A combination of N and S antigens with IgA and IgG measurement strengthens the accuracy of SARS-CoV-2 serodiagnostics.

Background The primary diagnosis of SARS-CoV-2 infection is based on the detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. Methods We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, MERS, and four low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA and IgM EIA results. Results The sensitivity of EIA for detecting immune response in COVID-19 patients (n=101) was 77 % in the acute phase and 100 % in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test (MNT) results. Conclusions The data indicate that a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of sera in IgG and IgA immunoglobulin classes provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.