Tag: high risk

‘An absolute scorcher’: Sweltering heat, wildfire risk loom for July Fourth weekend

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Blazing heat and increased wildfire risk will grip Southern California through the Fourth of July weekend and into early next week, with temperatures peaking above 115 degrees in desert areas Friday and forecasters issuing heat warnings and advisories throughout the region.

Extreme temperatures and gusty winds will also combine with dry conditions to create a high risk of new wildfires throughout the state as the Thompson fire continues to burn across more than 3,500 acres north of Sacramento.

“Tomorrow is going to be an absolute scorcher,” Joe Sirard, a meteorologist at the National Weather Service office in Oxnard, said Thursday morning. “It’s not your typical heat wave. This is a dangerous heat wave, this is a high-end heat wave. Very dangerous.”

Heat warnings were in place Thursday for much of L.A. County’s valleys and deserts as well as the Santa Monica Mountains.

Construction workers on a sidewalk improvement site toil as temperatures rose into the triple digits in Palmdale over the holiday.

(Brian van der Brug / Los Angeles Times)

The predicted highs for July 4 hovered around 106 degrees in the valleys, 103 in the lower mountains and 111 in desert areas, according to the National Weather Service. On Friday, temperatures are expected to soar as high as 110 to 112 degrees in the county’s valleys and mountains, and between 112 and 118 in the desert. The only parts of the county that aren’t experiencing extreme heat conditions, Sirard said, are coastal communities.

Officials advised Southern California residents to take precautions against exposure to high temperatures, which can elevate the risk of heatstroke and heat exhaustion. The National Weather Service called on people to stay in air-conditioned spaces during the day and early evening, stay hydrated, check on neighbors and the elderly and avoid strenuous outdoor activities.

“It’s just too hot,” Sirard said. “Just use common sense. It’s a dangerous heat wave and that’s why we have the heat warnings.”

Jacque McDonald, 39, drove with her husband and their two young children from their home in Tarzana to Hermosa Beach on Thursday morning to beat the high heat in the San Fernando Valley.

“We came here just because we know it’s going to be hot. I’m not about it,” McDonald said as crowds of people in bathing suits and sunglasses strolled by on the Strand and gray clouds helped keep the temperature down. “We have a pool at our complex, but we figured it would be packed. So we planned to come down here to the beach.”

Annie Seawright celebrates while being carried by people after winning the Hermosa Beach Ironman competition on July 4.

(Michael Blackshire / Los Angeles Times)

Just before noon, dozens of visitors shuffled down the dirt path at Eaton Canyon Natural Area, a popular L.A. County park in Altadena with a stream and a waterfall.

At the trail’s first water crossing, Mercedes Monje, 29, of Los Angeles sat along the bank with her partner and 2-year-old son splashing in the water while the rest of her family sat nearby.
Monje said her family usually hits a beach or river on the Fourth of July.

They originally planned Thursday to go to the East Fork of the San Gabriel River. But when they arrived about 8 a.m., they were told by authorities that it was full.

“We’re a little bit disappointed that we couldn’t be where we actually had planned to go, but we’re trying to make the best out of it,” Monje said.

Meanwhile, the risk of wildfires is high in inland areas, as is the chance that even small fires could quickly become larger conflagrations, given the extreme conditions.

“We’re expecting high heat today, which increases the chances for fire growth,” said David Acuna, a Cal Fire battalion chief. Fire departments across California urged people to resist the temptation to celebrate the Fourth of July by shooting off fireworks that could spark new blazes.

In Butte County, the Thompson fire remained just 7% contained as of Thursday morning, Acuna said, though it had remained steady at 3,568 acres overnight. He said 1,962 personnel, 20 helicopters, 214 engines, 46 dozers, 43 water tenders and 37 crews were fighting the fire. At its peak, about 12,000 structures were evacuated, affecting about 28,000 people.

“The firefighters on the line will continue to remain hydrated and ready in the event the fire acreage increases,” Acuna said, adding that though some have been downgraded, “a number of fire evacuations and warnings” remained in place near the blaze Thursday.

In Simi Valley, the Sharp fire was holding at 133 acres, and the containment was updated from 15% to 60% Thursday morning, according to Ventura County Fire Department spokesman Andy VanSciver.

Airn Barnes enjoys a cool fountain at Courson Park Pool as temperatures rose into the triple digits in Palmdale.

