Pathogen and Patient Characteristics and the Severity of Viral Respiratory Infections in Children.

Importance: Respiratory infections are a leading cause of pediatric hospitalization and impose a significant burden on health care systems. Objectives: To evaluate clinical outcomes and risk factors for severe disease in hospitalized children with viral respiratory infections, focusing on the role of etiologies, comorbidities, age, and coinfections. Design, Setting, and Participants: This multicenter observational cohort study is part of an active pediatric surveillance system established in September 2023, within the framework of the European Union-funded National Recovery and Resilience Plan. The One Health Basic and Translational Actions Addressing Unmet Needs on Emerging Infectious Diseases (INF-ACT) network, which includes 12 pediatric infectious disease referral centers across Italy, is designed to enable early detection of emerging infectious threats in children. The network is based on 3 pillars: monthly online meetings, a register of cases of unusual severity or induced by unusual pathogens, and a sample repository to investigate microbiology or host-related risk factors. Hospitalized children with respiratory symptoms and confirmed or suspected viral infection between September 2023 and December 2024 were eligible. Exposures: Type of respiratory virus, viral or bacterial coinfections, and presence of chronic comorbidities. Main Outcomes and Measures: Severity was assessed using a clinical severity score (CSS), with a score greater than 3 indicating severe disease. The CSS considered mechanical ventilator support, hospital admission, length of hospital stay, oxygen saturation level, and use of supplemental oxygen. Length of hospital stay, intensive care unit admission, and the need for oxygen therapy were also considered as individual outcomes. Results: Of 516 children hospitalized with respiratory symptoms (median [IQR] age, 13.3 [4.0-43.0] months; 288 male [55.8%]), 34 (6.6%) had severe disease (CSS >3). In multivariable analysis, among patients with respiratory symptoms, infection with respiratory syncytial virus (10 of 67 [14.9%]; adjusted odds ratio [AOR], 4.26 [95% CI, 1.80-10.10]) or influenza (14 of 104 [13.5%]; AOR, 4.13 [95% CI, 1.88-9.04]) and the presence of cardiac or pulmonary diseases (4 of 18 [22.2%]; AOR, 5.25 [95% CI, 1.47-18.78]) or congenital malformations (3 of 14 [21.4%]; AOR, 4.94 [95% CI, 1.23-19.93]) were associated with increased risk of severe infection. A higher ICU admission rate was observed in children with influenza infection (12 of 104 [11.5%] vs 9 of 412 [2.2%]; P < .001) and preexisting comorbidities (9 of 69 [13.0%] vs 12 of 447 [2.7%]; P < .001). Age and coinfections were not significantly associated with worse outcomes. Conclusions and Relevance: In this cohort study of hospitalized children, respiratory syncytial virus and influenza infections, as well as the presence of chronic comorbidities, were significantly associated with severe disease. These findings support the need for targeted prevention and vaccination strategies, as well as early identification of children at risk for severe disease. The INF-ACT network offered a scalable model for real-time infectious disease monitoring in pediatric populations.