Molecular characterization of Adenovirus genotypes and clinical implications in pediatric patients
Background Human adenoviruses (HAdV) are classified into 116 genotypes grouped into seven species with remarkable difference in term of tropism and species-specific immune-response. HAdVs cause a wide variety of clinical manifestations that can be severe in immunocompromised patients.  The aim of our study was to characterize HAdV species involved in pediatric infection, in order to understand their potential impact on disease progression and to guide the selection of therapies based on AdV-specific T-cell response. Materials and Methods From January-October 2024, 595 new HAdV diagnoses were performed in pediatric patients at the Bambino Gesù Children Hospital (Rome). Among them, 60 positive specimens (53 stool; 7 nasopharyngeal-swabs) were randomly selected for HAdV Whole-genome-sequencing (WGS) using Illumina-MiSeq.   Results Among the 60 selected patients, 45(75%) were immunocompetent with a median age of 1.4 years (IQR:0.74–2.61) and 15(25%) were immunocompromised with a median age of 12.5 years (IQR:4.99–15.85). Most of them (55/60,91.5%) were hospitalized. At HAdV diagnosis, gastrointestinal and respiratory symptoms were most prevalent in immunocompetent than immunocompromised patients (91.1%vs72.7% and 53.3%vs27.3%, respectively). However, the immunocompromised have shown a longer length of hospitalization and viral-infection (p<0.001). Overall, the majority of HAdV (63.3%) belonged to species-F (specifically F41), followed by species-C (25%), -A (8.3%) and –B (3.3%). Moreover, a higher prevalence of genotype-F41 was observed in immunocompetent patients (75.6%vs26.7%; p=0.001). Differently, immunocompromised patients had higher rates of species-A (26.7%vs2.2%; p=0.012) and species-C (40% vs 20%; p=0.169), the latter already known to cause severe infections in children and immunocompromised patients. Conclusions Our results showed a different distribution of HAdV-strain between immunocompromised and immunocompetent patients. In particular, species-F was most prevalent in immunocompetent patients with gastrointestinal and respiratory symptoms. Otherwise HAdV species-C and species-A characterized immunocompromised patients.  A closer screening and the use of WGS will be essential in immunocompromised setting to anticipate the time of HAdV diagnosis and to improve HAdV surveillance. This study is a starting point, to identify which HAdV-genotypes are likely to be more severe, to identify specific genes that make a strain more harmful and to guide selection of an appropriate cell therapy.