absence enabled Putin to act.”

Our writers lay out three other ways to understand the Russian president’s motives.

Putin is on an unholy crusade. The Russian president wants to form an Orthodox Christian empire and “believes that he is doing God’s will,” Tom Nichols writes in his newsletter, Peacefield. Despite the fact that Ukraine is a primarily Orthodox state, Russia’s highest Orthodox official has backed the war.
Putin has fallen into the dictator trap. Autocrats tend to make short-sighted, catastrophic errors that are less common in democratic systems, the political scientist Brian Klaas wrote last month. “Putin, like many despots, isn’t behaving fully rationally.”
He doesn’t want approval from the West. Russia has cranked up its efforts to punish independent media outlets for their alleged Western ties—but that’s only pushed Putin’s critics closer to Europe and the U.S., Maria Repnikova, a communications professor, writes.

(Jan Buchczik)

The rest of the news in three sentences:

The U.S. Capitol was briefly evacuated last night as an Army team prepared to parachute into a Washington Nationals pregame celebration.
After announcing plans to buy Twitter this month, Elon Musk told the Securities and Exchange Commission that he has enough funding to do so.
Queen Elizabeth II, the longest-ruling British monarch in history, turned 96 today.

Latest dispatches: Donald Trump’s endorsements might be the GOP’s kryptonite in the midterms, Molly Jong-Fast suggests in Wait, What? And in Galaxy Brain, Charlie Warzel describes why mid-flight unmasking videos are so uncanny.

One question, answered: How much protection do immunocompromised people really get from COVID-19 shots? Benjamin Mazer, a clinical pathologist, reports:

Regarding the most dangerous outcomes from disease, recent research from the CDC indicates that—shot for shot—the immunocompromised achieve most of the same benefits as healthy people. One study, published in March, looked at the pandemic’s Delta wave and found that three doses of an mRNA vaccine gave immunocompromised people 87 percent protection against hospitalization, compared with 97 percent for others. Another CDC report, also out last month, suggested that on the very worst outcomes—the need for a breathing tube, or death—mRNA vaccines were 74 percent effective for immunocompromised patients (including many who hadn’t gotten all their shots), and 92 percent effective for the immunocompetent. A 10-to-20-percentage-point gap in safety from the most dire outcomes is consequential, especially for those who are most susceptible to the disease. Still, these results should reassure us that the immunocompromised are not fighting this battle unarmed.

Read the full story.

Tonight’s Atlantic-approved activity: Walk for an hour. Read for an hour. Or try another of these 10 practical strategies to improve your happiness.

A break from the news: The seventh planet from the sun could use some attention.

What Masks Off on Public Transit Means for the Pandemic

2022-04-20T16:51:11-04:00

Updated at 6:50 p.m. ET on April 20, 2022

If you commuted to work today on a bus, train, or metro system, you probably saw more mouths and noses than usual. On Monday, a Trump-appointed federal judge struck down a CDC rule that mandated masks on all U.S. transportation networks, including in airports and on planes. Airline passengers who were mid-flight when the news broke cheered and ripped their masks off, discarding them in trash bags that unmasked flight attendants helpfully brought up and down the aisle.

Over the past several months, vaccine requirements in restaurants, mask mandates in schools and retail spaces, and testing requirements for workers have all been reversed. But the end of airplane masking in particular has inspired a disproportionate reaction—of both extreme relief and utter outrage. One pilot reportedly called the end of the mandate “the most important announcement I’ve ever made.” An ER doctor wondered how “people who claim to love kids are totally cool” with babies dying from COVID. Why, exactly, is this rollback so different from all other rollbacks?

In some ways, the masking rules on transportation should matter less for public health than other masking mandates, not more. Most people who don’t work in transportation probably spend relatively little time in train stations, buses, and Jetways, as compared with workplaces, where mask requirements are already scarce. Joseph Allen, who directs Harvard’s Healthy Buildings program, told me that, in general, ventilation is also better on trains and airplanes than it is in restaurants, offices, and homes. (That’s true only as long as the HVAC system is actually turned on, which it tends not to be while a plane is on the tarmac.) On buses, ventilation depends on whether the driver has the vehicle in air-recirculation mode. “There’s been too much attention on the risk in airplanes for a long time,” Allen said. “Airplanes are not where super-spreading is happening.”

In the broadest sense, removing the transportation-network mandate is not likely to have an enormous, near-term effect on the trajectory of the pandemic. Even if mask compliance on subways and buses suddenly went down to, say, 10 percent in a major American city, any increase in cases or hospitalizations “would probably be small—small to the level of not being detectable by our current surveillance systems,” David Dowdy, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, told me.

Whether or not masking on buses keeps community spread in check, it has other benefits. “For me, the mask mandate is not simply a tool to control transmission, but rather one that makes our essential spaces safer and accessible for everyone,” Anne Sosin, a public-health researcher at Dartmouth, told me. People who are at risk because they are very elderly, or who get a bit less benefit from the vaccines because they’re immunocompromised, or who have small children, can generally avoid bars and concert venues if they want to. Buses and metros are much harder to steer clear of. Black and Hispanic Americans, who have gotten sick and died at higher rates than their white peers throughout the pandemic, are more likely to use public transportation—and more likely to support mask mandates there.

