Highlight
– A multicenter test‑negative case‑control study of 636 infants in France showed high effectiveness of a single dose of nirsevimab against RSV bronchiolitis in pediatric emergency departments across two consecutive seasons (83.2% and 89.3%).
– Effect estimates were consistent between seasons (P = .97) despite reports of newly observed RSV‑B mutations during the first implementation year.
– Results support continued use of nirsevimab for broad infant protection, but ongoing genomic and epidemiologic surveillance remain essential.
Background — disease burden and therapeutic context
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in infants and young children worldwide, driving large numbers of emergency department visits and hospitalizations during seasonal epidemics. Severe RSV in early infancy can require supportive respiratory care and is associated with short‑term morbidity and health‑care utilization and, in some cases, intensive care.
Until recently, passive immunoprophylaxis for RSV in infants was limited to palivizumab, reserved for very high‑risk infants due to cost and dosing constraints. Nirsevimab (MEDI8897) is a long‑acting monoclonal antibody targeting the prefusion F protein of RSV that provides passive immunity with a single dose and has been implemented in several national immunization programs as a broader preventive measure for infants. As with any targeted biologic, viral evolution (notably in the F protein) raises questions about potential resistant variants and the durability of clinical effectiveness.
Study design and methods
The study by Lenglart et al. (JAMA Network Open, 2025) was a multicenter test‑negative case‑control study conducted in five pediatric emergency departments in France over the first two seasons after national implementation of nirsevimab (season 1: Oct 5, 2023–Feb 29, 2024; season 2: Oct 15, 2024–Jan 31, 2025).
Eligible participants were infants younger than 1 year presenting with a first episode of bronchiolitis who underwent nasopharyngeal testing for RSV. The primary outcome was RSV test positivity among bronchiolitis cases. The investigators used multivariable logistic regression with nirsevimab status as the primary exposure, adjusted for potential confounders including age, sex, presence of bronchiolitis risk factors, type of childcare, month of presentation, and center.
Effectiveness was derived from adjusted odds ratios (1 − adjusted OR) and presented separately for each season, with a likelihood ratio test used to compare season‑specific estimates. Additional prespecified subgroup analyses (by age and disease severity) and sensitivity analyses were performed to assess robustness.
Key findings
The study enrolled 636 infants with bronchiolitis (median age 3.0 months; interquartile range 1.4–5.0 months; 333 boys [52.4%]). Overall, 162 of 636 infants (25.5%) had received nirsevimab prior to their bronchiolitis episode.
RSV detection rates among bronchiolitis cases were similar across seasons: 273 of 384 (71.1%) in season 1 and 181 of 252 (71.8%) in season 2.
Adjusted effectiveness estimates of nirsevimab against RSV bronchiolitis were strong in both seasons: 83.2% (95% CI, 68.0%–91.4%) in the first season and 89.3% (95% CI, 77.8%–95.1%) in the second season. The statistical comparison indicated no significant difference between seasons (P = .97). Subgroup analyses by age and severity and multiple sensitivity analyses produced similar point estimates, supporting the robustness of findings.
Importantly, these results were observed against the backdrop of surveillance reports that identified new RSV‑B mutations during the first implementation year. In this cohort, those genomic observations did not translate into a measurable reduction in nirsevimab effectiveness at the population level within pediatric emergency settings.
Expert commentary and interpretation
These findings provide timely, real‑world evidence that a single dose of nirsevimab confers substantial protection against RSV bronchiolitis leading to pediatric emergency care in the first year of life. The test‑negative design, commonly used for vaccine effectiveness studies, is well suited for respiratory pathogens where symptomatic testing is routine and helps mitigate biases related to health‑care seeking behavior.
The high and sustained effectiveness across two seasons is reassuring given concerns about viral evolution. While the detection of RSV‑B mutations warrants molecular vigilance, the lack of an observed clinical impact in this study suggests that those mutations either do not substantially alter the nirsevimab epitope or that the polyclonal pressure at the population level has not yet yielded functionally resistant strains in numbers sufficient to affect outcomes.