(Brian van der Brug / Los Angeles Times)

No structures have been damaged by the fire, which at one point prompted an evacuation order for 60 nearby homes and an evacuation warning for an additional 340. The orders and warnings were lifted Wednesday evening, VanSciver said.

“The containment lines have been holding and they’re being reinforced,” he said, adding that he didn’t anticipate wind conditions to cause the blaze to spread. “We have enough resources on hand to handle it.”

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Connor Sheets, Jaclyn Cosgrove

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July 4, 2024
Sick Season Will Be Worse From Now On

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Last fall, when RSV and flu came roaring back from a prolonged and erratic hiatus, and COVID was still killing thousands of Americans each week, many of the United States’ leading infectious-disease experts offered the nation a glimmer of hope. The overwhelm, they predicted, was probably temporary—viruses making up ground they’d lost during the worst of the pandemic. Next year would be better.

And so far, this year has been better. Some of the most prominent and best-tracked viruses, at least, are behaving less aberrantly than they did the previous autumn. Although neither RSV nor flu is shaping up to be particularly mild this year, says Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security, both appear to be behaving more within their normal bounds.

But infections are still nowhere near back to their pre-pandemic norm. They never will be again. Adding another disease—COVID—to winter’s repertoire has meant exactly that: adding another disease, and a pretty horrific one at that, to winter’s repertoire. “The probability that someone gets sick over the course of the winter is now increased,” Rivers told me, “because there is yet another germ to encounter.” The math is simple, even mind-numbingly obvious—a pathogenic n+1 that epidemiologists have seen coming since the pandemic’s earliest days. Now we’re living that reality, and its consequences. “What I’ve told family or friends is, ‘Odds are, people are going to get sick this year,’” Saskia Popescu, an epidemiologist at the University of Maryland School of Medicine, told me.

Even before the pandemic, winter was a dreaded slog—“the most challenging time for a hospital” in any given year, Popescu said. In typical years, flu hospitalizes an estimated 140,000 to 710,000 people in the United States alone; some years, RSV can add on some 200,000 more. “Our baseline has never been great,” Yvonne Maldonado, a pediatrician at Stanford, told me. “Tens of thousands of people die every year.” In “light” seasons, too, the pileup exacts a tax: In addition to weathering the influx of patients, health-care workers themselves fall sick, straining capacity as demand for care rises. And this time of year, on top of RSV, flu, and COVID, we also have to contend with a maelstrom of other airway viruses—among them, rhinoviruses, parainfluenza viruses, human metapneumovirus, and common-cold coronaviruses. (A small handful of bacteria can cause nasty respiratory illnesses too.) Illnesses not severe enough to land someone in the hospital could still leave them stuck at home for days or weeks on end, recovering or caring for sick kids—or shuffling back to work, still sick and probably contagious, because they can’t afford to take time off.

To toss any additional respiratory virus into that mess is burdensome; for that virus to be SARS-CoV-2 ups the ante all the more. “This is a more serious pathogen that is also more infectious,” Ajay Sethi, an epidemiologist at the University of Wisconsin at Madison, told me. This year, COVID-19 has so far killed some 80,000 Americans—a lighter toll than in the three years prior, but one that still dwarfs that of the worst flu seasons in the past decade. Globally, the only infectious killer that rivals it in annual-death count is tuberculosis. And last year, a CDC survey found that more than 3 percent of American adults were suffering from long COVID—millions of people in the United States alone.

Read: Is COVID a common cold yet?

With only a few years of data to go on, and COVID-data tracking now spotty at best, it’s hard to quantify just how much worse winters might be from now on. But experts told me they’re keeping an eye on some potentially concerning trends. We’re still rather early in the typical sickness season, but influenza-like illnesses, a catchall tracked by the CDC, have already been on an upward push for weeks. Rivers also pointed to CDC data that track trends in deaths caused by pneumonia, flu, and COVID-19. Even when SARS-CoV-2 has been at its most muted, Rivers said, more people have been dying—especially during the cooler months—than they were at the pre-pandemic baseline. The math of exposure is, again, simple: The more pathogens you encounter, the more likely you are to get sick.

A larger roster of microbes might also extend the portion of the year when people can expect to fall ill, Rivers told me. Before the pandemic, RSV and flu would usually start to bump up sometime in the fall, before peaking in the winter; if the past few years are any indication, COVID could now surge in the summer, shading into RSV’s autumn rise, before adding to flu’s winter burden, potentially dragging the misery out into spring. “Based on what I know right now, I am considering the season to be longer,” Rivers said.

