<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSION: </strong>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.</p>

<p><strong>BACKGROUND: </strong>Human adenoviruses (HAdV) are known opportunistic pathogens in hematopoietic stem cell transplant (SCT) recipients. The detection of HAdV infection in children after SCT has been implicated as a determinant of poor outcome but specific associations between HAdV species or individual HAdV types and disease are poorly understood.</p>

<p><strong>OBJECTIVES: </strong>Characterization of a HAdV-D strain isolated from multiple clinical specimens of an 11-year-old female recipient of a matched unrelated donor peripheral SCT for T-cell lymphoma and case report.</p>

<p><strong>STUDY DESIGN: </strong>Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular typing. Complete genomic sequencing was carried out on 2 isolates.</p>

<p><strong>RESULTS: </strong>The patient tested positive for HAdV DNA by real-time PCR of a stool specimen at 44 days after initiation of a SCT conditioning regimen. In the subsequent 3 months, HAdV was detected in plasma, urine and stool specimens in association with symptoms of gastroenteritis and hemorrhagic cystitis. A novel HAdV-D with a HAdV20-like hexon gene was isolated from both urine and stool specimens. All isolates yielded identical restriction profiles with endonucleases BamHI, BglII, BstEII, HindIII, PstI and SmaI. Analysis of 2 complete genomic sequences further identified the virus as a novel intertypic recombinant HAdV-D (P20/H20/F42) closely related to HAdV42.</p>

<p><strong>CONCLUSIONS: </strong>This case highlights the identification of a previously unknown HAdV-D from an immunocompromised host. In this patient, the course of adenovirus infection is compatible with reactivation of a latent virus or a primary opportunistic infection. Adenoviremia in this patient resolved without definitive adenovirus-directed antiviral therapy.</p>