For the vast majority of individuals, COVID-19 vaccines have proven safe and effective, saving countless lives during the pandemic. However, a small percentage of people experience chronic symptoms that can persist for months or even years, a condition now referred to as “post-vaccination syndrome” (PVS).

Recent findings by Yale researchers offer early insights into the potential causes of this syndrome, providing hope for future treatments.

Early discoveries

In a preliminary study, the Yale team identified “potential immunological patterns” unique to individuals with PVS. These patterns include lower levels of certain white blood cells and higher levels of inflammatory immune cells. The researchers analyzed blood samples from 42 participants with PVS symptoms and compared them to 22 individuals without symptoms.

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“This work is still in its early stages, and we need to validate these findings,” noted Akiko Iwasaki, Sterling Professor of Immunobiology at Yale School of Medicine. “But this is giving us some hope that there may be something that we can use for diagnosis and treatment of PVS down the road.”

Symptoms of post-vaccination syndrome

People with PVS often experience symptoms such as excessive fatigue, exercise intolerance, brain fog, insomnia, and dizziness. These symptoms typically develop within a day or two of vaccination and can worsen over time.

“It’s clear that some individuals are experiencing significant challenges after vaccination. Our responsibility as scientists and clinicians is to listen to their experiences, rigorously investigate the underlying causes, and seek ways to help,” emphasized Harlan Krumholz, professor of cardiology at Yale School of Medicine.

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Biological underpinnings

The study revealed that individuals with PVS who had never contracted COVID-19 had lower levels of antibodies against the SARS-CoV-2 spike protein, likely due to receiving fewer vaccine doses. Additionally, some participants with PVS showed persistent levels of the SARS-CoV-2 spike protein in their blood, even more than 700 days after vaccination.

“We don’t know if the level of spike protein is causing the chronic symptoms, because there were other participants with PVS who didn’t have any measurable spike protein—but it could be one mechanism underlying this syndrome,” Iwasaki explained. Other potential factors contributing to PVS include autoimmunity, tissue damage, and reactivation of the Epstein-Barr virus (EBV).

Moving forward

While the study provides promising leads, it is crucial to conduct further research to understand PVS and develop effective treatments fully. “We’re only just starting to make headway in understanding PVS,” noted Krumholz. “Every medical intervention carries some risk, and it’s important to acknowledge that adverse events can occur with vaccines”.

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Dr. Marc Siegel, clinical professor of medicine at NYU Langone Health, emphasized that PVS is a real condition that warrants further investigation: “Post-vaccination syndrome is real, and has been found [to occur] from many vaccines, including COVID.”

The focus now shifts to rigorous scientific inquiry and compassionate support for those affected by PVS. As Siegel pointed out, “This needs to be further studied in terms of understanding how common prolonged COVID-19 vaccine side effects are and how to predict them and treat them”.

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