With COVID still quite new, the exact specifics of respiratory-virus season will probably continue to change for a good while yet. The population, after all, is still racking up initial encounters with this new coronavirus, and with regularly administered vaccines. Bill Hanage, an epidemiologist at Harvard’s T. H. Chan School of Public Health, told me he suspects that, barring further gargantuan leaps in viral evolution, the disease will continue to slowly mellow out in severity as our collective defenses build; the virus may also pose less of a transmission risk as the period during which people are infectious contracts. But even if the dangers of COVID-19 are lilting toward an asymptote, experts still can’t say for sure where that asymptote might be relative to other diseases such as the flu—or how long it might take for the population to get there. And no matter how much this disease softens, it seems extraordinarily unlikely to ever disappear. For the foreseeable future, “pretty much all years going forward are going to be worse than what we’ve been used to before,” Hanage told me.

Read: The next stage of COVID is starting now

In one sense, this was always where we were going to end up. SARS-CoV-2 spread too quickly and too far to be quashed; it’s now here to stay. If the arithmetic of more pathogens is straightforward, our reaction to that addition could have been too: More disease risk means ratcheting up concern and response. But although a core contingent of Americans might still be more cautious than they were before the pandemic’s start—masking in public, testing before gathering, minding indoor air quality, avoiding others whenever they’re feeling sick—much of the country has readily returned to the pre-COVID mindset.

When I asked Hanage what precautions worthy of a respiratory disease with a death count roughly twice that of flu’s would look like, he rattled off a familiar list: better access to and uptake of vaccines and antivirals, with the vulnerable prioritized; improved surveillance systems to offer people at high risk a better sense of local-transmission trends; improved access to tests and paid sick leave. Without those changes, excess disease and death will continue, and “we’re saying we’re going to absorb that into our daily lives,” he said.

And that is what is happening. This year, for the first time, millions of Americans have access to three lifesaving respiratory-virus vaccines, against flu, COVID, and RSV. Uptake for all three remains sleepy and halting; even the flu shot, the most established, is not performing above its pre-pandemic baseline. “We get used to people getting sick every year,” Maldonado told me. “We get used to things we could probably fix.” The years since COVID arrived set a horrific precedent of death and disease; after that, this season of n+1 sickness might feel like a reprieve. But compare it with a pre-COVID world, and it looks objectively worse. We’re heading toward a new baseline, but it will still have quite a bit in common with the old one: We’re likely to accept it, and all of its horrors, as a matter of course.

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Katherine J. Wu

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November 30, 2023
America May Be Missing Out on a Better COVID Treatment

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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 metabolism 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.

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Rachel Gutman-Wei

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October 25, 2023
A Simple Marketing Technique Could Make America Healthier

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This article was originally published in Knowable Magazine.

Death from colorectal cancer can be prevented by regular screenings. Controlling high blood pressure could prolong the lives of the nearly 500,000 Americans who die from this disease each year. Vaccinations help prevent tetanus, which could otherwise be lethal.

Clearly, preventive medicine can make a big difference to health.

And yet most people don’t get the preventive care that could save their lives. Indeed, as of 2015, only 8 percent of U.S. adults 35 and older had received all immunizations, cancer screenings, and other high-priority services recommended for them.

Researchers seeking to change that are borrowing a page from Facebook, Google, and other tech companies. By rapidly comparing small differences in how they communicate with patients—a process known as A/B testing—health-care workers can quickly learn what works and what doesn’t. The approach has already delivered several actionable improvements, though not everyone is convinced of its value.

Tech-oriented companies use A/B testing to make decisions about marketing slogans, web-page colors, and lots of other options. The key is randomization, meaning that people are randomly assigned to see different versions of whatever is being tested. Does a bigger “Subscribe” button on a website generate more clicks than a smaller one? Does one headline over a story capture more readers than another?

Read: There’s no such thing as a casual interaction with your doctor anymore

Leora Horwitz, an internist and a health-services researcher at NYU Langone Health, and her colleagues adopted this technique—which they call rapid randomized controlled trials—to learn how to improve the delivery of health-care services. Randomized controlled trials, or RCTs, are widely used in medicine, typically to test new drugs or other disease treatments. For example, patients may be randomly assigned to receive either a new drug or the current standard treatment, then followed for months or years to assess whether the new drug works better. But those trials are slow and expensive, in part because researchers have to recruit people willing to be in a medical experiment.