All the experts I spoke with said the change in policy itself was less significant than the manner in which that change was carried out. Other pandemic restrictions have generally been allowed to expire or repealed by the same authorities that instituted them. The public-transportation mask mandate was implemented by the CDC and repealed by a federal judge in Tampa, Florida. The Department of Justice appealed the ruling today, but if it loses—especially if the case makes it to the Supreme Court—then the federal government’s ability to enact restrictions could be limited far beyond this summer. “If something unpredictable happens next, where we need CDC to put in mandates, that authority’s in question,” Allen said. That could be especially dangerous if the country is dealing with a new variant or a new pathogen that spreads to new areas via interstate travel.

The rollback of the transportation-network mandate also feels different because it was among the very last, broad restrictions that were still in place. Throughout the pandemic, public-health experts have touted a Swiss-cheese approach to protection: No single approach is perfect, whether it be masking, vaccination, or social distancing; but layering them all together helps cover up the holes. Each restriction that gets pulled back is another slice of cheese gone, another way the population becomes more vulnerable. Now, with no more masking on airplanes, trains, and buses, we’re almost dairy-free.

Until this week, transportation hubs were the only place left where many Americans were required to be masked. A handful of regional transit agencies, including in New York City and Portland, Oregon, are still demanding that their riders cover up. But in communities across the country, Americans face few, if any, pandemic restrictions. A vaccination requirement for federal workers still stands. But other than that, Sosin said, “this is the last domino to fall.”

The Atlantic Daily: Welcome to the Trump Cinematic Universe

2022-04-18T19:30:00-04:00

Hi! I’m Rachel, and I’ll be your Daily host for (most of) the next two weeks. I write and edit for our Science, Technology, and Health section, and edit the column “How to Build a Life.” I’ve been on the pandemic beat for the past two years, but also enjoy exploring surprising facts about animals, language, and food. Say hello at rgutman@theatlantic.com.

Sixty-eight percent of Republicans do not believe that the 2020 election was free and fair, but few can explain exactly why. “I can’t really put my finger on it, but something just doesn’t feel right,” one Donald Trump voter told Sarah Longwell. “It didn’t smell right,” another said.

The leading conspiracy theories about the election are exactly that—conspiracy theories. But for people who are immersed in what my colleague David Frum calls the Trump Cinematic Universe, they make perfect sense.

Boycotting presidential debates is only logical for Trumpists. “What the RNC is saying with its vote is, Unless we know in advance that a debate moderator believes in the same version of reality as we do, we will not participate at all,” David writes.
The GOP says it’s the party of parents, but that’s a myth. If Republicans cared about children, even just white children, “then they would not be ignoring or downplaying or defending or bolstering the principal racial threat”—white-supremacist ideology—“facing white youth today,” Ibram X. Kendi argues in a new essay.
Republicans say sex education is grooming. In fact, it’s the opposite. Teaching kids about sex, even in elementary school, can help keep them safe from abusers, my colleague Olga Khazan reports.

The rest of the news in three sentences:

Ukrainian President Volodymyr Zelensky announced that Russia has launched a full-scale invasion of the Donbas region.
Shanghai reported its first deaths from China’s current COVID-19 wave yesterday, even as the city remains under a punishingly strict lockdown.
Peres Jepchirchir won the women’s division in the 2022 Boston Marathon; Evans Chebet won the men’s.

Latest dispatches: Watching Tony Hawk’s slow-motion self-destruction in a new HBO documentary is painful—and inspiring, Jordan Calhoun writes in Humans Being. In Up for Debate, Conor Friedersdorf compiles 12 reader views on where America is going wrong. And The Good Word’s Caleb Madison explains why we’re calling everything a “hellscape.”

Tonight’s Atlantic-approved activity: Watch the final season premiere of AMC’s Better Call Saul, which airs tonight. The show is “an energetic embrace of TV’s promise,” our critic Spencer Kornhaber writes.

A break from the news: Can women buy empowerment through NFTs?

Seriously, Why Not Get a Fourth Shot?

2022-03-31T13:08:15-04:00

The FDA and CDC have cleared the way for Americans older than 50 to get a second booster shot—but they don’t quite suggest that everyone in that age group should do so. Like masking and many other pandemic-control measures, a fourth dose (or third, for the J&Jers in the back) is now a matter of personal judgment, even as another wave of COVID cases seems poised to break. That leaves millions of Americans and their doctors to perform their own risk-benefit analysis.

[Read: Another COVID wave is looming]

Or perhaps it’s just a risk analysis. The upsides of a fourth shot are indeed uncertain: The best we can say right now is that its protective effects are probably modest and temporary (with greater benefits for older people). But a modest, temporary boost is still better than nothing—so why not go ahead and get one, just in case? What, if any, risks would that actually entail?