Study strengths
– Multicenter real‑world design across consecutive seasons provides practical effectiveness estimates complementary to clinical trial efficacy data.
– Use of a test‑negative approach reduces bias from differential care seeking and testing practices.
– Adjustment for key confounders and consistent findings across sensitivity and subgroup analyses strengthen causal inference.
Limitations and caveats
– The population was restricted to infants presenting to pediatric emergency departments with first bronchiolitis episodes; results may not generalize to primary care settings, asymptomatic infections, or older infants and children.
– The study reports effectiveness against RSV detection among bronchiolitis cases, not directly against hospitalization, intensive care admission, long‑term outcomes, or mortality. Although reductions in ED presentations likely signal reduced severe disease at a population level, more granular severity and resource‑use data would be useful.
– Sample size, while adequate for the primary comparisons, is modest for rare outcomes such as vaccine escape or variant‑specific failure; ongoing surveillance with integration of viral genomic sequencing will be required to detect and characterize emerging resistance.
– The observational design cannot completely eliminate residual confounding despite multivariable adjustment; for example, differences in timing of prophylaxis, health‑seeking behavior, or unmeasured socioeconomic variables might influence estimates.
Clinical and policy implications
The high effectiveness of nirsevimab in preventing RSV‑positive bronchiolitis presentations supports its role as a broad prophylactic strategy to reduce infant RSV disease burden and emergency department pressure during seasonal epidemics. For clinicians, the data provide reassurance that, at least in the short term and at the population level, emergent RSV‑B mutations have not eroded clinical protection.
For policymakers and immunization programs, these findings favor continued or expanded incorporation of nirsevimab into infant RSV prevention strategies, while recognizing that cost, delivery logistics, and equity considerations remain central to implementation decisions.
Research and surveillance priorities
– Continued active surveillance that pairs clinical outcomes with viral genomic data is essential to identify and characterize any emergent escape variants early.
– Studies that assess effectiveness against severe endpoints (hospitalization, ICU admission), longer follow‑up, and varied health‑care settings will improve generalizability and health‑economic modeling.
– Comparative effectiveness assessments versus targeted prophylaxis (e.g., palivizumab for high‑risk infants) and cost‑effectiveness analyses across health systems are needed to guide resource allocation.
– Basic and translational research to map epitope changes and neutralization escape thresholds will help predict the functional impact of observed mutations and inform potential next‑generation monoclonal antibody design.
Conclusion
In this multicenter test‑negative case‑control study from France, nirsevimab provided high and consistent effectiveness against RSV bronchiolitis among infants presenting to pediatric emergency departments across the first two seasons after implementation (83.2% and 89.3%). Despite the detection of RSV‑B mutations during early rollout, no clinically meaningful loss of protection was observed. These real‑world data support continued programmatic use of nirsevimab for infant RSV prevention, coupled with robust genomic and epidemiologic surveillance to promptly detect and respond to any future resistance signals.
Funding and trial registration
Funding and trial registration details are reported in the original publication (Lenglart et al., JAMA Netw Open 2025). Readers should consult the source article for complete disclosures and funding statements.
References
1. Lenglart L, Levy C, Basmaci R, et al. Nirsevimab Treatment of RSV Bronchiolitis in Pediatric Emergency Departments. JAMA Netw Open. 2025;8(10):e2540720. doi:10.1001/jamanetworkopen.2025.40720
2. Centers for Disease Control and Prevention. Respiratory Syncytial Virus (RSV) — Clinical Features. CDC. https://www.cdc.gov/rsv/index.html. Accessed November 2025.
3. World Health Organization. Respiratory syncytial virus (RSV). WHO. https://www.who.int/news-room/fact-sheets/detail/respiratory-syncytial-virus-(rsv). Accessed November 2025.
AI thumbnail image prompt
Photorealistic image of a concerned young infant wrapped in a hospital blanket sitting on an exam table in a pediatric emergency department; a clinician in scrubs and gloves gently examining the infant while holding a syringe‑symbolic icon representing a monoclonal antibody; faint overlay of stylized RSV viral particles in the background and a simple hospital setting, cool clinical color palette, high resolution.