A Pediatric Case of Rapidly Progressing Disseminated Human Adenovirus C1 Infection with Multiorgan Failure and Evidence of Intra-Host Variation

A strain of human adenovirus type C1 was isolated from multiple anatomical compartments in a pediatric patient with late-onset Pompe disease. Over a period of 23 days from the appearance of fever and respiratory symptoms until death, disease progression was rapid with severe disseminated disease and complications that included respiratory distress, liver failure, cardiac dysfunction, and hemophagocytic lymphohistiocytosis. Detected viral DNAemia peaked at log10 9.52 copies/mL on the last hospitalization day. Next-generation whole-genome sequencing with depth > 2700 reads/position identified the virus as closely related to the prototype strain Adenoid 71 isolated in the US in 1953, and to strains circulating worldwide in recent years. Sequence data analysis revealed the presence of intra-host single nucleotide variants (iSNV) at low frequency in the isolates recovered from a nasopharyngeal swab, blood, urine, and stool specimens obtained during the last three days of life and from lung, liver, and kidney tissue obtained at autopsy. Evidence of iSNVs was found in only three coding regions (E1A, DNA polymerase, and pVII). Different variant combinations were found in different anatomical compartments. The contribution of intrahost genetic diversity to HAdV-associated disease development and progression warrants investigation.