Long-Haulers Are Pushing the Limits of COVID-19 Vaccines

People with long COVID were left out of vaccine trials. They are now navigating the new shots on their own.

A health-care worker prepares a Moderna COVID-19 vaccine in San Francisco, March 1, 2021
Mike Kai Chen / The New York Times / Redux

When I spoke with Letícia Soares on March 12, day 335 of her battle with COVID-19, she was celebrating an anniversary of sorts. It had been 11 months to the day since the start of her illness—an unrelenting sickness that has pinwheeled her through more than 65 symptoms, including fatigue, nausea, migraines, diarrhea, chest pain, hair loss, asthma, abdominal pain, brain fog, heart problems, and painful inflammation in both eyes. When the vaccine rollout began, she and her partner, who also has long COVID, couldn’t help but worry. “Is it safe?” she recalled thinking at the time. “Could it exacerbate our symptoms?”

The clinical trials, for any of the vaccines, had no answers: None set out to study the safety and efficacy of the shots in this population. And although long COVID is a chronic and debilitating condition, it is not among the chronic and debilitating conditions that currently qualify someone for a vaccine. Soares and her partner intend to get their shots when they become eligible. Still, when news of the vaccines’ success broke, “we didn’t know what it meant for us,” Soares, a 36-year-old biologist at Western University in Ontario, Canada, told me. “There was no empirical evidence to reduce our anxiety.”

Many long-haulers are still lining up for vaccination, in hope of guarding against a future tussle with the coronavirus and a more severe bout of disease. (Early evidence hints that COVID-19 survivors do produce a strong immune response to the virus, but might need the extra jolt offered by vaccines to keep their defenses high.) Now, as more shots roll out, a second potential perk has emerged: A scattering of long-haulers report that their COVID-19 symptoms have mysteriously faded after their shots—an astounding and unexpected pattern that’s captured the attention of experts worldwide.

Stories of symptoms that subside after the shots are intriguing, experts told me. But no clinical trials have tested whether the vaccines can act as makeshift therapeutics for long COVID, either. It’s still unclear how common these ebbs in illness are, or how fleeting they might be. In patient-led surveys, at least as many long-haulers are reporting no postvaccination change in symptoms; a small percentage said that the shots have so far made their illness worse.

Long COVID, with its constellation of debilitating, life-altering symptoms, is one of the most serious outcomes of a coronavirus infection. But it remains one of the least understood parts of the pandemic. A year into the greatest global health crisis in a century, scientists still have not settled on a consensus definition for long COVID, let alone a standard set of tests or treatments. Now long-haulers are tackling one of the biggest data vacuums yet: the collision of their condition with vaccines.

If all goes well, vaccines could chip away at the long-hauler population on two fronts: preventing long COVID, and perhaps bringing some cases to an end. But as the world rushes toward the promise of a finish line, the science of long COVID once again lags behind. Until that gap is closed, our race against the virus cannot be won.

My colleague Ed Yong was one of the first to report on long COVID, in June. In the nine months since, the condition has gained international recognition and sparked a small but growing number of efforts to scientifically suss out its causes, including several that will be funded by the National Institutes of Health. Without firm answers, progress on palliatives and preventives for the disease will be halting and patchwork; in many trials studying treatments for coronavirus infections, long-COVID patients have simply been left out.

That’s also been the case for immunizations. When many vaccine developers’ clinical trials began last spring, long COVID wasn’t yet widely known, making it difficult to enroll people who had begun to suffer its symptoms or to check whether the shots affected the risk of contracting the condition. The result was erasure: Not asking was easier. While billions of people around the globe have seen themselves reflected in vaccine trials and their dazzling success, long-haulers have so far been offered only a distant window into someone else’s reality.

