Real-world impact of nirsevimab on the epidemiology and severity of pediatric respiratory syncytial virus infections: a three-season cohort study in Italy.

To evaluate the real-world impact of universal nirsevimab prophylaxis on the proportion of positive tests, seasonality, and severity of pediatric respiratory syncytial virus (RSV) infections and to explore the associated changes in respiratory virus seasonality. This is a retrospective, cohort study held in a single pediatric emergency department in a tertiary care hospital in Italy. We evaluated 758 children under 18 years of age presenting with respiratory symptoms who underwent multiplex PCR testing during three consecutive respiratory seasons (1 October to 30 April) from 2022 to 2025. Universal nirsevimab prophylaxis was implemented for infants in their first RSV season was broadly introduced in the 2024-2025 season starting November 1, 2024. Outcomes were compared between the pre-nirsevimab era (2022-2024) and the nirsevimab era (2024-2025). The primary outcome was the seasonal RSV positivity rate. Secondary outcomes included rates of hospitalisation, length of stay (LOS), requirement for respiratory support, and intensive care unit (ICU) admission. The proportion of RSV-positive tests decreased from a mean of 31.9% in the two pre-nirsevimab seasons to an overall 19.7% in the nirsevimab season. In infants aged 0-12 months, the rate fell from a mean of 45.4% to 19.9%. Among RSV-positive infants (0-12 months) in the 2024-2025 season, those who received nirsevimab (n = 12) had a shorter median hospital LOS (6.0 vs 8.5 days) and a lower requirement for high-level respiratory support (25.0% [3/12] vs 58.3% [14/24]) compared to unprotected infants (n = 24).

conclusionsThe introduction of a universal nirsevimab programme was associated with a substantial reduction in RSV positivity and the burden of severe disease. In this real-world setting, nirsevimab appeared to mitigate severe outcomes even in infants with breakthrough infections. WHAT IS KNOWN: • Nirsevimab has demonstrated high efficacy in randomized controlled trials; however, real-world evidence regarding its impact onpopulation-level RSV positivity remains limited. • There is a paucity of data concerning the clinical characteristics and healthcare resource utilization associated with breakthrough infections following nirsevimab administration. WHAT IS NEW: • Implementation of a universal program was associated with a significant decrease in RSV positivity and markedly milder breakthrough infections, characterized by shorter hospital stays and reduced need for respiratory support. • Protection was consistently observed across the 0-12 and 0-6 month cohorts, supporting the role of nirsevimab in mitigating severe disease and justifying its broad implementation to alleviate healthcare system burden.