In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Three hundred fifty-four blood samples longitudinally obtained from 81 IgG-seroconverting progressed coronavirus disease 2019 (CoVID-19) patients were quantified for spike 1 (S1), S2, and nucleocapsid protein (NCP)-specific IgM, IgA, IgG, and total Ig antibodies using a microarray, 11 different enzyme-linked immunosorbent assays (ELISAs)/chemiluminescence immunoassays (CLIAs), and 1 rapid test by seven manufacturers. The assays’ specificity was assessed in 130 non-CoVID-19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th day post-symptom onset, all patients developed IgG responses against S1, S2, and NCP. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.

中文翻译：

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通过微阵列和十二种其他免疫测定方法评估急性SARS-CoV-2感染中S1，S2-和NCP特异性IgM，IgA和IgG抗体的动力学

在这项研究中，我们全面分析了急性重症急性呼吸综合征冠状病毒2（SARS-CoV-2）住院患者中不同免疫球蛋白的多特异性抗体动力学。从81例IgG血清学转换进展性冠状病毒病2019（CoVID-19）患者纵向获得的354份血液样本中，对棘突1（S1），S2和核衣壳蛋白（NCP）特异的IgM，IgA，IgG和使用微阵列检测总共Ig抗体，11种不同的酶联免疫吸附测定（ELISA）/化学发光免疫测定（CLIA），以及7家制造商进行的1种快速检测。在130名非CoVID-19肺炎患者中评估了测定的特异性。使用微阵列，NCP特异性IgA和IgG抗体在急性CoVID-19期间持续显示出比S1和S2特异性更高的检测率。但是，S1特异性IgG抗体达到了更高的峰值。直到症状发作后第26天，所有患者均产生针对S1，S2和NCP的IgG反应。尽管ELISA / CLIA的检测率通常与微阵列的检测率相似，但与靶抗原相对应，但在所有测试中敏感性和特异性均不同。值得注意的是，具有更严重CoVID-19的患者显示出更高的IgG和IgA水平，但是这种差异主要是通过S1特异性免疫分析法观察到的。在下呼吸道SARS-CoV-2水平高的患者中，我们观察到高的IgG检测率和总Ig免疫测定，尤其是当气管抽吸物中的病毒浓度随时间下降时，S1特异性IgG抗体特别上升。总而言之，我们的研究表明，急性SARS-CoV-2感染期间商业免疫分析的敏感性差异仅部分与靶抗原有关。重要的是，我们的数据表明，较早检测到NCP特异性IgA和IgG抗体，而重症患者则出现更高的S1特异性IgA抗体水平。