High Pathogenicity of Human Adenovirus Type 55 in Adult Males: A Meta-Analysis and Phylogenetic Study of HAdV-55 Epidemics Worldwide Over the Past Six Decades

Human adenovirus type 55 (HAdV-55), formerly designated as HAdV-11a, is a notable recombinant pathogen linked to severe respiratory infections. Since its reclassification as HAdV-55 in 2010, numerous outbreaks of pneumonia associated with it have been documented over the past decade. We conducted a systematic review of 111 peer-reviewed articles from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) spanning the 60 years (1965-2024). Furthermore, we performed phylogenetic analysis on 87 complete HAdV-55 genomes available in GenBank. Bayesian methods were employed to estimate the temporal evolutionary dynamics of HAdV-55. A total of 15,245 HAdV-55 cases were identified, including 3,790 pneumonia cases (24.86%) and 33 fatalities (case fatality rate: 0.22%), of which 21 (63.63%) were male and the remainder unspecified. Military recruits comprised 79.06% of the cases (12,039/15,245), with adults (95.39%) and males (97.61%) predominantly affected. Asia accounted for the majority of cases (15,060, 98.79%), primarily in China (89.90%), followed by North America (0.98%). The infections caused by HAdV-55 are associated with respiratory (87.27%), gastrointestinal (2.71%), ocular (0.30%), and mental (0.07%) disorders. Phylogenetic analysis identified four variants: HAdV-55a through HAdV-55d, with HAdV-55d emerging as the dominant circulating strain since 2006. Additionally, the E3 region harbors distinct amino acid substitutions correlated with specific countries, suggesting evolution for immune evasion. Bayesian evolutionary analysis estimated the most recent common ancestor (tMRCA) originated in 1929 (95% HPD: 1890-1967). This study underscores the high prevalence of HAdV-55 among adults and males, particularly in China, highlighting the urgent necessity for antiviral therapeutics and vaccines.