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SARS CoV-2 antibody assays measure antibodies against the viral nucleoprotein (NP) or spike protein. The study examined if testing of antibodies against both antigens increases the diagnostic sensitivity. Sera (N=98) from infected individuals were tested with ELISAs based on the NP, receptor-binding domain (RBD), or both proteins. The AUROCs were 0.958 (NP), 0.991 (RBD), and 0.992 (NP/RBD). The RBD- and NP/RBD-based ELISAs showed better performance than the NP-based assay. Simultaneous testing for antibodies against NP and RBD increased the number of true and false positives. If maximum diagnostic sensitivity is required, the NP/RBD-based ELISA is preferable. Otherwise, the RBD-based ELISA is sufficient. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04284-5.

SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS CoV-2 infection at later time points. To examine if the sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 56 sera obtained 6-8 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.6 % (95% confidence interval (CI) 85.1-98.9 %), 98.2 % (95% CI: 90.4-99.9 %) and 100 % (95% CI: 93.6-100 %). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 48.2 % (95% CI: 34.7-62.0 %) and 83.9 % (95% CI: 71.7-92.4 %). The nucleoprotein-based Roche and the glycoprotein-based Abbott RBD and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests (p=0.0001 to p=0.039). The N-based Abbott antibody test was less sensitive 6-8 months than 4-10 weeks after SARS-CoV-2 infection (p = 0.0002). The findings show that most SARS CoV-2 antibody assays correctly identified previous infection 6-8 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6-8 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost sensitivity over time.HighlightsMost antibody tests correctly identified SARS CoV-2 infection 6-8 months after infectionThe sensitivity of the antibody tests was 48.2-100 %The three tests with the highest sensitivity (94.6-100 %) were the N-based Roche and the RBD-based Abbott and Siemens assaysThe N-based Abbott IgG CMIA was significantly less sensitive 6-8 months than 4-10 weeks after infection (p = 0.0002)

Highlights • The sensitivity of commercial SARS CoV-2 IgG antibody tests was 64.4–93.2 %. • Positivity rate was higher with sera obtained 4 weeks than 2−3 weeks after RNA testing. • Antibody tests based on nucleoprotein and glycoprotein showed similar sensitivity. • Nucleoprotein- and glycoprotein-based antibody tests reacted with different sera., The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) has been followed by the rapid development of antibody tests. To assess the utility of the tests for clinical use and seroepidemiologic studies, we examined the sensitivity of commercial antibody tests from Roche, Abbott, Novatec, Virotech Siemens, Euroimmun, and Mediagnost in a prospective diagnostic study. The tests were evaluated with 73 sera from SARS CoV-2 RNA positive individuals with mild to moderate disease or asymptomatic infection. Sera were obtained at 2−3 weeks (N = 25) or > 4 weeks (N = 48) after symptom onset and viral RNA test. The overall sensitivity of the tests ranged from 64.4–93.2%. The most sensitive assays recognized 95.8–100 % of the sera obtained after 4 weeks or later. Sera drawn at 2−3 weeks were recognized with lower sensitivity indicating that the optimal time point for serologic testing is later than 3 weeks after onset of the disease. Nucleoprotein- and glycoproteinbased assays had similar sensitivity indicating that tests with both antigens are suitable for serological diagnostics. Breakdown of the test results showed that nucleoprotein- and glycoprotein-based tests of comparable sensitivity reacted with different sets of sera. The observation indicates that a combination of nucleoprotein- and glycoprotein-based tests would increase the percentage of positive results.