Rapid RCTs, by contrast, are not used to study new treatments, so nobody has to be recruited to participate. Rather, Horwitz’s goal is to improve health-care delivery through quick trials in which one can repeatedly test and fine-tune changes to health-care delivery based on what researchers learn from each test.

“We are randomizing what we’re doing so that we can quickly and accurately assess whether what we are doing is working,” says Horwitz, who wrote about the approach in the 2023 Annual Review of Public Health.

For example, Horwitz and her colleagues wanted to figure out how to get patients to book appointments to address care gaps—preventive services that are overdue. Because of the huge number of patients, physicians’ offices can’t contact everyone by telephone or through the online portal that NYU Langone uses to communicate with patients. So the health system needed to understand what type of reminders were most effective.

In the A/B test, patients with care gaps were divided into two sets: those who had signed up for an online-portal account and those who had not. Patients in each set were then sorted into different groups based on their health-care history. Patients who, based on past behavior, were unlikely to initiate appointments on their own were put in higher-risk groups; those who had eventually booked their own appointments in the past were assigned to lower-risk groups.

In one part of the test, several thousand patients who had no portal account were randomized so that some received a telephone-call reminder and others did not. Patients who received a phone call booked appointments to address 6.2 percent of the care gaps, compared with just 0.5 percent among those who were not called.

In another part of the test, some patients with portal accounts received a reminder message through that channel, while others did not. Of those who received the message, 13 percent scheduled the needed services, compared with 1.1 percent of those who were not contacted.

Importantly, the experiments revealed that a phone-call reminder was the most effective way to reach the subgroups of patients who were high-risk and the least likely to get their preventive services without a nudge. Shortly after the test results were known, NYU Langone prioritized all of its highest-risk patients to receive telephone reminders and greatly expanded its capacity for sending messages through the patient portal.

“When we learn something, we apply that to all of our messaging quickly,” Horwitz says. That immediately extends what they’ve learned to tens of thousands of people. “That’s gratifying.”

Read: Do you really want to read what your doctor writes about you?

NYU Langone’s A/B testing is why many of the medical center’s female patients are now receiving short messages to remind them to schedule their mammograms. The researchers used rapid RCTs to test the wording on reminders sent through the online portal: Would shorter messages get better results? Indeed, patients who received a 78-word reminder scheduled nearly twice as many mammograms as those who received the old 155-word message.

In another investigation, to find out how to boost vaccination rates among very young children, Horwitz and her team turned to rapid randomized tests that compared one-text and two-text reminders to parents against no text reminder at all. Only the two-text reminder—one sent at 6 p.m., the other sent at noon two days later—made a difference, tripling the number of appointments scheduled. Most appointments were made after the second text, suggesting that this booster reminder was what triggered the parents to act.

Though it’s still new to the health-care sector, the idea of rapid RCTs is catching on. One research team—an economist, a physician, and a public-policy expert, none of whom was affiliated with Horwitz’s group—used the technique to learn how to increase the use of preventive-care services by Black men, the U.S. demographic group with the lowest life expectancy.

They recruited more than 1,300 Black men from Oakland, California–area barbershops and flea markets, asked them to fill out a health questionnaire, and gave them a coupon for a free health screening. A pop-up clinic, staffed with 14 Black and non-Black male doctors, was set up to provide the screenings, and the participating men were randomly assigned to a Black or a non-Black doctor. The result: Black men assigned to Black physicians were more likely to get diabetes screenings, flu vaccinations, and other preventive services than those assigned to non-Black doctors.

Some experts doubt that rapid A/B testing will ever become commonplace in health care. Darren DeWalt, a physician who directs the Institute for Healthcare Quality Improvement at the University of North Carolina, likes the concept, but he thinks most health-care organizations will avoid it for ethical reasons, possibly because people tend to disapprove of randomization, even in the context of something as innocuous as appointment reminders. “People in this country don’t like the idea that they are randomly allocated to something, even something as simple as that,” DeWalt says. “There’s a lot of suspicion around researchers in health care.”

Others criticize A/B testing as tinkering at the margins. Pierre Barker, the chief scientific officer for the nonprofit Institute for Healthcare Improvement in Boston, believes that significant improvements in health-care delivery require an in-depth analysis of the problem to be solved, which may require many changes to the system. By contrast, rapid randomized controlled trials focus on a single, discrete change—say, the words used in a telephone script—rather than a broader effort to understand why patients don’t get preventive services and what can be done to change that.

