Immune changes, persistent spike protein seen in people with PVS

People with post-vaccination syndrome (PVS), a rare condition following receipt of COVID-19 jabs, exhibit distinct immunological patterns, including the reappearance of the dormant Epstein-Barr virus (EBV) and persistence of SARS-CoV-2 spike protein in the blood, according to new research.

Compared with healthy controls, the immune cell populations of people with PVS had lower levels of effector CD4 T cells and higher levels of CD8 T cells that secrete tumour necrosis factor (TNF), wrote study author Dr Akiko Iwasaki and colleagues from Yale University School of Medicine in New Haven, Connecticut, US in a non-peer-reviewed paper. [medRxiv 2025;doi.org/10.1101/2025.02.18.25322379]

“It’s not like we sought to determine what made people sick. It’s the first glimpse at what may be going on in this population with PVS,” said Iwasaki.

A constellation of side effects

COVID-19 vaccines have saved millions of lives, but a small fraction of vaccine recipients have reported a constellation of side effects, including fatigue, exercise intolerance, brain fog, tinnitus, and dizziness, referred to as PVS.

Between December 2022 and November 2023, Iwasaki and her team explored potential pathobiological features associated with this rare condition in a cross-sectional study of 42 individuals with PVS and 22 healthy controls without it enrolled in the Yale LISTEN study. People with the syndrome generally have poorer health.

The most frequent symptoms reported in the PVS cohort were excessive fatigue (85 percent), tingling and numbness (80 percent), exercise intolerance (80 percent), brain fog (77.5 percent), difficulty concentrating or focusing (72.5 percent), trouble falling or staying asleep (70 percent), neuropathy (70 percent), muscle aches (70 percent), anxiety (65 percent), tinnitus (60 percent), and burning sensations (57.5 percent).

Spike protein lasts longer

As the symptoms reported in PVS overlap with those of long COVID, Iwasaki’s team also analysed blood samples from 134 people with long COVID and 134 healthy controls.

Just like people with long COVID, those with PVS had a reactivation of the EPV. A subset of PVS patients also had higher levels of circulating spike protein in the blood. The S1 subunit of the spike protein was positive in plasma up to 709 days post-exposure, which Iwasaki described as “surprising.”

He said the mRNA used in the vaccines was unlikely the source of the persistent spike protein. “Something else is allowing this sort of late-phase expression of spike protein, and we don’t know what that is,” she said. “However, other studies have shown that spike protein alone can induce fibrin clots and neuroinflammation.”

More studies needed

The study is small, and PVS is a heterogeneous disorder. However, further studies in a larger patient group are warranted despite these limitations, said Dr Gregory Poland, president of the Atrial Health and Research Institute in New York City, New York, US.

“My clinical impression is that PVS is real,” he said. “Collectively, the finding adds to the growing body of literature and clinical experience suggesting that in rare cases, mRNA-based COVID vaccines can induce immune, autoimmune, viral reactivation, and other perturbations in susceptible individuals. We need more studies of carefully defined and phenotyped individuals to support these findings.”