First- and Second-Year Outcomes After Nirsevimab Immunization

The consistency of nirsevimab effectiveness across consecutive seasons and its broader clinical protective effects remain to be fully characterized.

To assess whether first-season effectiveness of nirsevimab against respiratory syncytial virus (RSV)-lower respiratory tract infection (LRTI)-related hospitalizations is maintained during a new RSV season, whether the effectiveness persists beyond the first season, and whether nirsevimab exposure is associated with hospitalizations for non-RSV infections and asthma during the first and second years of follow-up.

This cohort study analyzed 2 nationwide matched cohorts using the French National Health Data System, including infants born in metropolitan France before the 2023 and 2024 immunization campaigns. Infants receiving nirsevimab were matched 1:1 to unimmunized infants. Both cohorts were followed up for 1 year after immunization, with an additional second year of follow-up for the 2023 cohort. Data analysis was performed from February 2023 to August 2025.

Single dose of nirsevimab.

RSV-LRTI-related, non-RSV infection, and asthma hospitalizations were assessed using weighted Cox proportional hazards models.

This cohort study included 74 672 infants in 2023 and 175 526 in 2024. At baseline, the mean (SD) age of immunized infants was 4.5 (2.0) months in the 2023 cohort; 19 633 (52.6%) were male and 17 703 (47.4%) were female. The mean (SD) age of the 2024 cohort was 4.8 (2.2) months; 44 863 immunized infants (51.1%) were male and 42 900 (48.9%) were female. Among 37 366 infant pairs in 2023 and 87 763 pairs in 2024, RSV-LRTI-related hospitalizations during the first year of follow-up occurred in 299 (0.8%) immunized vs 899 (2.4%) unimmunized infants in 2023 and 456 (0.5%) vs 1711 (1.9%), respectively, in 2024. Nirsevimab was associated with a lower rate of RSV-LRTI-related hospitalization in both the 2023 and 2024 cohort during the first year of follow-up, with effectiveness estimates of 66% (95% CI, 61%-70%) and 72% (95% CI, 69%-75%), respectively. An association with higher rates of hospitalization for ear, nose, and throat (ENT) bacterial infections was observed (2023 cohort: weighted hazard ratio [wHR], 1.36; 95% CI, 1.00-1.84; 2024 cohort: wHR, 1.43; 95% CI, 1.15-1.78). No significant association was observed for other outcomes. During the second year of follow-up, no protective association was observed for RSV-LRTI-related hospitalization (wHR, 1.03; 95% CI, 0.73-1.43). An association with higher rates of hospitalization for ENT (wHR, 1.56; 95% CI, 1.10-2.22) and asthma (wHR, 1.24; 95% CI, 1.05-1.46) was observed.

This study found that nirsevimab was associated with a substantial reduction in RSV-LRTI-related hospitalizations during the first year across both the 2023-2024 and 2024-2025 seasons. It was not associated with reduced hospitalizations due to non-RSV infections or asthma, nor during the second year of follow-up.