Project DEFINE: Post-Vaccination Syndrome
Yale School of Medicine
AKIKO IWASAKI, PhD
Sterling Professor of Immunobiology and Professor of Dermatology and of Molecular, Cellular, and Developmental Biology and of Epidemiology (Microbial Diseases)
Study Objectives:
Define PVS clinically: Establish a working definition grounded in clinical, biological, and patient-reported data.
Deep phenotyping: Comprehensive functional, neurocognitive, sensory, and cardiac evaluation at a single visit.
Biological characterization: Detect circulating Spike protein, EBV reactivation, and immune dysregulation markers.
Trial readiness: Establish eligibility criteria and position participants for future therapeutic trials.
Background:
A small fraction of people who received COVID-19 vaccines have developed a persistent, debilitating condition known as Post-Vaccination Syndrome (PVS), also called PACVS. Despite credible self-reports and some early biological findings, PVS is not yet formally recognized as a clinical entity, and no validated diagnostic criteria or treatments exist. Most current knowledge rests on symptom surveys adapted from other chronic illnesses.
A key finding from the team's earlier LISTEN study was the detection of circulating Spike protein — both full-length and S1 subunit — in a subset of PVS participants for more than 700 days after exposure, including in individuals with no prior SARS-CoV-2 infection. This persistence of viral antigen is a central biological hypothesis driving DEFINE-PVS.
Study design:
Participants are drawn from the existing LISTEN-PVS cohort — specifically those with confirmed detectable Spike protein — and recruited from across the continental U.S. Each undergoes a single comprehensive in-person evaluation at a Trusted Medical clinical site, with biospecimens shipped to the Iwasaki laboratory at Yale for research assays.
Core Goals:
DEFINE-PVS is designed to establish a clinically grounded, biologically validated definition of PVS; identify distinguishing immune and functional patterns; generate eligibility criteria for future trials; and build the evidence base needed to inform clinical care and health policy — with participants treated as partners throughout.