The potential downsides of an extra boost have so far been described in rather vague, confusing terms. A New York Times article published Tuesday, “Should You Get Another Booster?,” warned that repeated boosting “offers diminishing results.” (Again: Sounds better than nothing!) The article also said that getting too many original-vaccine doses could make your body less responsive to an improved formula, and that it might be worse for your longer-term immunity than waiting. Céline Gounder, a former member of President Joe Biden’s COVID transition team, pointed out on Twitter yesterday that repeated boosting could pose certain “psychological risks,” including “vaccine fatigue and skepticism”—but these are more relevant to public-health officials than individual Americans seeking shots.

[Read: America’s flu-shot problem is also its next COVID-shot problem]

For those seeking clarity, here’s what we know for sure. A second round of boosters will come with two cons: They’ll cause side effects such as fever and body aches, probably at about the same level as side effects from a first booster, and they’ll be expensive for uninsured Americans, thanks to the government’s rejecting billions in COVID spending this month. Beyond that, the risks are only theoretical. “There’s no good data in humans yet for SARS-CoV-2 that boosting too frequently is going to cause damage to the system,” John Wherry, an immunologist at the University of Pennsylvania, told me.

A couple of potential drawbacks can be ruled out right away. According to one idea, too many boosters could lead to something called “immune exhaustion,” in which a person’s relevant T cells, after trying to fight off an intruder for years on end, begin to wear down. They “become literally exhausted; they are no longer functional,” Akiko Iwasaki, an immunologist at Yale, told me. This can affect people with chronic infections such as HIV, or even tumors. But vaccines involve limited, not chronic, exposure to the coronavirus’s spike protein, and there’s no evidence that boosters spaced four months apart would exhaust anyone’s immune system, Iwasaki said—although “if you’re giving it every week, that’s a different story.”

Another virtually moot risk is one floated in the Times: that repeated exposure to a vaccine designed around the original SARS-CoV-2 virus could train a person’s immune system (through a process called imprinting) so narrowly that it won’t recognize new variants. Such an effect is theoretically possible, but not supported by evidence and not worth worrying about at this point, Marion Pepper, an immunologist at the University of Washington, told me.

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Getting an unnecessary shot could, in theory, put you at an immunological disadvantage in another way, by interfering with your immune response to a previous COVID shot or infection. One recent study, set to be published in Cell in April, found that people who received three shots saw their antibody levels rise by a factor of up to 100. But among people who had also gotten COVID—that is, those for whom the booster represented a fourth exposure, rather than a third—the increase was much smaller. That’s an example of the “diminishing returns” problem, which wouldn’t really matter if you cared only about your antibody levels. (A lot plus a little is still more than a lot.) But Wherry, who led the Cell study, told me that the smaller increase might have knock-on effects in other parts of the immune system, and end up limiting the B cells that will react to the virus the next time you encounter it.

Here’s how that works: When you get a booster shot or become sick with COVID after being vaccinated, some of your B cells will enter a structure in the lymphoid tissue called a germinal center, a sort of training camp that produces other, more diverse B cells that can respond to all sorts of invaders. If you leave those training camps alone for long enough, they’ll also produce long-lived plasma cells, which hang out in your bone marrow and manufacture antibodies all the time. But an extra booster shot could interrupt that process, Pepper told me, leaving you without the full, long-term benefit of those plasma cells.

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All of this means that the longer you wait between shots, the more durable the protection you get. In animals, Wherry said, the benefits of waiting start to plateau after about six months, but in humans, the optimal delay isn’t known. Pepper doesn’t think this drawback would come into play for those who got their third shot at least four months ago, as the CDC recommends. “I don’t think getting a booster is going to disrupt anything,” she said. She also recommended that people wait at least four months after their most recent infection for the same reason. But if you get two boosters within, say, a month, Pepper suspects that you’d end up with less protection in the long run than if you’d gotten only one.

Wherry is more inclined to see a possible trade-off, albeit a small and uncertain one. Even if it’s been at least four months since your last booster or infection, choosing whether to get a shot could mean balancing some short-term protection against infection (largely conferred by antibodies) with some long-term protection against severe disease and death (the domain of B and T cells), he told me. Wherry said that older people should give more weight to the former, because as we age, our B- and T-cell responses tend to slow down. Still, everyone should make that decision with their doctor, taking their own health into account. “A 67-year-old marathon runner with no comorbidities, no health issues, is going to be a very different scenario than a 72-year-old lymphoma patient on immune-modifying drugs.”

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What about the risk of getting a booster now, and therefore missing out on the full effects of some new and better COVID vaccine in the next four months? For now, this doesn’t seem like a significant concern. New vaccines that have been tailored to the altered spike proteins of the Omicron variant so far don’t appear to work any better than the original formulas. And any new vaccine based on something other than the spike protein won’t be affected by an encounter with our existing shots, Wherry said. Yale’s Iwasaki, who works on mucosal vaccines, said that many designs might even be made stronger by a recent vaccination or infection. If we do get a truly unfamiliar variant and need a truly new vaccine to combat it, producing and distributing one would probably take more than four months anyway.