PROJECT 1 SUMMARY The rapid spread COVID-19 and its extreme range of pathologies creates an urgent need to understand transmission and levels of protection following SARS-CoV-2 infection. These issues are most effectively studied in cohorts with individuals at high risk of exposure and, critically, their most frequent contacts. Project 1 will answer pressing questions about COVID-19 transmission and protection in such a group, Columbus, OH first responders and their household contacts. Longitudinal serology and virus testing will be performed over the next five years by the Project 1 team to determine COVID-19 prevalence, transmission, and protection in this cohort. An inherent feature of the research plan is its flexibility, also allowing us to pivot serological/viral tracking when vaccines are available, which, likely, will be deployed in a first stage to this high-risk cohort. We will employ a panel of serological and genetic assays, developed or validated at our institution, to address key knowledge gaps about COVID-19, including: (i) prevalence among a high-risk exposure group, (ii) causal relationships with PPE practices, (iii) transmission among household contacts, (iii) viral load and whether positive PCR results equate with infectious virus, (iv) evolution and durability of Ab responses to natural infection and re-infection over a range of symptoms, (v) humoral immune responses post-vaccination in naïve and previously infected individuals, and (vi) protection from re-infection or infection post-vaccination. Importantly, Project 1 studies will benefit from an OSU commitment to fund our proposed clinical testing. The project also will benefit from integration of transdisciplinary experts from emergency medicine, immunology, virology, pathology, infectious disease, epidemiology, biostatistics, and bioethics, as well as partnerships with local/state agencies. Project 1 will be accomplished in two Aims. AIM 1. Enhance existing infrastructure to longitudinally sample a cohort of first responders, staff, and household contacts. We have established a high buy-in rate for participation of this high-exposure risk group in the Columbus area (anticipated lower limit recruitment of ~2,500). AIM 2. Determine duration and protectiveness of antibody responses in STOP-COVID participants. We expect to enlist a broad spectrum of participants who, during the study, will include naïve, previously exposed, asymptomatic, and symptomatic individuals. We will leverage longitudinal serologic data to track all categories of exposed individuals for the magnitude, duration, neutralizing capacity, and protectiveness of antibody responses. When a vaccine is available, participants will provide a closely tracked cohort of priority recipients to monitor humoral immune responses to the vaccine in naïve and previously exposed individuals at a high risk for re-exposure. These studies will synergize with: Project 2 for an in-depth characterization of the immune responses ...