Bivalent RSVpreF effectiveness against RSV-associated hospital or emergency department care over two seasons: a retrospective test-negative case control study

Background: Since RSV vaccine licensure in 2023, vaccine effectiveness (VE) studies demonstrated first season protection against severe RSV disease including RSV-related hospitalization/emergency department (ED) visits. Here, we estimate VE over two seasons, by RSV subtype, and for additional high-risk subgroups. Methods: This retrospective test-negative case-control study included adults ≥60 years at Kaiser Permanente Southern California with lower respiratory tract disease (LRTD) or acute respiratory illness (ARI) hospitalization/ED during 24 November 2023─09 April 2024 and 05 November 2024─26 April 2025. In primary analyses, cases were RSV-positive and controls were negative for: RSV, SARS-CoV-2, influenza, and positive for a non-vaccine-preventable pathogen. Exposure was bivalent RSVpreF receipt ≥21 days before LRTD/ARI. VE was calculated using adjusted odds ratios from multivariable logistic regression. "First season after vaccination" includes events in the same RSV season as vaccination; "second season" includes events in 2024-25 among those vaccinated in 2023-24. Findings: VE against RSV-associated LRTD hospitalizations/ED was 81% (95% CI: 68-89) and 76% (95% CI: 48-89) for first and second seasons after vaccination, respectively. Limiting to those vaccinated in 2023/2024, VE was 87% (95% CI: 37-97) 0-