“The attractiveness is how fast it can move, more than the size of the impact,” he says. “I remain to be convinced that you can get more than a small incremental change” from rapid randomized controlled trials.

It is true that the majority of NYU Langone’s care gaps were not resolved by the new reminders, says Horwitz, but the tests did provide information that led to hundreds of potentially lifesaving services being performed. That is what convinces her that the health-care industry should embrace rapid randomized trials.

“If you were working for a web company or an airline or any other industry, you would randomize as a matter of course—this is the standard practice,” she says. “But it is still very foreign in health care, and it shouldn’t be.”

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Lola Butcher

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August 19, 2023
Trying to Stop Long COVID Before It Even Starts

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Three years into the global fight against SARS-CoV-2, the arsenal to combat long COVID remains depressingly bare. Being vaccinated seems to reduce people’s chances of developing the condition, but the only surefire option for avoiding long COVID is to avoid catching the coronavirus at all—a proposition that feels ever more improbable. For anyone who is newly infected, “we don’t have any interventions that are known to work,” says Akiko Iwasaki, an immunologist and long-COVID researcher at Yale.

Some researchers are hopeful that the forecast might shift soon. A pair of recent preprint studies, both now under review for publication in scientific journals, hint that two long-COVID-preventing pills might already be on our pharmacy shelves: the antiviral Paxlovid and metformin, an affordable drug commonly used for treating type 2 diabetes. When taken early in infection, each seems to at least modestly trim the chance of developing long COVID—by 42 percent, in the case of metformin. Neither set of results is a slam dunk. The Paxlovid findings did not come out of a clinical trial, and were focused on patients at high risk of developing severe, acute COVID; the metformin data did come out of a clinical trial, but the study was small. When I called more than half a dozen infectious-disease experts to discuss them, all used hopeful, but guarded, language: The results are “promising,” “intriguing”; they “warrant further investigation.”

At this point, though, any advance at all feels momentous. Long COVID remains the pandemic’s biggest unknown: Researchers still can’t even agree on its prevalence or the features that define it. What is clear is that millions of people in the United States alone, and countless more worldwide, have experienced some form of it, and more are expected to join them. “We’ve already seen early data, and we’ll continue to see data, that that will emphasize the impact that long COVID has on our society, on quality of life, on productivity, on our health system and medical expenditures,” says Susanna Naggie, an infectious-disease physician and COVID-drug researcher at Duke University. “This needs to be a high priority,” she told me. Researchers have to trim long COVID incidence as much as possible, as soon as possible, with whatever safe, effective options they can.

By now, news of the inertia around preventive long-COVID therapies may not come as much of a shock. Interventions that stop disease from developing are, on the whole, a neglected group; big, blinded, placebo-controlled clinical trials—the industry gold standard—usually look to investigate potential treatments, rather than drugs that might keep future illness at bay. It’s a bias that makes research easier and faster; it’s a core part of the American medical culture’s reactive approach to health.

Read: Long COVID has forced a reckoning for one of medicine’s most neglected diseases

For long COVID, the terrain is even rougher. Researchers are best able to address prevention when they understand a disease’s triggers, the source of its symptoms, and who’s most at risk. That intel provides a road map, pointing them toward specific bodily systems and interventions. The potential causes of COVID, though, remain murky, says Adrian Hernandez, a cardiologist and clinical researcher at Duke. Years of research have shown that the condition is quite likely to comprise a cluster of diverse syndromes with different triggers and prognoses, more like a category (e.g., “cancer”) than a singular disease. If that’s the case, then a single preventive treatment shouldn’t be expected to cut its rates for everyone. Without a universal way to define and diagnose the condition, researchers can’t easily design trials, either. Endpoints such as hospitalization and death tend to be binary and countable. Long COVID operates in shades of gray.

Still, some scientists might be making headway with vetted antiviral drugs, already known to slash the risk of developing severe COVID-19. A subset of long-COVID cases could be caused by bits of virus that linger in the body, prompting the immune system to wage an extended war; a drug that clears the microbe more quickly might lower the chances that any part of the invader sticks around. Paxlovid, which interferes with SARS-CoV-2’s ability to copy itself inside of our cells, fits that bill. “The idea here is really nipping it in the bud,” says Ziyad Al-Aly, a clinical epidemiologist and long-COVID researcher at Washington University in St. Louis, who led the recent Paxlovid work.

