Effectiveness of nirsevimab against hospitalisation for RSV-bronchiolitis during high RSV-B circulation in the second year of nationwide implementation in France: a test-negative case-control study.

Background: Nirsevimab was first introduced in September 2023, showing strong real-world effectiveness in preventing hospitalised RSV-bronchiolitis. RSV-A circulation predominated during 2023-2024, whereas RSV-B was frequent in 2024-2025. Recent reports indicated resistance to nirsevimab in RSV-B strains in France. We aimed to assess the effectiveness of large-scale nirsevimab implementation against hospitalised RSV-bronchiolitis during high RSV-B circulation. Methods: A test-negative case-control study was conducted using a national hospital-based surveillance system. All children <12 months hospitalised for bronchiolitis and tested for RSV in 12 French hospitals from October 10, 2024 to March 15, 2025, were included. Cases were RSV-positive bronchiolitis; controls were RSV-negative bronchiolitis. Effectiveness was assessed by a multivariable logistic regression model adjusted for confounders (sex, gestational age at birth, birth weight, risk factors for severe bronchiolitis, month of diagnosis, and medical centre). A range of sensitivity analyses was conducted. Findings: 1270 patients were included; among which 830 (65.3%) were RSV-positive and 440 (34.7%) were RSV-negative bronchiolitis. The male-to-female sex ratio was 1.35, and the median age was 3 months (IQR: 1.5-5.6). Among cases, 182 (22.0%) received nirsevimab, compared to 282 (64.1%) for controls. Adjusted effectiveness against RSV-bronchiolitis was 84.9% (95% CI, 80.0-88.6). Subgroup analyses by age and severity (intensive care unit admission, respiratory support) showed consistent results, along with sensitivity analyses. Interpretation: Despite high RSV-B circulation, which has recently been identified to carry mutations potentially inducing resistance to nirsevimab, the effectiveness of the second national nirsevimab campaign against hospitalisation for RSV-bronchiolitis remained high. Funding: The study received financial support from Sanofi, AstraZeneca, and the 2023 ATIP-Avenir grant from the National Institute of Health and Medical Research (Inserm).