Observational epidemiology for evaluating respiratory virus vaccine impact using population surveillance data

Observational studies of vaccine preventable diseases (VPDs) are needed to answer questions not addressed by clinical trials and inform policy decisions. In addition, data from community, rather than clinical, settings are essential as clinical surveillance largely does not capture individuals at low risk for severe disease and may not be representative of subclinical disease. Also, mild illness can contribute to onward community transmission and result in missed work or school. Such observational data from community settings is needed both for diseases with licensed vaccines in routine use and diseases with vaccines in clinical development that are expected to be licensed. This dissertation aims to address two epidemiologic gaps for respiratory viruses: (1) estimating effectiveness of COVID-19 booster vaccination among healthy, young adult populations and (2) describing genomic diversity of respiratory syncytial virus (RSV) to inform future vaccine impact studies. In Chapter 1, we provide a rationale for the use of observational epidemiology in the study of VPDs and provide a brief introduction of the specific aims of this dissertation. In Chapter 2, we used data from the Husky Coronavirus Testing Study (HCT), a large SARS-CoV-2 university testing program, to estimate relative vaccine effectiveness (VE) of COVID-19 mRNA vaccine primary series plus monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection. Data are from September 2021 to July 2022 in a community-based university population. Relative VE was estimated using the test-negative design and adjusted logistic regression implemented via generalized estimating equations (GEE). Analyses included 2,218 test-positive cases (59% received monovalent booster dose) and 9,615 test-negative controls (62%) from 9,066 individuals, with median age of 21 years. Estimated adjusted relative VE of primary series plus monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40% (95% CI: 33–47%) during the overall analysis period and 46% (39–52%) during a period of Omicron circulation. In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection. In Chapter 3, we used data from the Seattle Flu Study (SFS), a community-based respiratory virus surveillance study in Seattle, USA and publicly available RSV genomes to assess genomic diversity of RSV over four respiratory virus seasons (2019–2020, 2020–2021, 2021–2022, and 2022–2023). SFS nasal swabs were collected and tested for RSV by RT-qPCR, with whole genome sequencing (WGS) performed for a subset. Among SFS samples collected from children and adults, 1.8% (232/13014) and 0.2% (86/46042) respectively tested positive for RSV-A and 1.1% (139/13016) and 0.3% (119/46043) for RSV-B. In Washington, USA during 2019–2020, RSV-A and RSV-B co-circulated (majority clades A.D.1 and B.D.4.1.1). No RSV was observed in 2020–2021 following implementation of nonpharmaceutical interventions to reduce SARS-CoV-2 transmission. Subsequently, RSV re-emerged off-season in 2021–2022 and shifted to mostly RSV-B (clade B.D.E.1) and then RSV-A (clade A.D.5.2) in 2022–2023. Shifts in genomic diversity over time were similar for all ages. We used community-based respiratory virus surveillance data from two studies to answer questions regarding two VPDs, COVID-19 and RSV. Results may inform the evidence base for policy recommendations for COVID-19 and RSV vaccines as well as provide a comparison for future monitoring of SARS-CoV-2 and RSV using similar surveillance data.