That oversight may have opened up a big gap in the armor that vaccines are meant to offer. Recent studies suggest that 10 to 30 percent of people with documented coronavirus cases have experienced long-term consequences. Some lingering impacts are the products of severe coronavirus infections, which can leave organs riddled with damage that lasts months. In this population, “I’m optimistic that the vaccines will make a big dent,” Lekshmi Santhosh, a pulmonologist and long-COVID researcher at UC San Francisco, told me. But vaccines are less likely to block the mildest forms of disease, muddying the forecast for long-COVID cases that sprout from more silent infection. Many long-haulers never became sick enough to be hospitalized; some even started out with mild or symptomless infections that only later blossomed bafflingly into debilitating disease.

Akiko Iwasaki, an immunologist at Yale, has proposed three explanations for long COVID. In one, the coronavirus might linger in the nooks and crannies of some long-haulers’ bodies, evading ready detection, but still replicating enough to raise the ire of the immune system. In another, fragments of viral genes or proteins—though not infectious themselves—might remain adrift in the system, duping immune cells into launching a prolonged and unnecessarily vigorous attack. Or, perhaps, no trace of the pathogen is left; rather, its transient presence sets the immune system askew, leaving disoriented cells squabbling among themselves. Researchers haven’t yet teased these very plausible ideas apart; these hypotheses also aren’t mutually exclusive.

A vaccine could, in theory, combat all of Iwasaki’s proposed scenarios by simply thwarting the virus. “If you’re not even getting infected,” she told me, the chances of long COVID disappear. Even people who aren’t rendered impervious to the virus might still have enough immunological juice to pen the pathogen in place. Researchers think some cases of long COVID could involve the virus spreading unchecked throughout the body, infiltrating tissues where it might not belong. Sequestering it early could head off its more insidious effects, says Rachel Rutishauser, an immunologist at UCSF. But none of that has yet been confirmed.

Foggier still is the potential impact of vaccines on existing long-haulers. Many long-COVID survivors are understandably nervous about introducing into their body something reminiscent of the pathogen that catalyzed their illness—something that could, in theory, rouse immune cells into doubling down on their overzealous attacks. “There’s a lot of anxiety,” Denyse Lutchmansingh, a critical-care physician and long-COVID researcher at Yale, told me. “Some of these patients feel so awful that you really do not want to do something that might trigger them.”

The vaccines have also been linked with a bevy of side effects that, while not inherently unsafe, echo the fevers, aches, and fatigue that long-haulers often experience. People who have already encountered the virus also seem more likely to have an initially rough go with their shots. Una Osato, a 38-year-old New York performer, writer, and educator who has had COVID-19 for more than a year, spent several days in the vise grip of flu-like symptoms after she received Pfizer’s vaccine. “It was almost a reprise of my [initial] COVID experience,” Osato told me. But she has no regrets about getting her vaccine. “I would have done it again,” she said.

A small number of long-haulers might experience a longer dip in well-being after their shots, or mixed outcomes in improvement. Andrew Gold, a 64-year-old chef and cookbook editor in New York, felt some symptoms worsen after he received the Pfizer vaccine. His fatigue, shortness of breath, and aches became more severe; his blood-oxygen levels dropped. His sense of taste and smell, which had recently started to creep back, retreated once again. But he’s focusing on the positives: His erratic heartbeat has quieted slightly, and his fevers have lessened a notch. The day he got his second dose, he walked home with a bag of groceries, without stopping, for the first time in eight months.

John Wherry, an immunologist at the University of Pennsylvania, told me he thinks unilateral deteriorations will be the minority. Although viruses and vaccines share features in common, the crucial differences that make the shots safe will also reduce the chances that they’ll stoke the symptomatic flames of long COVID. Many pathogens, including the new coronavirus, have evolved to purposefully discombobulate the immune system in various ways, allowing them to batter the body with ease. Vaccines, which contain no active viruses, don’t run this risk.

One small study, not yet peer-reviewed, seems to bolster this idea. Researchers tracked the symptoms of 66 previously hospitalized long-COVID patients for more than eight months, 44 of whom received a vaccine earlier this year. Most of the shot recipients battled a brief bout of flu-like symptoms after their vaccination. But the side effects melted away after a couple of days. A month after the inoculations, the researchers found no evidence that the shots had consistently worsened people’s long-term symptoms. “I think there’s increasing evidence that these vaccines are not causing dramatic harm” to long-haulers, Fergus Hamilton, an infectious-disease specialist at the University of Bristol, in England, and the study’s lead author, told me.

