{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:11:59Z","timestamp":1791839519011,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human Adenovirus (HAdV) is a significant pathogen for acute respiratory infections(ARIs) in children. However, its epidemiological patterns, serotype distribution changes, and molecular mechanisms associated with severe pneumonia during and after the COVID-19 pandemic require further elucidation through large-scale and molecular typing studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study used a retrospective cohort design to analyze 28060 respiratory specimens from Tianjin Children\u2019s Hospital from March 2022 to March 2024. HAdV detection and typing were performed through targeted high-throughput sequencing and PCR-based amplification of Penton, Hexon, and Fiber genes for phylogenetic analysis. Additionally, clinical data were compared to assess differences in clinical presentations among pediatric patients infected with different HAdV types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The overall HAdV detection rate was 8.9% (2,484\/28,060), with significant male predominance (9.2% <jats:italic>vs<\/jats:italic>. 8.4%, <jats:italic>P<\/jats:italic> = 0.019) and age-specific susceptibility peaking in school-aged children (10.4%, <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Seasonal patterns demonstrated winter predominance (15.9%), contrasting with other seasons (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). Genotyping of 1,914 positive specimens demonstrated HAdV-3 dominance (53.4%, 1,022), followed by HAdV-7 (17.7%, 338), HAdV-2 (8.4%, 160), HAdV-1 (7.9%, 152), and HAdV-21 (6.4%, 122). The diagnosis mainly included pneumonia, bronchitis, adenopharyngitis, and upper respiratory tract infections (URTIs). Genotype-clinical correlations showed distinct patterns: HAdV-3 (55.6%) and HAdV-7 (20.9%) predominated in pneumonia cases, with HAdV-7 linked to severe pneumonia (<jats:italic>P<\/jats:italic>&amp;lt;0.001). HAdV-3 (40.6%) and HAdV-2 (16.7%) were more common in adenopharyngitis, while HAdV-3 and HAdV-21 were more common in bronchitis (51.2% and 11.1%) and URTIs (31.9% and 19.1%). Molecular characterization revealed structural conservation in the Penton protein of HAdV-C and identified Hexon as the most polymorphic region with 85 variable sites, indicating divergent evolutionary pressures across viral domains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HAdV-3, HAdV-7, HAdV-2, and HAdV-1 were the predominant HAdV types in children hospitalized with ARIs in Tianjin. Moreover, not only the epidemiological characteristics of different HAdV types vary, but there are also certain differences in the clinical symptoms and outcomes of children infected with different types of HAdV. Therefore, it is essential to differentiate HAdV types for epidemiological surveillance and clinical management purposes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1600990","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:25:38Z","timestamp":1752470738000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Epidemiological, clinical, and molecular analysis of human adenovirus infections in hospitalized children with acute respiratory infections in Tianjin, China"],"prefix":"10.3389","volume":"15","author":[{"given":"Yulian","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhu","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/jmv.23678","article-title":"Prevalence and quantitation of adenovirus DNA from human tonsil and adenoid tissues","volume":"85","author":"Alkhalaf","year":"2013","journal-title":"J. Med. Virol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jcv.2018.04.012","article-title":"Molecular epidemiology of human adenovirus infections in Denmark, 2011-2016","volume":"104","author":"Barnadas","year":"2018","journal-title":"J. Clin. Virol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens14030262","article-title":"Epidemiology, clinical significance, and diagnosis of respiratory viruses and their co-infections in the post-COVID era","volume":"14","author":"Contes","year":"2025","journal-title":"Pathogens."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3651-2","article-title":"Human adenovirus type 7 infection causes a more severe disease than type 3","volume":"19","author":"Fu","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4909","DOI":"10.1016\/j.jinf.2014.06.015","article-title":"A human adenovirus species B subtype 21a associated with severe pneumonia","volume":"69","author":"Hage","year":"2014","journal-title":"J. Infect."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-025-01848-5","article-title":"Changes in infant respiratory pathogens pre-, during, and post-COVID-19 non-pharmacological interventions in Beijing","volume":"51","author":"Han","year":"2025","journal-title":"Ital J. Pediatr."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1237074","article-title":"Molecular epidemiology and phylogenetic analyses of human adenovirus in pediatric patients with acute respiratory infections from Hangzhou during COVID-19 pandemic","volume":"11","author":"Huang","year":"2023","journal-title":"Front. Pediatr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s12985-021-01661-6","article-title":"Human adenoviruses in paediatric patients with respiratory tract infections in Beijing, China","volume":"18","author":"Huang","year":"2021","journal-title":"Virol. J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s12985-021-01666-1","article-title":"Molecular and epidemiological characterization of human adenoviruses infection among children with acute diarrhea in Shandong Province, China","volume":"18","author":"Huang","year":"2021","journal-title":"Virol. J."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.DMIH2-0020-2015","article-title":"Adenovirus","volume":"4","author":"Ison","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.7150\/thno.105163","article-title":"Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation","volume":"15","author":"Lee","year":"2025","journal-title":"Theranostics."