Fatal Neonatal Sepsis Associated with Human Adenovirus Type 56 Infection: Genomic Analysis of Three Recent Cases Detected in the United States

Abstract

Background: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020. Methods: Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank. Results: The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s. Conclusion: As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.