Paxlovid has yet to hit the scientific jackpot: proof from a big clinical trial that shows it can prevent long COVID in newly infected people. But Al-Aly’s study, which pored over the electronic medical records of more than 56,000 high-risk patients, offers some early optimism. People who took the pills, he and his colleagues found, were 26 percent less likely to report lingering symptoms three months after their symptoms began than those who didn’t.

Read: Inside the mind of an anti-Paxxer

The pills’ main benefit remains the prevention of severe, acute disease. (In the recent study, Paxlovid-takers were also 30 percent less likely to be hospitalized and 48 percent less likely to die.) Al-Aly expects that the drug’s effectiveness at preventing long COVID—if it’s confirmed in other populations—will be “modest, not huge.” Though the two functions could yet be linked: Some long-COVID cases may result from severe infections that damage tissues so badly that the body struggles to recover. And should Paxlovid’s potential pan out, it could help build the case for testing other SARS-CoV-2 antivirals. Al-Aly and his colleagues are currently working on a similar study into molnupiravir. “The early results are encouraging,” he told me, though “not as robust as Paxlovid.” (Another study, run by other researchers, that followed hospitalized COVID patients found those who took remdesivir were less likely to get long COVID, but a later randomized clinical trial didn’t bear that out.)

A clinical trial testing Paxlovid’s preventive potency against long COVID is still needed. Kit Longley, a spokesperson for Pfizer, told me in an email that the company doesn’t currently have one planned, though it is “continuing to monitor data from our clinical studies and real-world evidence.” (The company is collaborating with a research group at Stanford to study Paxlovid in new clinical contexts, but they’re looking at whether the pills might treat long COVID that’s already developed. The RECOVER trial, a large NIH-funded study on long COVID, is also focusing its current studies on treatment.) But given the meager uptake rates for Paxlovid even among those in high-risk groups, Al-Aly thinks his new data could already serve a useful purpose: providing people with extra motivation to take the drug.

The case for adding metformin to the anti-COVID tool kit might be a bit muddier. The drug isn’t the most intuitive medication to deploy against a respiratory virus, and despite its widespread use among diabetics, its exact effects on the body remain nebulous, says Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital. But there are many reasons to believe it might be useful. Some research has shown that metformin can mess with the manufacture of viral proteins inside of human cells, Bramante told me, which may impede the ability of SARS-CoV-2 and other pathogens to reproduce. The drug also appears to rev up the disease-dueling powers of certain immune cells, and to stave off inflammation. Studies have shown that metformin can improve responses to certain vaccinations in humans and rodents, and researchers have found that people taking the drug seem less likely to get seriously sick from influenza. Even the diabetes-coronavirus connection may not be so tenuous: Metabolic disease is a risk factor for severe COVID; infection itself can put blood-sugar levels on the fritz. It’s certainly plausible that having a metabolically altered body, Schultz-Cherry told me, could make infections worse.

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

But the evidence that metformin helps prevent long COVID remains sparse. Carolyn Bramante, the scientist who led the metformin study, told me that when her team first set out in 2020 to investigate the drug’s effects on SARS-CoV-2 infections in a randomized, clinical trial, long COVID wasn’t really on their radar. Like many others in their field, they were hoping to repurpose established medicines to keep infected people out of the hospital; early studies of metformin—as well as the two other drugs in their trial, the antidepressant fluvoxamine and the antiparasitic ivermectin—hinted that they’d work. Ironically, two years later, their story flipped around. A large analysis, published last summer, showed that none of the three drugs were stellar at preventing severe COVID in the short term—a disappointing result (though Bramante contends that their data still indicate that metformin does some good). Then, when Bramante and her colleagues examined their data again, they found that study participants that had taken metformin for two weeks around the start of their illness were 42 percent less likely to have a long-COVID diagnosis from their doctor nearly a year down the road. David Boulware, an infectious-disease physician who helped lead the work, considers that degree of reduction pretty decent: “Is it 100 percent? No,” he told me. “But it’s better than zero.”

Metformin may well prove to prevent long COVID but not acute, severe COVID (or vice versa). Plenty of people who never spend time in the hospital can still end up developing chronic symptoms. And Iwasaki points out that the demographics of long-haulers and people who get severe COVID don’t really overlap; the latter skew older and male. In the future, early-infection regimens may be multipronged: antivirals, partnered with metabolic drugs, in the hopes of keeping symptoms both mild and short-lived.

