Respiratory Viral Co-Infections in Pediatric Patients: Clinical Impact and Implications for Healthcare Practice—A Narrative Review

Background: Respiratory viral infections remain a major cause of morbidity and hospitalization in children. The increased use of multiplex molecular assays has improved the detection of simultaneous viral pathogens, raising questions about the clinical relevance of pediatric viral co-infections. Objective: The aim of this study is to synthesize recent evidence on respiratory viral co-infections in children, focusing on clinical severity, healthcare burden, mechanisms, and interpretation of multiplex detections. Methods: This narrative review included studies published between 1 January 2022 and 30 September 2025, identified through PubMed and Web of Science. Eligible studies involved children and adolescents (0–18 years) with laboratory-confirmed respiratory viral co-infections, mainly detected by multiplex PCR. Evidence was synthesized qualitatively across severity, neutral or inconsistent impact, viral interference, and post-acute implications. Results: Forty-five studies were included. The most frequently reported viruses were respiratory syncytial virus (RSV), rhinovirus, adenovirus, influenza virus, and human metapneumovirus (HMPV). Clinical impact was heterogeneous and depended more on specific viral pairings and host factors than on the number of detected viruses. RSV-containing combinations, particularly with HMPV, adenovirus, or rhinovirus, were more often linked to increased respiratory burden, whereas some rhinovirus-associated combinations appeared compatible with viral interference. Conclusions: Pediatric respiratory viral co-infection is clinically relevant but context-dependent. Multiplex results should be interpreted together with clinical, laboratory, and radiological findings.