This project would establish and sustain a national longitudinal cohort of repeat blood donors with the purpose of monitoring changes in antibody titers against common or novel respiratory viruses; surveying the donors to assess for risk factors for infection, vaccination status, respiratory symptoms,

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and severe illness; and establishing a repository for further analysis as new assays to measure the immune response to respiratory virus infections are developed.During the COVID-19 pandemic, CDC used a contract mechanism to fund national serosurveillance studies, which used regular antibody assessments and surveys to monitor the burden of infection, risk factors for infection, and explore the duration and extend of immunity by population throughout the US (2020-2022).

By 2022, algorithms for using quantitative antibody titers to detect reinfection were established and tested, creating novel systems for monitoring burden even in the setting of high overall seroprevalence.Adapting these tools to the current context, this research cooperative agreement would establish a large-scale longitudinal cohort (>50,000 persons) of repeat blood donors with the purpose of:
1) estimating the national burden of incident SARS-CoV-2 infection, and further adapting the approach to other respiratory viruses as technology allows including Respiratory Syncytial Virus, Influenza, Human Metapneumovirus, EVD-68, and others; 2) determining antibody thresholds for protection across multiple respiratory viruses; 3) assessing state- or region-specific population-level immunity to/risk for infection through tracking median antibody titers within various populations; and 4) monitoring waning immunity and changes in immune capabilities in the context of ongoing viral evolution.