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.