• Qing Lei, Yang Li, Hong-Yan Hou, Feng Wang, Zhu-Qing Ouyang, Yandi Zhang, Dan-Yun Lai, Jo-Lewis Banga Ndzouboukou, Zhao-Wei Xu, Bo Zhang, Hong Chen, Jun-Biao Xue, Xiao-Song Lin, Yun-Xiao Zheng, Zong-Jie Yao, Xue-Ning Wang, Cai-Zheng Yu, He-Wei Jiang, Hai-Nan Zhang, Huan Qi, Shu-Juan Guo, Sheng-Hai Huang, Zi-Yong Sun, Sheng-Ce Tao, and Xiong-Lin Fan.
• Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
• Allergy. 2021 Feb 1; 76 (2): 551-561.

BackgroundThe missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.MeasureUtilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.ResultsA combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.ConclusionOur findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.© European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

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