Rare Syndrome After COVID Vaccines Described

People who experienced rare long-term adverse events after COVID-19 vaccination often had neurologic symptoms, survey data showed.

Among 241 people who self-reported a post-vaccination syndrome (PVS), the five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%), reported Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, and co-authors in a paper posted on the preprint server medRxiv. The paper has not been peer-reviewed.

“The study is the largest investigation of the experience of people reporting a chronic, debilitating condition that began soon after a COVID-19 vaccination,” Krumholz told MedPage Today.

“It raises awareness about what these individuals are experiencing and points attention to the need for more studies to understand what is underlying this condition and how to relieve suffering,” he continued. “These people are not anti-vaxxers — they were all vaccinated — but because of politics, many have had the experience of being dismissed and ignored.”

Ongoing symptoms after COVID vaccines are rarely studied. “Even the definition of post-vaccination syndrome is in flux, but a working definition could be symptoms that begin with a week of a vaccination and persist for at least 2 months,” Krumholz said.

Last year, an NIH-funded study on medRxiv evaluated new neuropathic symptoms in 23 people that started soon after they received a COVID vaccine. About half (52%) of the 23 participants had objective evidence of small-fiber peripheral neuropathy; of those, 58% who were treated with oral corticosteroids had complete or near-complete improvement after 2 weeks. Some participants improved without immunotherapy.

Case reports suggested post-vaccine neuropathy and tinnitus may be treated with plasma exchange. Postural orthostatic tachycardia syndrome (POTS) also has been diagnosed after COVID vaccines.

Reports to the Vaccine Adverse Event Reporting System (VAERS) after COVID vaccination include a variety of neurologic and systemic manifestations, Krumholz and co-authors noted. These symptoms may share mechanisms with post-COVID complications, they observed.

“Importantly, immune-mediated neurological adverse events post-vaccination are rare and often less severe than those that follow actual infection,” they wrote.

Krumholz and colleagues surveyed 241 adults who self-reported PVS after COVID-19 vaccination and who joined the online LISTEN study from May 2022 to July 2023. People with long COVID were excluded from the study.

Median participant age was 46. Most were women (80%), white (87%), and from the U.S. (88%). About half (55%) received the Pfizer-BioNTech (Comirnaty) vaccine and 37% had the Moderna (Spikevax) shot. A third (34%) said they had SARS-CoV-2 infection at least once.

PVS symptom onset occurred within a median of 3 days of the index vaccination. Symptoms began after the first, second, third, and fourth (or more) vaccinations for 44%, 33%, 14%, and 9% of participants, respectively.

Participants completed surveys from November 2022 and July 2023, a median of 595 days after vaccination. From a list of 96 symptoms, they were asked to identify health conditions they had as a result of vaccine injury. They also reported their self-perceived health status on a 5-point scale of excellent, very good, good, fair, or poor.

In addition, participants rated their quality of life with the Euro-QoL visual analogue scale (EQ-VAS; a score of 100 represented the best), and reported symptom severity by rating symptoms on their worst days, with 0 meaning trivial illness and 100 being unbearable.

The median number of symptoms attributed to PVS was 22. Overall, 44% rated their current health as fair or poor. The median EQ-VAS score was 50; in people without previous comorbidities, it was 52. Participants reported a median symptom severity of 80 on their worst days.

The median number of treatments tried was 20. The most common prescription therapies were oral steroids (48%), gabapentin (25%), low-dose naltrexone (20%), ivermectin (18%), propranolol (11%), and bronchodilators (11%).

The most common non-drug treatments included limiting exercise or exertion (51% of participants), quitting alcohol or caffeine (44%), hydration and increasing salt intake (44%), and intermittent fasting (39%).

In the week before completing the survey, most participants said they felt unease (93%), fearfulness (82%), or overwhelmed by worries (81%), and reported feelings of helplessness (80%), anxiety (76%), depression (76%), or hopelessness (72%) at least once.

This report is a step toward acknowledging the effects of PVS, Krumholz noted. “The next step is to correlate what these people are experiencing with deep investigations of immune function,” he said. The LISTEN study continues to recruit participants, he added.

The study had limitations; participants were self-referred and symptoms were self-reported. “The participants are not representative, so it is not possible to estimate the incidence or who might be most susceptible to this condition,” the researchers acknowledged.