Impact of Universal Nirsevimab Immunoprophylaxis on RSV-Related Hospitalizations in Infants: A Two-Season Multicenter Study in Northern Italy

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization in infants worldwide. In 2024, the Piedmont region introduced universal immunoprophylaxis with Nirsevimab for all infants experiencing their first RSV season. We carried out a multicenter retrospective observational study across the three pediatric units of ASL TO4 (Ivrea, Ciriè, Chivasso), comparing bronchiolitis-related hospitalizations during the 2023–2024 season (pre-Nirsevimab) with those from the 2024–2025 season (post-Nirsevimab). The primary outcome was the proportion of RSV-positive hospitalizations. Secondary outcomes included age at admission, need for respiratory support, PICU/NICU transfer, and length of stay. Immunization coverage was assessed using the regional electronic registry. Immunization coverage exceeded 88% across all centers (overall 90.4%). A total of 179 bronchiolitis hospitalizations were recorded (134 pre- vs. 45 post-Nirsevimab). RSV-positive admissions showed a reduction from 70.9% to 55.6% after implementation (OR 0.52; 95% CI 0.24–1.09). Center-specific analyses suggested reductions in Ciriè (OR 2.48; 95% CI 1.41–4.39) and Chivasso (OR 2.28; 95% CI 1.09–4.77), with a similar trend observed in Ivrea. In a supplementary denominator-based analysis restricted to infants younger than 12 months, RSV-related hospitalization incidence decreased from 42.0 to 10.3 per 1000 infants between seasons (OR 4.23; 95% CI 2.64–6.78; p < 0.0001). Disease severity remained unchanged between seasons in terms of respiratory support, length of stay, and PICU/NICU transfers. Age at admission increased significantly during the post-intervention season (mean 118.3 vs. 160.9 days; Welch’s two-sample t-test, p = 0.026). Among 15 immunized infants hospitalized in 2024–2025, 6 were RSV-positive, none required intensive care, and only two needed high-flow nasal cannula (HFNC). Universal Nirsevimab prophylaxis was associated with a trend toward reduction in RSV-related hospitalizations at the aggregate level, although the overall comparison did not reach statistical significance. Center-specific analyses suggested reductions in RSV-positive admissions in some participating units. A supplementary denominator-based analysis among infants younger than 12 months showed a lower incidence of RSV-related hospitalizations during the post-implementation season. No evidence of increased severity among breakthrough cases was observed. High coverage demonstrated the feasibility of implementation and its potential public health value. Continued longitudinal surveillance over additional RSV seasons is essential to better define the durability of protection and long-term epidemiological impact.