Assessment of S1, S2 and NCP-specific IgM, IgA, and IgG antibody kinetics in acute SARS-CoV-2 infection by a microarray and twelve other immunoassays.

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute SARS-CoV-2 infection. Three-hundred-fifty-four blood samples longitudinally obtained from 81 IgG seroconverting CoVID-19 patients were quantified for spike (S)1, S2, and nucleocapsid protein (NCP)- specific IgM, IgA, IgG, and total Ig antibodies using a microarray, eleven different ELISAs/CLIAs, and one rapid test by seven manufacturers. The assays' specificity was assessed in 130 non-CoVID19 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, respectively. 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.