Clinical presentation and hospitalisation risk of RSV in primary care among children younger than 5 years in Italy in four seasons between 2019 and 2023: a multicentre prospective cohort study.

Background: Respiratory syncytial virus (RSV) significantly contributes to pediatric morbidity globally. Severe cases are more common in infants and children with underlying health conditions, but even mild infections can result in long-term respiratory issues. While the RSV disease is well-documented in hospital settings, its clinical presentation and hospitalization risk in primary care, the initial point of healthcare access, remains unclear. Methods: We conducted a multi-center prospective cohort study across multiple regions in Italy during four seasons (from 2019 to 2020 to 2023-2024), excluding 2020-2021. Children ≤5 years with acute respiratory infection (ARI), meeting the WHO case definition for community-based surveillance, were enrolled through primary care pediatricians. Nasopharyngeal swabs were collected and tested with RT-PCR. Clinical data were collected at baseline for all participants and at follow-up intervals of 14 and 30 days post-enrollment for RSV-positive children. Findings: Among 1410 enrolled children with ARIs, RSV was laboratory-confirmed in 40.2% (n = 566). The mean duration of illness among RSV-positive children was 15.2 days (SD 8.8 days), with symptoms persisting in 40.9% of cases at day 14 and 15.4% at day 30. Hospitalization occurred in 4.4% (25/566) of RSV-positive cases, with a median hospital stay of 5 days (IQR: 4-7 days). Younger age was identified as the primary predictor of hospitalization (observed hospitalization rate of 16.2% in children under 6 months), with an estimated hospitalization risk of 12.5% at birth (95% CI: 3.4-33.1%). Fever did not differentiate RSV infection from other respiratory pathogens (p = 0.084). Interpretation: Our study highlights the significant hospitalization risks associated with RSV infections among children presenting in primary care settings, offering detailed age-specific risk estimates crucial for accurate health technology assessments (HTAs) of preventive strategies. The findings strongly support exploring the expansion of RSV preventive interventions beyond the conventional age threshold of 24 months, considering the persisting risk in older children. Furthermore, we emphasize the importance of adopting a case definition without a mandatory fever criterion to enhance the sensitivity of RSV surveillance and thus improve the validity of disease-related estimates. Funding: RSV ComNet is a collaborative study funded by Sanofi and AstraZeneca. Study design and planning were undertaken in collaboration with Sanofi researchers. All data collection, analyses, interpretation, manuscript drafting, and the decision to submit for publication were performed independently by the authors. No datasets were shared with the funding parties.