RFA-IP-22-004, Evaluating respiratory virus vaccine effectiveness in a large, diverse healthcare system

Abstract - Component A We are applying for RFA components A and D. This abstract refers to Component A. Influenza/pneumonia comprise the 9th and COVID-19 the 3rd leading cause of death in the U.S., with the pandemic entering its 3rd year. Vaccine effectiveness (VE) estimates vary by host factors, viral clade, match to circulating virus, time since vaccination (i.e., waning) and specific vaccine characteristics. PittVax and collaborators have been integral to the US Flu VE Network for 12 years, contributing to influ- enza and COVID-19 VE estimates. Among the current 7 Network sites, PittVax ranks #2 in enrollments, #2 in bloodspot collections, and #1 in follow-up survey completion, while exceeding enrollment goals. PittVax has published >300 peer-reviewed articles in the field. We propose a test-negative case-control design (TND) study among UPMC and federally qualified health center (FQHC) outpatients to determine influenza, COVID-19 and possibly, other respiratory virus VE. Our specific aims are: 1) Determine VE against laboratory-confirmed, medically-attended, acute respiratory in- fections among 1000-1200 outpatients during the influenza season in age groups: 6 mos-18 yrs, 19-49 yrs, and ≥50 yrs, using test negative design in onsite enrollment during respiratory season plus remote enroll- ment outside of influenza season (another 400-900 if COVID-19 persists); 2) provide genetic sequencing on selected specimens for biweekly trends in clade; and 3) determine the annual, population-based burden of influenza and COVID-19 for Allegheny County (Pittsburgh) from the UPMC Health Plan. For determining prior infection for SARS-CoV-2 (e.g., N protein) in the highest proportion of participants, we propose finger- stick bloodspots, supplemented by sera on a subset, for more in-depth studies. The Williams lab, using vali- dated 96-well plate instruments for RT-PCR, which analyzed >10,000 specimens over the last 6 years for influenza, SARS-CoV-2 and other respiratory viruses, will determine presence of infecting viruses. The ex- perienced Harrison lab will perform viral genomic sequencing. We will obtain immunization records from the state's registry and from UPMC's and the FQHC's electronic records. UPMC Health Plan is the largest insurer in Allegheny County and at UPMC in 2021-22, >126,000 county residents were clinically tested for SARS-CoV-2. Annually, UPMC records >5.6 million outpatient visits. Over 1.4 million UPMC acute care visits a year are assessed at Emergency Departments (EDs) and Urgent Care clinics through a common structure and e-record with 305,751 ED visits in 2021 among our four recruiting EDs. UPMC has been rated one of the most wired health systems for 23 years. To address health equity, we add FQHC offices serving mostly persons of color and leadership from the Black Equity Coalition to our multidisciplinary team to assist with culturally competent script/survey development, inclusion of social deter- minants of health data and dissemination of findings with a health equity perspective.