Abstract
Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for acute respiratory tract infection (ARTI) in young children. Respiratory viral coinfections are frequently identified in RSV-related ARTIs, yet their impact on disease severity remains controversial and may vary according to the co-pathogen involved. In the context of evolving RSV prevention strategies, a clearer understanding of RSV coinfection phenotypes is needed. Methods: We conducted a multicenter retrospective cohort study of children aged ≤ 5 years hospitalized for ARTI at two Italian tertiary-care pediatric hospitals between 1 September 2022 and 30 April 2025. Children with laboratory-confirmed RSV infection detected by multiplex polymerase chain reaction were included. Patients were classified as having RSV monoinfection, RSV-rhinovirus coinfection, or RSV-non-rhinovirus coinfection. Severe disease was defined as a composite outcome including intensive care unit (ICU) admission, need for respiratory or hemodynamic support, or death. Association between infection status and severe disease was evaluated using a Poisson regression model with robust variance, adjusted for age, sex, and comorbidities. Results: Among 231 RSV-related hospitalizations, 118 (51.1%) were classified as RSV monoinfection, 65 (28.1%) as RSV-rhinovirus coinfection, and 48 (20.8%) as RSV-non-rhinovirus coinfection. Children with RSV-rhinovirus coinfection were older and had shorter hospital stays. Severe disease occurred in 80.5% of RSV monoinfections, 70.8% of RSV-rhinovirus coinfections, and 75.0% of RSV-non-rhinovirus coinfections. After adjustment, neither RSV-rhinovirus coinfection (adjusted risk ratio [aRR]: 0.93; 95% confidence interval [95% CI]: 0.80-1.13) nor RSV-non-rhinovirus coinfection (aRR: 0.99; 95% CI: 0.83-1.18) was associated with increased disease severity compared with RSV monoinfection. Conclusions: RSV-rhinovirus and RSV-non-rhinovirus coinfections were not associated with greater disease severity compared with RSV monoinfection in hospitalized children. These findings support pathogen-specific interpretation of multiplex diagnostic results and inform clinical risk stratification in the era of expanding RSV prevention strategies.