Abstract
Human adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Studies on comparative viral genomic analysis of cases associated with severe and mild infections due to HAdV are limited. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. 2 million inhabitants. The HAdV species implicated in causing severe infections in this study included HAdV species C genotypes (HAdV1, HAdV2, and HAdV5). Clustering of the HAdV whole-genome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. This isolate showed intertypic recombination events involving four genotypes, had the highest homology to HAdV89 at complete genome level, but possessed the fiber gene of HAdV1, thereby representing a novel genotype of HAdV species C. The incidence of potential recombination events was higher in severe cases than in mild cases. Our findings confirm that recombination among HAdVs is important for molecular evolution and emergence of new strains. Therefore, further research on HAdVs, particularly among susceptible groups, is needed and continuous surveillance is required for public health preparedness including outbreak investigations.
Highlights
Human adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population
Over 100 genotypes of HAdVs are recognized by the Human Adenovirus Working Group July, 2019 Update, which are classified into seven species/groups (HAdV-A to HAdV-G) initially defined on the basis of their physical, chemical and biological properties by serum neutralization methods, but more recently distinguished based on whole-genome sequencing (WGS), genomic and bioinformatic analysis
The complete genomes of HAdV isolates from pediatric patients presenting with severe cases including meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization were analyzed alongside those obtained from HAdV pediatric patients presenting with mild cases (Table 1)
Summary
Human adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. Clustering of the HAdV wholegenome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. The aim of our study was to determine if there were any genomic differences between circulating HAdV strains causing severe and mild clinical presentations in hospitalized pediatric patients in Bern, Switzerland. Our results document that recombination is a major factor for HAdV evolution and may possibly contribute to disease severity
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