Int J Biol Sci 2022; 18(12):4648-4657. doi:10.7150/ijbs.72963 This issue

Research Paper

Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance

Shanshan Cao2,11,#, Qing Zhang3,#, Liu Song1,11,#, Mingzhong Xiao3,#, Yexing Chen1,11,#, Dianbing Wang1, Min Li1, Jinchao Hu2, Lin Lin1, Ying Zheng2,11, Kun Zhou2,11, Shujian Ye1, Juan Zhou2,11, Ya Na Zhou3, Jing Cui2,8, Jingzhi Wang3, Jing Sun3, Junxiu Tao3, Zhou Chen9, Rong Chen10, Peng Zhou2, Zhengli Shi2, Sheng Wei6, Linhua Zhao4, Hui Wang6,✉, Xiaoling Tong4,✉, Xiaodong Li3,✉, Dong Men2,11,✉, Baidong Hou1,11,✉, Xian-En Zhang1,7,✉

1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2. State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
3. Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430074, China
4. Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
5. Wuchang District Health Bureau, Wuhan 430060, China
6. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
7. Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
8. Hubei University, Wuhan 430074, China
9. Wuchang District Hospital of Traditional Chinese Medicine, Wuhan 430060, China
10. Jiyuqiao Street Community Health Service Center, Wuchang District, Wuhan 430081, China
11. University of Chinese Academy of Sciences, Beijing 100049, China
# These authors contributed equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Cao S, Zhang Q, Song L, Xiao M, Chen Y, Wang D, Li M, Hu J, Lin L, Zheng Y, Zhou K, Ye S, Zhou J, Zhou YN, Cui J, Wang J, Sun J, Tao J, Chen Z, Chen R, Zhou P, Shi Z, Wei S, Zhao L, Wang H, Tong X, Li X, Men D, Hou B, Zhang XE. Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance. Int J Biol Sci 2022; 18(12):4648-4657. doi:10.7150/ijbs.72963. Available from

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Graphic abstract

Asymptomatic infection with SARS-CoV-2 is a major concern in the control of the COVID-19 pandemic. Many questions concerning asymptomatic infection remain to be answered, for example, what are the differences in infectivity and the immune response between asymptomatic and symptomatic infections? In this study, based on a cohort established by the Wuchang District Health Bureau of Wuhan in the early stage of the COVID-19 pandemic in Wuhan in 2019, we conducted a comprehensive analysis of the clinical, virological, immunological, and epidemiological data of asymptomatic infections. The major findings of this study included: 1) the asymptomatic cohort enrolled this study exhibited low-grade but recurrent activity of viral replication; 2) despite a lack of overt clinical symptoms, asymptomatic infections exhibited ongoing innate and adaptive immune responses; 3) however, the immune response from asymptomatic infections was not activated adequately, which may lead to delayed viral clearance. Given the fragile equilibrium between viral infection and host immunity, and the delayed viral clearance in asymptomatic individuals, close viral monitoring should be scheduled, and therapeutic intervention may be needed.

Keywords: COVID-19, SARS-CoV-2, asymptomatic infection, inflammatory cytokine, immune repertoire, epidemiological investigation