But researchers are still a long way off from delivering that reality. It’s not yet clear, for instance, whether the drugs work additively when combined, Boulware told me. Nor is it a given that they’ll work across different demographics—age, vaccination status, risk factors, and more. Bramante and Boulware’s study cast a decently wide net: Although everyone enrolled in the trial was overweight or obese, many were young and healthy; a few were even pregnant. The study was not enormous, though—about 1,000 people. It also relied on patients’ individual doctors to deliver long-COVID diagnoses, likely leading to some inconsistencies, so other studies that follow up in the future could find different results. For now, this isn’t enough to “mean we should run out and use metformin,” Schultz-Cherry, who has been battling long COVID herself, told me.

Other medications could still fill the long-COVID gaps. Hernandez, the Duke cardiologist, is hopeful that one of his ongoing clinical trials, ACTIV-6, might provide answers soon. He and his team are testing whether any of several drugs—including ivermectin, fluvoxamine, the steroid fluticasone, and, as a new addition, the anti-inflammatory montelukast—might cut down on severe, short-term COVID. But Hernandez and his colleagues, Naggie among them, appended a check-in at the 90-day mark, when they’ll be asking their patients whether they’re experiencing a dozen or so symptoms that could hint at a chronic syndrome.

That check-in questionnaire won’t capture the full list of long-COVID symptoms, now more than 200 strong. Still, the three-month benchmark could give them a sense of where to keep looking, and for how long. Hernandez, Naggie, and their colleagues are considering whether to extend their follow-up period to six months, maybe farther. The need for long-COVID prevention, after all, will only grow as the total infection count does. “We’re not going to get rid of long COVID anytime soon,” Iwasaki told me. “The more we can prevent onset, the better off we are.”

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Katherine J. Wu

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January 19, 2023
What Does It Mean to Care About COVID Anymore?

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After nearly three years of constantly thinking about COVID, it’s alarming how easily I can stop. The truth is, as a healthy, vaxxed-to-the-brim young person who has already had COVID, the pandemic now often feels more like an abstraction than a crisis. My perception of personal risk has dropped in recent months, as has my stamina for precautions. I still care about COVID, but I also eat in crowded cafés and go mask-free at parties.

Heading into the third pandemic winter, things have changed. Most Americans seem to have tuned out COVID. Precautions have virtually disappeared; except for in the deepest-blue cities, wearing a mask is, well, weird. Reported cases are way down since the spring and summer, but perhaps the biggest reason for America’s behavioral let-up is that much of the country sees COVID as a minor nuisance, no more bothersome than a cold or the flu.

And to a certain degree, they’re right: Most healthy, working-age adults who are up-to-date on their vaccinations won’t get severely ill—especially now that antivirals such as Paxlovid are available. Other treatments can help if a patient does get very sick. “People who are vaccinated and relatively healthy who are getting COVID are not getting that sick,” Lisa Lee, an epidemiologist at Virginia Tech, told me. “And so people are thinking, Wow, I’ve had COVID. It wasn’t that bad. I don’t really care anymore.”

Still, there are many reasons to continue caring about COVID. About 300 people are still dying every day; COVID is on track to be the third-leading cause of death in the U.S. for the third year running. The prospect of developing long COVID is real and terrifying, as are mounting concerns about reinfections. But admittedly, these sometimes manifest in my mind as a dull, omnipresent horror, not an urgent affront. Continuing to care about COVID while also loosening up behaviors is an uncomfortable position to be in. Most of the time, I just try to ignore the guilt gnawing at my brain. At this point, when so few people feel that the potential benefit of dodging an infection is worth the inconvenience of precautions, what does it even mean to care about COVID?

Read: Hundreds of Americans will die from COVID today

In an ideal epidemiological scenario, everyone would willingly deploy the full arsenal of COVID precautions, such as masking and forgoing crowded indoor activities, especially during waves. But that kind of all-out response no longer makes sense. “It’s probably not realistic to expect people to take precautions every time, perpetually, or even every winter or fall, unless there is a particularly concerning reason to do that,” Jennifer Nuzzo, an epidemiologist at Brown University, told me.