For many long-haulers, the hope that vaccines won’t exacerbate their illness might have been enough to sway them into getting their shots. But in recent weeks, hundreds of recently vaccinated long-COVID patients around the world have reported feeling not just a lack of bad side effects from their shots, but immense relief from their symptoms. For some, the improvements have already endured for weeks or months—the most extended calm some of them have had since their sickness began.

When Kim Wills-Rinaldi, a 58-year-old geriatric-and-palliative-care social worker in Connecticut, first received a chance at vaccination in January, “I completely panicked,” she told me. She had spent the past 10 months dueling COVID-19 symptoms, developing shingles, arthritis, and rashes; her hair had fallen out in clumps. “I kept thinking, I’ve been so sick for a year. What if this makes me really bad again?” But two days after receiving her first dose of the Pfizer vaccine on March 12, Wills-Rinaldi awoke and found that almost all of her symptoms had vanished. “For me, this is like a miracle,” she said.

Wills-Rinaldi hasn’t yet gotten her second shot, and there’s no telling whether the respite will stick. Most immunologists are still hesitant to draw firm conclusions about how common these remissions might be, but the idea of using vaccines as therapeutics “isn’t new,” Sulggi Lee, an infectious-disease physician and immunologist at UCSF, told me. A number of therapeutic vaccines are being developed against HIV and certain cancers, in the hope that they will rev up immune cells to purge roaming pathogens, or destroy aberrant or infected cells. If typical vaccines are study guides given to students before big exams, therapeutic vaccines are a next-best resource—open-book tests.

Still, speculating on what soothes long COVID layers the theoretical on top of the theoretical. In a recent blog post on Medium, Iwasaki, the Yale immunologist, expanded on her three original hypotheses, appending explanations of how the vaccine might tackle each of them.

In long-COVID survivors whose immune systems have struggled to evict bits of the virus, Iwasaki told me, the vaccines might marshal a wave of antibodies and T cells—some of the body’s most essential fighters—that boots out these unwanted tenants and their scrappy remains. Alternatively, the vaccines could restore balance to an unhinged immune system, refocusing its resources on guarding against pathogens instead of attacking healthy tissues. There’s precedent for this, Iwasaki said: Some treatments for autoimmune conditions, such as multiple sclerosis, counterintuitively involve riling up other branches of the immune system. This last possibility is perhaps the most precarious, as it could be “a temporary suppression” of the long-haul condition, she told me. Lutchmansingh, at Yale, likened the idea to “a kick in the pants for the immune system.”

The emotional relief that many people feel after receiving their shots, and their confidence in the protection of vaccination, could also be helping long-haulers, Rutishauser, of UCSF, told me. The vaccine is “associated with a return to normalcy,” she said. The improvements documented so far shouldn’t be dismissed as a meaningless placebo effect, she added: Physical and psychological well-being can spur each other forward as some people’s sickness abates.

Long COVID has been “such a lonely place,” Kelly House, a 52-year-old long-hauler in North Carolina, told me. “You almost feel like, what’s wrong with you that you can’t get past this?” House’s fatigue and headaches, which have plagued her since July, retreated the morning after she received her first dose of the Pfizer vaccine on March 10, taking a hefty slice of self-doubt and confusion with them. “I finally have good news now,” she said.

Since the start of the pandemic, long-haulers have been navigating their own illness, paving paths for researchers to follow. Online support groups have swollen to many thousands of members, who have spearheaded efforts to bring recognition to their sickness. When some long-haulers first started to report that the vaccines had seemingly driven their symptoms into hiding, others rushed to immortalize those stories in data.

