Abstract University Hospitals of Cleveland (UHC) proposes to join the US Platform Measuring Effectiveness of Seasonal Influenza, COVID-19 and other Respiratory Virus Vaccines for the Prevention of Acute Illness in Ambulatory Settings with its project CORVETS - Cleveland Ohio Respiratory Viruses Vaccines Effectiveness across Traditional Risk Factors and Social Determinants of Health. This application is in partnership with Case Western Reserve University and the Louis Stokes Cleveland VA Medical Center and includes Components A, C, D and E. Through this partnership, the study team will be able to recruit from a racially diverse source population and have access to innovative testing technologies. The aims for Component A are to enroll and establish an electronic repository on at least 1,000 patients annually with medically attended acute respiratory viral illness (RVI) in the ambulatory setting throughout the study period to measure the effectiveness of respiratory virus vaccines in children and adults on laboratory ascertained medically attended acute respiratory illness presenting to an ambulatory setting. The study team will establish and implement a comprehensive molecular diagnostic platform including viral genomic sequencing of patients experiencing respiratory illness for underlying RVIs associated with influenza (IFV) and COVID-19 to detect and catalog viral variants. The aim for Component C is to identify individual level and household-level factors that contribute to household transmission of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) and determine the effectiveness of vaccination and antiviral treatment in preventing household transmission of SARS-CoV-2 and influenza. To accomplish this aim, we will conduct a case-ascertained household transmission study to identify individual-level and household-level factors associated with transmission. Component D is a sample acquisition arm of the consortium that will obtain pre- and post-vaccination samples for immunologic study by the study consortium’s designated laboratory. These samples can be used to compare the immune responses measured in this component in the various subject groups with the with the clinical observations noted in the Component A arm of the study on clinical vaccine effectiveness. The component C activities aim to recruit and enroll 150 to 200 subjects who are eligible to receive specific influenza and COVID-19 vaccines and obtain samples pre- and post-vaccination in addition to a comprehensive and detailed history of prior vaccines, prior respiratory illness, past medical history, and current medications. Component D studies enable us to gain a better understanding of how vaccines work in vulnerable populations such as children and the elderly as well as in subjects receiving a variety of different vaccination products and schedules. The aims of Component E are to characterize and understand individual and population differences in immune response to ...