},{"key":"B12","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.cmi.2016.11.004","article-title":"Clinical and molecular features of adenovirus type 2, 3, and 7 infections in children in an outbreak in Taiwan, 2011","volume":"23","author":"Lin","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"B13","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.virs.2022.01.010","article-title":"Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019","volume":"37","author":"Liu","year":"2022","journal-title":"Virol. Sin."},{"key":"B14","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s12519-013-0431-3","article-title":"Clinical characteristics of adenovirus associated lower respiratory tract infection in children","volume":"9","author":"Lu","year":"2013","journal-title":"World J. Pediatr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1055\/s-0036-1584923","article-title":"Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention","volume":"37","author":"Lynch","year":"2016","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"B16","first-page":"149","article-title":"Clinical epidemiological characteristics of respiratory syncytial virus infection in children in single center in Tianjin","author":"Lyu Y","year":"2024","journal-title":"Chin. J. Microbiol. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.virol.2009.10.052","article-title":"Natural variants of human adenovirus type 3 provide evidence for relative genome stability across time and geographic space","volume":"397","author":"Mahadevan","year":"2010","journal-title":"Virology."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2019.104035","article-title":"Multiple divergent Human mastadenovirus C co-circulating in mainland of China","volume":"76","author":"Mao","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"B19","first-page":"6","article-title":"Guideline for diagnosis and treatment of community-acquired pneumonia in Children (2019 version)","volume":"12","year":"2019","journal-title":"Chin. J. Clin. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1152\/jappl.1984.56.5.1204","article-title":"Sex differences in growth patterns of the airways and lung parenchyma in children","volume":"56","author":"Pagtakhan","year":"1984","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc Physiol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2189","article-title":"Epidemiology of human adenovirus associated with respiratory infection in southern Brazil","volume":"31","author":"Pscheidt","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s12250-020-00307-1","article-title":"Seroprevalence of neutralizing antibodies against six human adenovirus types indicates the low level of herd immunity in young children from guangzhou, China","volume":"36","author":"Tian","year":"2021","journal-title":"Virol. Sin."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/v16060828","article-title":"High-frequency recombination of human adenovirus in children with acute respiratory tract infections in beijing, China","volume":"16","author":"Wang","year":"2024","journal-title":"Viruses."},{"key":"B24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.21037\/tp-23-312","article-title":"Clinical features and prediction of risk factors for severe adenovirus pneumonia in children","volume":"13","author":"Wang","year":"2024","journal-title":"Transl. Pediatr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12985-021-01705-x","article-title":"Clinical features and epidemiological analysis of respiratory human adenovirus infection in hospitalized children: a cross-sectional study in Zhejiang","volume":"18","author":"Wang","year":"2021","journal-title":"Virol. J."},{"key":"B26","first-page":"4942","article-title":"Mutation in fiber of adenovirus serotype 5 gene therapy vector decreases liver tropism","volume":"7","author":"Wang","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1186\/s12879-021-06412-0","article-title":"Molecular typing of human adenoviruses among hospitalized patients with respiratory tract infections in a tertiary Hospital in Guangzhou, China between 2017 and 2019","volume":"21","author":"Wang","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.629971","article-title":"The epidemiology, molecular, and clinical of human adenoviruses in children hospitalized with acute respiratory infections","volume":"12","author":"Wen","year":"2021","journal-title":"Front. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.911694","article-title":"Molecular typing and rapid identification of human adenoviruses associated with respiratory diseases using universal PCR and sequencing primers for the three major capsid genes: penton base, hexon, and fiber","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1186\/s12985-024-02537-1","article-title":"Comparative analysis of the epidemiological characteristics of adenovirus, rotavirus A, and coinfection in children during 2014\u20132023 in Guangzhou","volume":"21","author":"Yan","year":"2024","journal-title":"China. Virol. J."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.722885","article-title":"Epidemiology of adenovirus pneumonia and risk factors for bronchiolitis obliterans in children during an outbreak in jilin, China","volume":"9","author":"Yu","year":"2021","journal-title":"Front. Pediatr."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2019.104254","article-title":"Molecular and clinical characterization of human adenovirus associated with acute respiratory tract infection in hospitalized children","volume":"123","author":"Zhao","year":"2020","journal-title":"J. Clin. Virol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0116124","DOI":"10.1128\/spectrum.01161-24","article-title":"Epidemiology of respiratory pathogens in patients with acute respiratory infections during the COVID-19 pandemic and after easing of COVID-19 restrictions","volume":"12","author":"Zhao","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1007\/s12250-021-00437-0","article-title":"A multicenter study of viral aetiology of community-acquired pneumonia in hospitalized children in chinese mainland","volume":"36","author":"Zhu","year":"2021","journal-title":"Virol. Sin."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1600990\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:25:39Z","timestamp":1752470739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1600990\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":34,"alternative-id":["10.3389\/fcimb.2025.1600990"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1600990","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"article-number":"1600990"}}