Impact of a Universal Nirsevimab Prevention Program Against Respiratory Syncytial Virus Bronchiolitis in Infants in Sicily (Italy) During the 2024–2025 Epidemic Season: A Retrospective Cohort Study

<b>Objectives</b>: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024-2025 season. This study assessed the real-world impact of this strategy in reducing RSV-related hospitalizations. <b>Methods</b>: This retrospective cohort study examined newborns residing in Sicily from 2015 to May 2025, evaluating hospitalization incidence rates attributable to RSV during the first year of life. RSV hospitalizations were identified using ICD-9 codes (079.6, 466.11, 480.1) in any diagnostic position. Incidence rates in the 2024-2025 season (intervention period) were compared with preceding seasons. <b>Results</b>: During the study period, 4431 RSV hospitalization cases occurred (19.84 cases per 1000 person-years), peaking in 2023-2024 (53.47 cases per 1000 person-years). A statistically significant 40% reduction in RSV hospitalizations was observed during the 2024-2025 season (October-April) compared with the preceding season, with a relative reduction ranging between 33.4% and 54.8% across sensitivity models. <b>Conclusions</b>: These results confirm the significant impact of the universal prophylaxis program in real-world practice, consistent with other European programs. These findings support universal RSV prevention strategies and provide insights for optimizing regional and national health policies.