Whole-Genome Sequencing of Adenovirus Genotypes and Clinical Implications in Pediatric Patients.

Human adenoviruses (HAdV) comprise more than 100 genotypes with species-specific differences in tropism and immune response and can cause severe infections in immunocompromised patients. This study aimed to characterise the HAdV species involved in pediatric infections to assess their clinical impact and guide future therapeutic strategies based on AdV-specific T-cell responses. Between January and October 2024, 595 pediatric HAdV diagnoses were made at the Bambino Gesù Children's Hospital (Rome), and whole-genome sequencing was performed on 60 samples. Most patients (91.7%) were hospitalised, including both immunocompetent (75%) and immunocompromised (25%) children. Gastrointestinal and respiratory symptoms were more common in immunocompetent patients, whereas immunocompromised patients experienced longer hospitalisations and persistent viral infections. Species F (F41) was most prevalent (63.3%), especially among immunocompetent patients, while species C and A predominated in immunocompromised children, with species A associated with severe disease. Viral loads were significantly higher for species F than for species A and C, independent of immune status. Co-infections were frequent (63.3%), with species C particularly linked to them. In conclusion, HAdV distribution differed by immune status, with species F predominating in immunocompetent children and species C and A more common in immunocompromised patients. Whole-genome sequencing may enhance surveillance, enable earlier diagnosis, and support the development of genotype-specific immunotherapies.