Effectiveness of a targeted infant RSV immunization strategy (2024-2025): A multicenter matched case-control study in a high-surveillance setting

Background: Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced to prevent infant RSV-related hospitalizations. Although efficacy has been demonstrated in clinical trials, real-world data on targeted immunization strategies remain limited. We aimed to evaluate the effectiveness of nirsevimab in preventing RSV-associated hospitalizations in infants under 12 months, within a seasonal program prioritizing infants born from April onwards. Methods: We conducted a prospective, multicenter, matched case-control study across seven Italian hospitals during the 2024–2025 RSV season. Infants hospitalized with PCR-confirmed RSV bronchiolitis were matched 1:2 by age and date of admission to controls hospitalized for non-respiratory causes. Data were collected via electronic medical records. Immunization effectiveness (IE) was estimated using conditional logistic regression adjusted for sex assigned at birth, gestational age, birth weight, and clinical risk factors. Two pre-specified stratified analyses and a sensitivity analysis using inverse probability of treatment weighting (IPTW) were performed. Results: A total of 138 infants were included (46 cases, 92 controls). Adjusted IE was 89.5% (95% CI: 60.3–97.2%). Stratified analyses yielded similar results among infants born after April 1 (IE: 88.4%, 95% CI: 56.5–96.9%) and those without risk factors (IE: 88.1%, 95% CI: 45.7–97.4%). IPTW analysis confirmed protection (IE: 79.6%, 95% CI: 53.5–91.0%). Conclusions: This study provides real-world evidence supporting the effectiveness of nirsevimab in a targeted seasonal immunization framework. These findings may inform phased implementation strategies and RSV prophylaxis policies in varied healthcare settings.