RFA-IP-22-004, Michigan-Ford Initiative to Measure Vaccine Effectiveness (MFIVE): Seasonal Influenza, COVID-19 and Respiratory Virus Vaccines

Component A: Michigan-Ford Initiative to Measure Vaccine Effectiveness (MFIVE): Seasonal Influenza, COVID-19, and Respiratory Virus Vaccines The use of active surveillance for medically-attended acute respiratory illness (MAARI) in outpatient settings has been the cornerstone of vaccine effectiveness (VE)

monitoring in the U.S. for over a decade. As a part of the U.S. Flu VE Network for 10-years, the Michigan Center for Respiratory Virus Research and Response has the expertise and the infrastructure to build upon the findings of previous test-negative studies to support real-time VE assessments for SARS-CoV-2 and influenza

vaccines. Our primary goal is to build upon our previous efforts to evaluate the effectiveness of vaccines against SARS-CoV-2 and influenza in prevention of MAARI. We will conduct VE surveillance throughout Southeastern Michigan through recruitment of patients presenting at ambulatory clinics and testing centers

spanning two healthcare systems. Our enrollment sites are distributed throughout multiple communities in the region, including clinics serving populations disproportionately impacted by infectious diseases. This study will integrate analyses of antibodies, whole genome sequences of viruses, and detection of non-influenza, non-

SARS-CoV-2 respiratory viruses (e.g. RSV). We will use these evaluations to expand upon the test-negative methodology to provide a more accurate and robust assessment of VE. Our specific objectives are as follows: Objective 1. Determine vaccine effectiveness of influenza and COVID-19 vaccines in children and adults from

ambulatory settings. We will do this through active enrollment of individuals with MAARI, collection and testing of respiratory specimens, and verification of health data and vaccination history. Objective 2. Conduct viral genomic sequencing of influenza and SARS-CoV-2 for surveillance and to support

variant and clade-specific estimates of VE. We will leverage our existing, robust sequencing pipeline to provide timely sequencing data from both research and clinically-collected respiratory specimens. Objective 3. Efficiently maintain SARS-CoV-2 surveillance and COVID-19 vaccine effectiveness evaluations

among ambulatory patients during periods when influenza viruses are not circulating. We will accomplish this through standardized queries of the electronic medical records of our two participating major medical centers, with regular integration with state vaccination registry data. Our primary outcome will be rapid determinations of

vaccine effectiveness, through regular deliveries to CDC to support vaccine recommendations for the general population and to inform selection and development of future vaccines.