Effectiveness and Impact of Maternal RSV Immunization and Nirsevimab on Medically Attended RSV in US Children.

Importance: During the 2024-2025 respiratory syncytial virus (RSV) season in the US, nirsevimab and maternal RSV vaccination became widely available to prevent severe RSV disease in infants. Assessments of the real-world effectiveness and impact of both products are needed to inform RSV prevention policy. Objectives: To estimate nirsevimab and maternal RSV vaccine effectiveness against medically attended RSV-associated acute respiratory illness (ARI) and to estimate the impact of these products on RSV-associated hospitalizations during 2024-2025. Design, Setting, and Participants: Population-based surveillance for medically attended ARI was conducted among children younger than 2 years with systematic molecular testing for RSV. Children were enrolled at 7 US pediatric medical centers from October 1, 2024, through April 30, 2025. A test-negative case-control design was used to estimate maternal RSV vaccine and nirsevimab effectiveness. Exposures: To estimate maternal RSV vaccine effectiveness, the exposure was maternal RSV vaccination among newborns and infants younger than 6 months at medical encounters; to estimate nirsevimab effectiveness, the exposure was nirsevimab receipt among newborns and infants younger than 8 months as of October 1, 2024, or born after that date. Main Outcomes and Measures: The primary outcome was medically attended RSV-associated ARI and RSV-associated hospitalization. Immunization effectiveness was calculated as (1 - adjusted odds ratio) × 100%. To estimate population-level impact of RSV prevention products, relative rate reductions were estimated by comparing observed RSV-associated hospitalization rates during 2024-2025 to (1) observed rates in 2017-2020 or (2) counterfactual 2024-2025 rates estimated by a difference-in-differences approach; estimates from both approaches are presented as ranges. Results: Overall, 5029 children younger than 2 years with medically attended ARI were enrolled during October 2024 to April 2025. Median (IQR) age was 10 months (5-16 months), and 2176 children (43.3%) were female. Among newborns and infants younger than 6 months, maternal RSV vaccine effectiveness was 64% (95% CI, 37%-79%) against any medically attended RSV-associated ARI and 70% (95% CI, 37%-86%) against RSV-associated hospitalization. Nirsevimab effectiveness was 81% (95% CI, 71%-87%) against RSV-associated hospitalization, and nirsevimab remained 77% (95% CI, 42%-92%) effective against RSV-associated hospitalization at 130 to 210 days after receipt. RSV-associated hospitalizations were reduced by 41% to 51% among newborns and infants aged 0 to 11 months, with the highest reduction of 56% to 63% in those aged 0 to 2 months. Conclusions and Relevance: According to the results of this population-based surveillance study, during 2024-2025, both maternal RSV vaccine and nirsevimab were estimated to be effective at protecting infants from RSV-associated hospitalizations in their first RSV season, and RSV-associated hospitalization rates in newborns and infants aged 0 to 11 months were reduced by up to half compared to seasons before these products were introduced.