One patient-led survey, run by the filmmaker Gez Medinger, found that among 345 long-haulers—most of them in the United Kingdom—who said they had received their first dose of a COVID-19 vaccine at least two weeks earlier, roughly a third of respondents felt that their symptoms had improved. About a fifth of the participants felt worse, and half experienced no change. Diana Berrent, the founder of Survivor Corps, a long-COVID support group, told me that similar results emerged from her group’s survey, which is tracking the symptoms of about 850 vaccinated long-haulers and counting, some 40 percent of whom say their symptoms have waned post-vaccination. (Another 45 percent said their symptoms were unchanged, while 15 percent said they had worsened.) Hannah Davis, of Body Politic, another support group, is amassing similar accounts. The mood in the past few weeks, several long-haulers told me, has started to tip toward cautious buoyancy as stories trickle in, no two quite alike.

After spending 10 months with a steady drumbeat of fatigue, chest pain, congestion, shortness of breath, and burning body pain, Jean Bratman, 62, of Maryland, received her first dose of the Pfizer vaccine in January. The week after the shot, she took her first walk in three months. Now seven weeks out from her second dose, she is fully vaccinated—and for the first time in a year, “I feel nearly normal, almost symptom-free,” she said. “It’s wonderful.” In Seattle, Anne McCloskey, 54, rediscovered the taste of oranges and sushi—food that had, for the better part of a year, been colorful textures, devoid of flavor—after finishing her full course of Moderna’s vaccine in February. The shots stripped away her insomnia, heart problems, and cognitive issues that had caused her to forget her son’s birthday. Long COVID “felt like someone threw a weight on me and sunk me, like an anchor,” McCloskey told me. She is finally unmoored.

Still, the numbers collected in early surveys won’t necessarily be representative. Some of the experts I talked with said they weren’t seeing rates of improvement quite so high among their own patients. Most of the patients in the University of Bristol study, for instance, “did not experience a dramatic change” in their symptoms, Hamilton told me.

People’s postvaccination outcomes are “all over; it’s anecdotal,” Melissa Pinto, a nurse and long-COVID researcher at UC Irvine, told me. “We don’t even know what makes a person at risk for long COVID or how long COVID happens without a vaccine.” The shots, Pinto said, just add another perplexing variable to the jumble. “It’s a fool’s errand to try and quantify some of this yet,” Berrent, of Survivor Corps, told me. “We’re still qualifying it.” Even the best vaccines aren’t perfect preventives; they won’t be panaceas for ongoing disease, either.

Nevertheless, “there’s something kind of consistent in these reports,” Iwasaki told me. “I’m hopeful that there is something real underneath.” In the coming weeks, months, and years, researchers will try to home in on what that something is.

Certainly not all long-COVID survivors will experience vaccination in the same way. And the shots alone won’t magic away the scars of damaged tissue or the numbing heft of depression brought on by months of sickness. Many of the long-haulers I spoke with whose health had been ostensibly boosted by their shots said their thoughts had been consumed with the prospect of those benefits slipping away. Others who hadn’t experienced relief from their shots felt guilty that they hadn’t lived up to expectations. In New York, Osato has been flooded with messages from friends and family eager to spread the news of post-vaccine recoveries; she’s worked to gently tune it out. “I’ve needed to not focus on the possibility of my symptoms disappearing, because it sets me up to feel disappointed, sad, and hoping on what seems like a lottery,” she told me. Long COVID is not a monolith. Its origins and end points won’t be either.

For every long-hauler who has gotten a vaccine, there are still dozens more who haven’t. Soares, in Toronto, is one of them. As the vaccine rollout in her region continues, she is watching with a mix of optimism and trepidation. She and her partner spend their days in a delicate dance, searching for the rare moments in which they both feel well. Perhaps, Soares told me, a vaccine will put their life back on track.

But Soares isn’t betting on that possibility. What counts most, she told me, is getting the vaccine for what it was intended to do: protect against the virus itself, should she meet it again. Although what sits at the intersection of long COVID and vaccines is murky, Soares said, “my fear of reinfection is worse.”