COVID-19 vaccines have saved millions of lives, and the world is gearing up for a new round of boosters. But like all vaccines, those targeting the coronavirus can cause side effects in some people, including rare cases of abnormal blood clotting and heart inflammation. Another apparent complication, a debilitating suite of symptoms that resembles Long Covid, has been more elusive, its link to vaccination unclear and its diagnostic features ill-defined. But in recent months, what some call Long Vax has gained wider acceptance among doctors and scientists, and some are now working to better understand and treat its symptoms.
“You see one or two patients and you wonder if it’s a coincidence,” says Anne Louise Oaklander, a neurologist and researcher at Harvard Medical School. “But by the time you’ve seen 10, 20,” she continues, trailing off. “Where there’s smoke, there’s fire.”
Cases seem very rare—far less common than Long Covid after infection. Symptoms can include persistent headaches, severe fatigue, and abnormal heart rate and blood pressure. They appear hours, days, or weeks after vaccination and are difficult to study. But researchers and clinicians are increasingly finding some alignment with known medical conditions. One is small fiber neuropathy, a condition Oaklander studies, in which nerve damage can cause tingling or electric shock–like sensations, burning pain, and blood circulation problems. The second is a more nebulous syndrome, with symptoms sometimes triggered by small fiber neuropathy, called postural orthostatic tachycardia syndrome (POTS). It can involve muscle weakness, swings in heart rate and blood pressure, fatigue, and brain fog.
Patients with postvaccination symptoms may have features of one or both conditions, even if they don’t meet the criteria for a diagnosis. Both are also common in patients with Long Covid, where they’re often attributed to an immune overreaction.
Although more researchers are now taking Long Vax seriously, regulators in the United States and Europe say they have looked for, but have not found, a connection between COVID-19 vaccines and small fiber neuropathy or POTS. “We can’t rule out rare cases,” says Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research, which oversees vaccines. “If a provider has somebody in front of them, they may want to take seriously the concept [of] a vaccine side effect,” he says. But Marks also worries about “the sensational headline” that could mislead the public, and he emphasizes that vaccine benefits far outweigh any risks.
Despite the uncertainties, German Minister of Health Karl Lauterbach acknowledged in March that though rare, Long Covid–like symptoms after vaccination are a real phenomenon. He said his ministry was working to organize funding for studies, although none has been announced so far.
Researchers studying these complications also worry about undermining trust in COVID-19 vaccines. Harlan Krumholz, a cardiologist at Yale University, says concern that the antivaccine movement would seize on any research findings made him hesitant at first to dive in. But about a year ago he and Yale immunologist Akiko Iwasaki began to welcome postvaccination patients into a new study called LISTEN that also includes Long Covid patients. Among other things, it aims to correlate symptoms with immune cell patterns in blood samples.
“I’m persuaded that there’s something going on” with these side effects, Krumholz says. “It’s my obligation, if I truly am a scientist, to have an open mind and learn if there’s something that can be done.”
SCIENCE FIRST wrote about these health concerns in January 2022, describing efforts by scientists at the National Institutes of Health to study and treat affected individuals. A study including 23 people was posted as a preprint in May 2022 but never published. Following Science’s story, almost 200 people contacted the journal sharing their postvaccination symptoms.
Research has since proceeded slowly. This is “a challenging outcome to monitor,” Tom Shimabukuro of the U.S. Centers for Disease Control and Prevention told a government advisory committee in January. Still, more than two dozen case studies have accumulated describing POTS or small fiber neuropathy following a COVID-19 shot, regardless of the vaccine manufacturer.
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