无症状 COVID-19 感染者体内针对 SARS-CoV-2 的抗体动态变化。
Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections.
机构信息
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
出版信息
Allergy. 2021 Feb;76(2):551-561. doi: 10.1111/all.14622. Epub 2020 Oct 26.
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.
背景
由于核酸检测（NAT）的敏感性不完善，无症状 COVID-19 感染者一直被忽视。全球范围内了解无症状感染者的体液免疫将为开发血清学检测、提高早期识别能力以及实施更合理的大流行控制策略提供科学知识。
方法
我们利用 NAT 和商业试剂盒广泛筛查了 11766 名流行病学疑似感染者，并在入组时检测到并招募了 63 名无症状感染者。将 63 名健康个体和 51 名无任何既往疾病的轻症患者作为对照。使用 SARS-CoV-2 蛋白质组微阵列进一步探测血清 IgM 和 IgG 谱，并使用假型病毒中和测定系统检测中和抗体。分析了暴露时间或症状出现与抗体动力学的关系。
结果
NAT 和 IgM 抗体血清学联合检测发现，63 名无症状感染者中共有 55.5%的总感染率，与单独 NAT 相比，检测灵敏度显著提高（19%）。血清蛋白质组微阵列分析表明，无症状感染者主要产生针对 SARS-CoV-2 20 种蛋白中的 S1 和 N 蛋白的 IgM 和 IgG 抗体。与强烈和持续的 N 特异性抗体不同，无症状感染者早在暴露后第 7 天就出现了 S1 特异性 IgM 反应，在第 17 天至第 25 天达到峰值，然后在两个月内消失，可能成为早期诊断的生物标志物。11.8%（6/51）轻症患者和 38.1%（24/63）无症状感染者未产生中和抗体。特别是，无症状感染者的中和抗体在两个月内逐渐消失。
结论
我们的发现可能对无症状 COVID-19 感染的定义、诊断、血清学调查、公共卫生和免疫接种策略具有重要意义。
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