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. 2021 Feb;76(2):551-561.
doi: 10.1111/all.14622. Epub 2020 Oct 26.

Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

Qing Lei  1 , Yang Li  2 , Hong-Yan Hou  3 , Feng Wang  3 , Zhu-Qing Ouyang  1 , Yandi Zhang  1 , Dan-Yun Lai  2 , Jo-Lewis Banga Ndzouboukou  1 , Zhao-Wei Xu  2 , Bo Zhang  3 , Hong Chen  2 , Jun-Biao Xue  2 , Xiao-Song Lin  1 , Yun-Xiao Zheng  2 , Zong-Jie Yao  1 , Xue-Ning Wang  2 , Cai-Zheng Yu  4 , He-Wei Jiang  2 , Hai-Nan Zhang  2 , Huan Qi  2 , Shu-Juan Guo  2 , Sheng-Hai Huang  5 , Zi-Yong Sun  3 , Sheng-Ce Tao  2 , Xiong-Lin Fan  1
Affiliations

Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

Qing Lei et al. Allergy. 2021 Feb.

Abstract

Background: The 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.

Measure: Utilizing 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.

Results: A 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.

Conclusion: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

Keywords: COVID-19; SARS-CoV-2; antibody dynamics; asymptomatic; neutralizing antibody.

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Conflict of interest statement

The authors declare no conflicts of interest. Dr Lei has nothing to disclose. Dr Li has nothing to disclose. Dr Hou has nothing to disclose. Dr Wang has nothing to disclose. Dr Ouyang has nothing to disclose. Dr Zhang has nothing to disclose. Dr Lai has nothing to disclose. Dr Banga Ndzouboukou has nothing to disclose. Dr Xu has nothing to disclose. Dr Zhang has nothing to disclose. Dr Chen has nothing to disclose. Dr Xue has nothing to disclose. Dr Lin has nothing to disclose. Dr Zheng has nothing to disclose. Dr Yao has nothing to disclose. Dr Wang has nothing to disclose. Dr Yu has nothing to disclose. Dr Jiang has nothing to disclose. Dr Zhang has nothing to disclose. Dr Qi has nothing to disclose. Dr Guo has nothing to disclose. Dr Huang has nothing to disclose. Dr Sun has nothing to disclose. Dr Tao has nothing to disclose. Dr Fan has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
The workflow of screening participants
FIGURE 2
FIGURE 2
Antibody responses to different proteins of SARS‐CoV‐2. Serum proteome microarray was used to probe IgM or IgG antibody against 20 proteins of SARS‐CoV‐2 in all samples collected from 63 healthy controls, 63 asymptomatic individuals, and 51 mild patients. The results were expressed as mean {log2 (Fluorescence intensity)} ± SD in different groups. A, Comparison of IgM responses to five proteins among three groups. B, Comparison of IgG responses to five proteins among three groups. Both analysis of variance (ANOVA) and post hoc test (SNK) were conducted to test difference in means among healthy controls, asymptomatics, and mild patients. ***P < .001, **P < .01, *P < .05, and ns indicating no significance
FIGURE 3
FIGURE 3
Dynamic changes of S1‐ and N‐specific IgM and IgG responses. Serum proteome microarray was used to probe antibody responses in the samples collected from 48 healthy individuals, 36 asymptomatic individuals, and 51 mild patients. The result of each serum sample was expressed as log2 (fluorescence intensity). 48 healthy controls and 36 asymptomatic infections having clear exposure history were plotted in sections according to the exposure time. 51 mild COVID‐19 patients with serial sera samples (n = 87) were segmented according to days after symptoms onset. The yellow, green and blue line showed the mean level of antibody responses in healthy controls, asymptomatic infections and mild patients, respectively. A, Dynamic changes of S1‐ and N‐specific IgM responses. B, Dynamic changes of S1‐ and N‐specific IgG responses
FIGURE 4
FIGURE 4
Neutralizing antibody responses and dynamics. The titer of neutralization antibody for each serum sample was expressed as the half‐maximal neutralizing titer (NT50), which was calculated by using nonlinear regression of SPSS. The results were shown as the medians of NT50 and interquartile ranges (IQRs) in different groups. A, Comparison of NT50 among healthy controls, asymptomatic infections and mild patients. B, Comparison of NT50 among different subgroups with that of healthy controls. C, Dynamic changes of NT50 for 48 healthy controls and 36 asymptomatic individuals over exposure time. D, Dynamic changes of NT50 for 51 mild COVID‐19 patients with the day after symptom onset. A loess 489 regression model was used to established the kinetics of neutralizing antibody by R. The lines show the mean value expected from a Loess 489 regression model, and the ribbons indicate the 95% confidence interval. Serum samples with NT50 below 1:10 are plotted at NT50 = 2
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