The Covid-19 vaccine may have led to a constellation of side effects that includes fatigue, exercise intolerance, brain fog, tinnitus and dizziness, together referred to as “post-vaccination syndrome”, according to a small study.
The research suggested that some people with this syndrome appear to show distinct biological changes, among them differences in immune cells, the reawakening of a dormant Epstein-Barr Virus, and the persistence of a coronavirus protein in their blood.
The study was posted online last week but has not yet been published in a scientific journal.
“I want to emphasise that this is still a work in progress," said Akiko Iwasaki, an immunologist at Yale University who led the work.
“It’s not as if this study determined what’s making people sick,” she added, “but it’s the first kind of glimpse at what may be going on within these people.”
Independent experts noted that the findings were not conclusive on their own. Yet the results, from a scientific team known for rigorous work, suggest that post-vaccination syndrome deserves further scrutiny, they said.
“One of the most important things is that we get some attention to really shine a light on this and try to understand exactly what it is,” said John Wherry, director of the Institute for Immunology at the University of Pennsylvania. (Wherry has previously collaborated with Iwasaki’s team, but did not participate in this work.)
Thousands of people have said that Covid vaccines harmed them. But the fragmented healthcare system in the US complicates detection of uncommon side effects and has provided little clarity on the range of symptoms people might have experienced after a Covid shot.
The patchwork has also made it difficult to compare and collate self-reported anecdotes. The latest study is small, and the condition it is studying is “very heterogeneous”, said Dr Gregory Poland, emeritus editor of the journal Vaccine and president of Atria Research Institute.
“Despite these limitations, they found interesting data that need further study,” he said. “Much larger studies of very carefully defined and phenotyped individuals need to take place.”
Between December 2022 and November 2023, Iwasaki and her team collected blood samples from 42 people with post-vaccination syndrome and 22 healthy people without it. People with the syndrome were generally in poorer health than the average American, the researchers found.
When they analysed components of the immune system, those with post-vaccination syndrome had different proportions of some immune cells, compared with controls. It’s unclear what these differences might mean; the researchers did not link them to individual symptoms.
Because the symptoms reported by people with post-vaccination syndrome show considerable overlap with those of long Covid, the researchers also analysed blood from 134 people with long Covid and 134 healthy controls. Like people with long Covid, those with post-vaccination syndrome showed reactivation of Epstein-Barr virus, a virus that may lie dormant in the body and is linked to mononucleosis, multiple sclerosis and other conditions.
Some cases of long Covid are thought to result from the persistence of the spike protein of the coronavirus, resulting in a heightened state of inflammation in the body.
Iwasaki and her team found that people with post-vaccination syndrome had significantly higher plasma levels of the coronavirus spike protein than everyone else – including those with long Covid – from 26 to 709 days after receiving the vaccine.
She said the mRNA vaccines were unlikely to be the source of the protein so long after the shots were administered. “Something else is allowing this sort of late-phase expression of spike protein, and we don’t really know what that is,” she said.
Wherry suggested caution in interpreting that result. For example, it’s possible that some of the protein may result from undetected coronavirus infections. “I would like to see more data on this topic,” he said.
Still, he added, the lack of clear answers makes it even more important to continue to explore the issue.
“One of the things that maybe scientists got trapped into a little bit during the pandemic is this perception that we should have all the answers, and if we can’t give it a definitive answer, then we shouldn’t be talking about it,” he said. “I think that’s a mistake. We can’t say for certainty that this can’t happen.”
Study details
Immunological and antigenic signatures associated with chronic illnesses after Covid-19 vaccination
Bornali Bhattacharjee, Peiwen Lu, Akiko Iwasaki et al.
Summary
Covid-19 vaccines have prevented millions of Covid-19 deaths. Yet, a small fraction of the population reports a chronic debilitating condition after vaccination, often referred to as post- vaccination syndrome (PVS). To explore potential pathobiological features associated with PVS, we conducted a decentralised, cross-sectional study involving 42 PVS participants and 22 healthy controls enrolled in the Yale LISTEN study. Compared with controls, PVS participants exhibited differences in immune profiles, including reduced circulating memory and effector CD4 T cells (type 1 and type 2) and an increase in TNFα+ CD8 T cells. PVS participants also had lower anti-spike antibody titers, primarily due to fewer vaccine doses. Serological evidence of recent Epstein-Barr virus (EBV) reactivation was observed more frequently in PVS participants. Further, individuals with PVS exhibited elevated levels of circulating spike protein compared to healthy controls. These findings reveal potential immune differences in individuals with PVS that merit further investigation to better understand this condition and inform future research into diagnostic and therapeutic approaches.
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