Impact of Co-infections and Immune Responses on Clinical Severity of Human Adenovirus 3 and 7 Infections in Hospitalized Children with Lower Respiratory Tract Infections: a Comparative Study

Overview

Journal Front Cell Infect Microbiol

Date 2025 Jan 24

PMID 39850965

Authors

Xiaolin Ma

Yuting Wu

Ri De

Hailan Yao

Feng He

Yi Wang

Wei Wang

Chao Yan

Qinwei Song

Chunjie Guo

Li Wen

Linqing Zhao

Ling Cao

Chunmei Zhu

Affiliations

Soon will be listed here.

Abstract

Background: The pathogenic distribution of co-infections and immunological status of patients infected with human adenovirus serotypes 3 or 7 (HAdV-3 or HAdV-7) were poorly understood.

Methods: This study involved a retrospective analysis of respiratory specimens collected from enrolled children with lower respiratory tract infections (LRTIs), positive for HAdV-3 or HAdV-7 from January 2017 to December 2019. Demographic data, clinical features, laboratory and radiographic findings were compared to delineate the impact of co-infections, and immune responses on clinical severity of HAdV-3 or HAdV-7 infections.

Results: Among 1311cases enrolled, there were 66 infected with HAdV-3 and 58 with HAdV-7. HAdV-7-infected patients exhibited more prolonged fever (100% vs 89.4%, =0.014), pneumonia (100% vs 89.4%, =0.014), hypoxia (34.5% vs 12.1%, =0.003), higher propensity for aspartate aminotransferase exceeding 80U/L (21.1% vs 4.7%, =0.006), D-Dimer exceeding 1.65mg/L (64.9% vs 12.5%, <0.001), consolidation (50.0% vs 27.4%, =0.011), and pleural effusion (32.8% vs 6.5%, p<0.001), co-infections with (77.1% vs 32.6%, <0.001), and multiple infections (56.8% vs 41.3%, =0.007), compared to those with HAdV-3 infections. Immune cell analysis indicated that HAdV-7 infections led to a more pronounced decrease in CD3+ T cells (1596.8 vs 2444.8 cells/????l, p=0.042), CD8+ cytotoxic T cells (668.6 vs 774.0 cells/µl, =0.045), and increased NK cell percentages (11.5% vs 9.0%, =0.044) compared to HAdV-3 infections.

Conclusions: Hospitalized children with HAdV-7-associated LRTIs exhibit greater severity, multiple infections, and significant potential for greater cellular immune dysregulation compared to those with HAdV-3 infection, indicating a more severe clinical course and distinct pathogenic profiles.

References

Liu Y, Zhang Y, Xu Q, Qiu Y, Lu Q, Wang T . Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study. Lancet Microbe. 2023; 4(5):e330-e339. DOI: 10.1016/S2666-5247(23)00031-9. View

Mao N, Zhu Z, Zhang Y, Xu W . Current status of human adenovirus infection in China. World J Pediatr. 2022; 18(8):533-537. PMC: 9206124. DOI: 10.1007/s12519-022-00568-8. View

Li Z, Zhang H, Ren L, Lu Q, Ren X, Zhang C . Etiological and epidemiological features of acute respiratory infections in China. Nat Commun. 2021; 12(1):5026. PMC: 8373954. DOI: 10.1038/s41467-021-25120-6. View

Liu W, Qiu S, Zhang L, Wu H, Tian X, Li X . Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019. Virol Sin. 2022; 37(3):331-340. PMC: 9243629. DOI: 10.1016/j.virs.2022.01.010. View

Wu X, Zhang J, Lan W, Quan L, Ou J, Zhao W . 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. Front Microbiol. 2022; 13:911694. PMC: 9133664. DOI: 10.3389/fmicb.2022.911694. View

Cherian T, Mulholland E, Carlin J, Ostensen H, Amin R, de Campo M . Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ. 2005; 83(5):353-9. PMC: 2626240. DOI: /S0042-96862005000500011. View

