Adenovirus Types in U.S. Children Hospitalized or seen in the Emergency Department with Acute Respiratory Illness, 2016–2019

Background Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI), contributing to 5-13% of cases worldwide. Clinical manifestations vary by HAdV species and type; therefore, delineating type-specific disease presentations and understanding severity of specific HAdV types’ disease may help develop targeted interventions. Methods We conducted a multicenter, prospective study within the New Vaccine Surveillance Network to characterize HAdV types. Children <18 years old with ARI were enrolled in the emergency department or inpatient setting at seven U.S. children’s hospitals from 12/01/2016-11/30/2019. Respiratory specimens were collected and tested for HAdV and other viruses. Subsequently, typing was conducted on HAdV specimens using single-plex real-time PCR assays targeting sequences in the hexon gene. Comparisons between HAdV types were performed to determine differences in characteristics and outcomes. Generalized linear mixed effects models were used to evaluate severity. Results Among the 1,843 HAdV-positive cases, 1,402 specimens (76%) were typed. The most common types detected were HAdV-C1 (n=439), HAdV-C2 (n=393), and HAdV-B3 (n=221). Children with HAdV-B7 (n=78) had higher odds of severe outcomes compared to those with other HAdV types (aOR=2.05; 95% CI: 1.24, 3.40). Symptom presentation varied across types within species B, C, and E; while all species had high frequency of upper respiratory symptoms, species B cases presented with a higher frequency of non-respiratory manifestations. Conclusions Among children with HAdV-positive ARI, those with HAdV-B7 had higher odds of severe outcomes. These findings suggest heterogeneity in clinical presentation and severity among HAdV types, emphasizing the importance of HAdV type in future prevention and treatment strategies.