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.