Project Summary/Abstract This project expands the GenX Exposure Study funded through the NC State Center for Environmental and Health Effects of PFAS to answer urgent questions related to per-and polyfluoroalkyl substances (PFAS) exposure and their impacts on SARS-CoV-2 response. PFAS as a class are associated with immune suppression as evidenced in humans by lower antibody titers to common vaccines in higher exposed individuals. Using the GenX Exposure Study, a prospective study of 1,000 PFAS exposed individuals, we plan to answer two questions: 1) what is the prevalence of overt disease, symptoms, sequelae, and antibodies in this population? and 2) does PFAS exposure modify response to virus as measured by antibodies? This study, located in the Cape Fear Region of North Carolina, includes participants ranging in age from 8-86 years with diverse demographic and medical histories. PFAS levels in this study are much higher than the national values for PFAS measured; in this population, novel fluoroethers have been measured in serum and represent ~25% of the overall PFAS levels in serum. In this population, we plan to collect two blood samples for SARS-CoV-2 antibody testing, once in the fall of 2020 and again in the summer of 2021. Additionally, we will administer a survey related to COVID 19 disease and symptoms at five points in time during this one-year study to capture the ongoing disease experience of the cohort. We currently anticipate a prevalence of antibody positive infection of 10% (June 2020); we expect this to increase as the rates of infection are increasing in North Carolina. We will use PFAS values measured in Fall 2020 to assess the impact of PFAS exposure and SARS-CoV-2 response in cross-sectional analyses; we will use the same PFAS measures to assess PFAS exposures on these outcomes in a longitudinal fashion for data collected following PFAS measurement. With 1000 participants, this will be one of the largest studies to date regarding PFAS exposure and immune response as measured by antibodies. Given that PFAS suppress immune function, exposure may result in worse disease because individuals fail to make sufficient antibodies to the virus, or may result in milder disease since the so-called “cytokine storm” may be mitigated by poorer immune response. Our study will provide the survey data combined with antibody data and stored specimens to further explore how PFAS influence COVID. If a vaccine becomes available and is adopted during our study, we will shift our focus to vaccine response. We plan to work with our community partners both local non-governmental organizations and health departments to share results with study participants and the community in a timely fashion. This supplement complements the ongoing research at the NC State Superfund Center and allows us to leverage an ongoing epidemiological study to address this important public health issue.