But, now more than ever, we must remember that COVID is not just a personal threat but a community one. For older and immunocompromised people, the risks are still significant. For example, people over 50 account for 93 percent of COVID-related deaths in the U.S., even though they represent just 35.7 percent of the population. As long as the death rate remains as high as it is, caring about COVID should mean orienting precautions to protect them. This idea has been around since the pandemic began, but its prominence faded as Americans put their personal health first. “If you’re otherwise healthy, it’s so easy just to think about yourself,” Lee said. “We have to think very carefully about that other part of infectious disease, which is the part where we can potentially hurt other people.”

Orienting behavior in this way gives low-risk people a way to care about COVID that doesn’t entail constant masking or skipping all indoor activities: They can relax when they know they aren’t going to encounter vulnerable people. Like the productivity adage “work smarter, not harder,” this perspective allows people to take precautions strategically, not always. In practice, all it takes is some foresight. If you don’t live with vulnerable people, make it second nature to ask: Will I be seeing vulnerable people anytime soon? If the answer is no, do whatever you’re comfortable with given your own risk. If you are a healthy 30-something who lives alone, going to a Friendsgiving with other people your age is different from spending Thanksgiving dinner with parents and grandparents.

If you will be seeing someone vulnerable, the most straightforward way to avoid giving them COVID is to avoid getting infected yourself, which means wearing a good mask in public settings and minimizing your interactions with others the week before, in what some experts have called a “mini-quarantine.” Not everyone has that luxury: Parents, for example, have to send their kids to school.

Spontaneous interactions with vulnerable people are trickier to plan for, but they follow the same principle. On a crowded bus, for example, “there’s no question that if you’re close enough to someone who could be hurt by getting COVID and you could have it, then, yeah, a mask is the way to go,” Lee said. Of course, it isn’t always possible to know when someone is high-risk; young people, too, can be medically vulnerable. There’s no clear guidance for those situations, but remaining cautious doesn’t require much effort. “Carry a mask with you,” Lee said. “It’s not a big lift.”

Get boosted—if not for yourself, then for them. Just 11.3 percent of eligible Americans have gotten the latest, bivalent shot, which potentially reduces your chances of getting COVID and passing it along. It also means getting tested, so you know when you’re infectious, and being aware of respiratory symptoms—of any kind. Alongside COVID, the flu and RSV are putting many people in the hospital, especially the very young and the very old. No matter how low your personal risk, if you have symptoms, avoiding transmission is crucial. “A reasonable thing to prioritize is: If you have symptoms, take care to prevent it from spreading,” Caitlin Rivers, an epidemiologist at Johns Hopkins University, told me.

Read: It’s a bad time to be a booster slacker

As we move away from a personal approach to COVID, we have an opportunity to expand the idea of what caring looks like. Low-risk people can, and should, take an active role in bolstering the protection of vulnerable people they know. In practical terms, this means ensuring that people in your life who are over 50—especially those over 65—are boosted and have a plan to get Paxlovid if they fall sick, Nuzzo said. “I think our biggest problem right now is that not everybody has enough access to the tools, and that’s a place where people can help.” She noted that she is particularly concerned about older people who struggle to book vaccine appointments online. Caring “doesn’t mean abstaining, per se. It means facilitating. It means enabling and helping people in your community.” This holiday season, caring could mean sitting down at a computer to make Grandma’s booster appointment, or driving her to the drugstore to get it.

If you have lost your motivation to care about COVID, you might find it in the people you love. I didn’t feel a personal need to wear a mask at the concert I attended yesterday, but I did it because I don’t want to accidentally infect my partner’s 94-year-old grandfather when I see him next week. To have this experience of the pandemic is a privilege. Many don’t have the option to stop caring, even for a moment.

Barring another Omicron-esque event, we thankfully won’t ever return to a moment where Americans obsess over COVID en masse. But this virus isn’t going away, so we can’t escape having a population that is split between the high-risk minority and the low-risk majority. Rethinking what it means to care allows for a more nuanced and liveable idea of what responsible behavior looks like. Right now, Nuzzo told me, the language we use to describe one’s position on COVID is “black-and-white, absolutist—you either care or you don’t.” There is space between those extremes. At least for now, it’s the only way to compromise between the world we have and the world we want.

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Yasmin Tayag

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November 21, 2022
A Simple Rule for Planning Your Fall Booster Shot

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

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

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

If you haven’t had an Omicron infection:

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

Read: The pandemic’s soft closing

If you have had an Omicron infection:

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

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

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

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

If you had an Omicron infection this summer:

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

If you’re at high risk:

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

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

If you want to wait and see:

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

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

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Rachel Gutman-Wei

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August 27, 2022