The pathogenesis of human adenovirus type 7 (HAdV-7)-induced severe disease was likely associated with high replication competence and hyperinflammatory responses, according to data published in the Journal of Infectious Diseases.

The most severe or fatal adenoviral disease in children, according to epidemiological reports, is associated with HAdV-7. Therefore, to better clarify the pathogenesis of HAdV-7-induced severe disease, investigators compared HAdV-3 and HAdV-7 replication kinetics and the host response to infection using ex vivo human lung tissue cultures. They further measured the cytokine/chemokine levels and the presence of adenovirus DNA in the serum of 65 and 48 hospitalized children infected with HAdV-7 and HAdV-3, respectively.

Among 471 human adenovirus positive specimens, HAdV-3 or HAdV-7 was the most prevalent genotype between 2014 and 2016 or in 2018, respectively. The incidence of severe pneumonia was higher in individuals infected with HAdV-7 (30.1%) compared with those with HAdV-3 infections (4.5%). HAdV-7 also replicated more efficiently ex vivo. In children infected with HAdV-7 versus HAdV-3, interferon gamma-induced protein (IP)-10, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly higher. Adenovirus DNA was also detected in the serum of 40% and 4.2% of children with HAdV-7 or HAdV-3 infection, respectively. Investigators further reported that viremia was strongly associated with severe clinical presentations.

Several limitations to this study were noted by investigators, including the absence of epidemiological or clinical data on children infected with adenovirus in 2017. They also acknowledge that the ex vivo human lung tissue explant culture is short-lasting and does not represent the effect of host systemic inflammatory response and the adaptive immune response. In order to elucidate additional details on the pathogenesis of HAdV-7 during pulmonary and extrapulmonary involvement, they suggest further studies using both ex vivo lung and intestinal organoids.


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“HAdV-7 virus caused more severe disease characteristics and outcomes, and the pathogenesis was most likely associated with high replication competence and hyperactive cytokine-mediated inflammatory response,” the researchers concluded. Furthermore, they believe that the detection of adenovirus DNA in blood allowed for the diagnosis of disseminated infection. Finally, the investigators believe this work will help to design novel therapeutic approaches for pediatric patients with HAdV-7 infections.

Reference

Chen Q, Liu J, Liang W, et al. Clinical features, replication competence, and innate immune responses of adenovirus type 7 infection in humans [published online August 25, 2020]. J Infect Dis. doi: 10.1093/infdis/jiaa524