Yang C, Zhu C, Qian Y, Deng J, Zhang B, Zhu R . Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection. Virol Sin. 2020; 36(3):393-401. PMC: 7527426. DOI: 10.1007/s12250-020-00299-y. View

Gao J, Xu L, Xu B, Xie Z, Shen K . Human adenovirus Coinfection aggravates the severity of Mycoplasma pneumoniae pneumonia in children. BMC Infect Dis. 2020; 20(1):420. PMC: 7296888. DOI: 10.1186/s12879-020-05152-x. View

Xie L, Zhang B, Xiao N, Zhang F, Zhao X, Liu Q . Epidemiology of human adenovirus infection in children hospitalized with lower respiratory tract infections in Hunan, China. J Med Virol. 2018; 91(3):392-400. PMC: 7159165. DOI: 10.1002/jmv.25333. View

10.

Chen Y, Lin T, Wang C, Liang W, Lian G, Zanin M . Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study. World J Pediatr. 2022; 18(8):545-552. PMC: 9302229. DOI: 10.1007/s12519-022-00590-w. View

11.

Li L, Woo Y, de Bruyne J, Nathan A, Kee S, Chan Y . Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia. PLoS One. 2018; 13(10):e0205795. PMC: 6188781. DOI: 10.1371/journal.pone.0205795. View

12.

Zhou W, Chen J, Xi Z, Shi Y, Wang L, Lu A . Characteristics of Lung Microbiota in Children's Refractory Pneumonia Coinfected with . Can J Infect Dis Med Microbiol. 2022; 2022:7065890. PMC: 8786547. DOI: 10.1155/2022/7065890. View

13.

Wang L, Hu X, Huang Z, Zhang Y, Zhao X, Liu X . Analysis of the typing of adenovirus and its clinical characteristics in children with acute respiratory tract infection. BMC Pediatr. 2023; 23(1):25. PMC: 9841135. DOI: 10.1186/s12887-023-03840-6. View

14.

Wei J, Wu S, Jin X, Zhang J, Pan S . Association of coinfection with adenovirus pneumonia severity in children. Allergol Immunopathol (Madr). 2021; 50(1):31-36. DOI: 10.15586/aei.v50i1.476. View

15.

Lin M, Yang S, Gong Y, Kuo C, Chiu C, Chen C . Clinical and molecular features of adenovirus type 2, 3, and 7 infections in children in an outbreak in Taiwan, 2011. Clin Microbiol Infect. 2016; 23(2):110-116. PMC: 7129580. DOI: 10.1016/j.cmi.2016.11.004. View

16.

Tamura K, Nei M, Kumar S . Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A. 2004; 101(30):11030-5. PMC: 491989. DOI: 10.1073/pnas.0404206101. View

17.

Kumar S, Stecher G, Li M, Knyaz C, Tamura K . MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol. 2018; 35(6):1547-1549. PMC: 5967553. DOI: 10.1093/molbev/msy096. View

18.

Wang F, Yang C, Qian Y, Li F, Gu L, Chen D . [Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing]. Zhonghua Er Ke Za Zhi. 2022; 60(1):30-35. DOI: 10.3760/cma.j.cn112140-20210809-00658. View

19.

Chen Y, Liu F, Wang C, Zhao M, Deng L, Zhong J . Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013. PLoS One. 2016; 11(5):e0155412. PMC: 4865050. DOI: 10.1371/journal.pone.0155412. View

20.

Cai S, Zhu C, Chen F, Liu F, Gao M, Xiong Y . [Establishment of a risk model for severe adenovirus pneumonia and prospective study of the timing of intravenous immunoglobulin therapy in children]. Zhongguo Dang Dai Er Ke Za Zhi. 2023; 25(6):619-625. PMC: 10321423. DOI: 10.7499/j.issn.1008-8830.2211069. View