Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in children, but most burden estimates come from hospital settings. The RSVComNet ITA network previously reported clinical presentation and hospitalization risk for RSV in primary care across four Italian seasons (2019‑20, 2021‑22, 2022‑23, and 2023‑24). Here, we extend our analysis to include the 2024‑25 season. METHODS: We conducted a prospective, multicenter cohort study across five Italian regions, enrolling children under 5 years old presenting to primary care pediatricians who met the WHO-ARI criteria. At enrollment, nasopharyngeal swabs were tested by multiplex RT‑PCR for RSV and other respiratory pathogens. RSV‑positive children underwent follow‑up at 14 and 30 days. Primary outcomes included illness duration, symptom persistence, RSV-attributable hospitalization rate, and length of stay. We used an elastic-net logistic model (α tuned via 10-fold cross-validation, λ selected to maximize the AUC) to derive age-specific hospitalization risk with bootstrap-estimated 95% confidence intervals (CIs). RESULTS: Across all five seasons, 1767 children were enrolled, and 711 (40%) tested RSV‑positive. In 2024‑25 specifically, 359 children were enrolled, of whom 145 (41%) were RSV‑positive. The overall mean illness duration was 15.5 days (SD 8.9), with 38.4% still symptomatic at Day 14 and 15.9% at Day 30. Hospitalization occurred in 7 (4.8%) of RSV‑positive cases in 2024‑25 (overall 4.5 % across all seasons), with a median stay of 6 days (IQR 4-8). Estimated hospitalization risk at birth was 11% (95% CI: 3.7-22.5%), declining below 1% at 51 months. CONCLUSIONS: Including 2024‑25 data did not change our earlier estimates: RSV continues to cause prolonged illness in primary care, and infants bear the highest hospitalization risk. These updated, age-stratified risk estimates are critical inputs for the evaluation of RSV prevention strategies. KEY MESSAGES: • Inclusion of 2024–25 data confirms that RSV remains a major cause of acute respiratory infections, with high hospitalization risk in children under 5 years seen in primary care in Italy. • The estimated RSV-specific hospitalization risk is highest at birth (11%, CI: 4-22%) and declines sharply with age, dropping below 1% by four years, remaining high until the age of two (3%, CI: 1-5%).