High case fatality rate of human adenovirus type 7 infections in children: a meta-analysis and phylogenetic study of HAdV-7 epidemics over the past seven decades

Human adenovirus type 7 (HAdV-7) is a significant respiratory pathogen associated with severe infections, particularly among children and military populations. Despite numerous reported outbreaks, comprehensive data on its case fatality rate (CFR) are scarce. We conducted a meta-analysis of 305 PubMed articles (1954-2023) and phylogenetic analyses of 313 HAdV-7 genomes and capsid protein gene sequences available in GenBank, and estimated temporal evolutionary dynamics using Bayesian methods. Our analysis identified 16,100 HAdV-7 cases with 388 deaths (CFR: 2.41%), of which 87.63% (340) occurred in children. Cases were reported globally, except in Antarctica; Asia had the highest number (10,827), followed by North America and Europe. Mainland China recorded the most fatalities (150), followed by the United States and South Korea (53 and 39, respectively). HAdV-7 primarily infected the respiratory system (11,617 cases, 72.16%), followed by the gastrointestinal systems (957 cases, 5.94%), with limited central nervous system involvement (126 cases, 0.78%). A literature search on HAdV-related fatalities across six HAdV species identified 667 deaths, of which HAdV-7 was the dominate type (262 cases, 39.28%). Phylogenetic analysis revealed three variants (7V, 7E1, 7E2). The 7E2 variant, dominant after 2005, was associated with more deaths (91 cases, 67.91%) than 7E1 variant (43 cases, 32.09%). Bayesian analysis estimated a substitution rate of 3.89 × 10^-⁵ mutations/site/year. This study combines large-scale meta-analyses and evolutionary studies to characterize the biological and epidemiological features of HAdV-7, providing insights for vaccine development and highlighting the need for effective vaccines and antivirals.