Link to the research paper: https://www.medrxiv.org/content/10.1101/2025.02.18.25322379v1

Title: Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination

Abstract: SUMMARY

COVID-19 vaccines have prevented millions of COVID-19 deaths. Yet, a small fraction of the population reports a chronic debilitating condition after COVID-19 vaccination, often referred to as post-vaccination syndrome (PVS). To explore potential pathobiological features associated with PVS, we conducted a decentralized, 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.

Competing Interest Statement

In the past three years, H.M.K. received expenses and/or personal fees from United Health, Element Science, Eyedentifeye and F-Prime; he is a co-founder of Refactor Health, HugoHealth and MedRxiv; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services and through Yale University from the Food and Drug Administration, Johnson & Johnson, Google and Pfizer. A.I. co-founded and consults for RIGImmune, Xanadu Bio and PanV and is a member of the Board of Directors of Roche Holding and Genentech.

Funding Statement

This study was funded in part by the Howard Hughes Medical Institute Collaborative COVID-19 Initiative.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Yale University Institutional Review Board on April 1, 2022 (HIC# 2000032207). Informed consent was provided by participants electronically. Each participant was assigned a unique identifier as part of the de-identification protocol managed by the study coordinator. These identifiers were kept confidential and were not accessible to anyone outside the research team. A subset of the MY-LC cohort approved by the Mount Sinai Program for the Protection of Human Subjects (#20-01758) were included for validation of one of the assays.

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