Molecular subtypes of respiratory Adenovirus infection outbreak in children in Northern Vietnam and risk factors of more severe cases

Background: Under the pressure of the outbreak of respiratory Human Adenovirus (HAdV) infections in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) responsible for the outbreak in relation to the clinical features of the patients and examine the risk factors of more severe cases. Methods: The study was conducted on pediatric patients tested positive with HAdV using multiplex real-time PCR between October and November 2022. Nasal swab samples were used for sequencing to identify HAdV subtypes and clinical data were collected retrospectively. Results: Among 97 successfully sequenced samples, the predominant subtypes were HAdV-B3 (83%), HAdV-B7 (16%) and HAdV-C2 (1%). Lower respiratory manifestations were found in 25% of patients (5% with severe pneumonia). There was no significant association between HAdV type and clinical features except that those infected with HAdV type 3 exhibited higher WBC and neutrophil % (p<0.001). Co-infection of HAdV with ≥1 other respiratory viruses or bacteria was found in 70.8% of those with lower respiratory illnesses (OR (95%CI); p-value vs. those without =5.21 (1.60, 19.36); 0.0084 after adjusting for age at hospital visit, sex, birth delivery method, day of disease at hospital visit), and in 100% of those with severe pneumonia vs. 33% of those without (p=0.005).   Conclusion: HAdV-B3 and HAdV-B7 were predominant in the outbreak. Co-infection of HAdV together with other respiratory viruses or bacteria was a strong risk factor for lower respiratory tract illnesses and severe pneumonia. The findings advocate the advantages of multi-factor microbial panels for the diagnosis and prognosis of respiratory infections in children. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Research & Development fund of Vinmec High-tech Centre, Vinmec Healthcare System. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Vinmec IRB. Reference number: 152/2022/CN-HDDD VMEC I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.