Kinetics of the humoral immune response to SARS-CoV-2: comparative analytical performance of seven commercial serology tests

Abstract Background SARS-CoV-2 serology tests are clinically useful to document a prior SARS-CoV-2 infection in patients with no or inconclusive PCR results and suspected COVID-19 disease or sequelae. Data are urgently needed to select the assays with optimal sensitivity at acceptable specificity. Methods A comparative analysis of analytical sensitivity was performed of seven commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with PCR-confirmed SARS-CoV-2 infection, composed of 71 patients hospitalized for COVID-19 pneumonia and 64 healthcare workers with paucisymptomatic infections. The kinetics of IgA/IgM/IgG seroconversion to viral N-and S-protein epitopes were studied from 0 to 54 days after symptom onset. Specificity was verified on 57 pre-pandemic samples. Results Wantai SARS-COV-2 Ab ELISA and Orient Gene COVID-19 IgG/IgM Rapid Test achieved a superior overall sensitivity. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA also showed acceptable sensitivity (>95%) versus the consensus result of all assays from 10 days post symptom onset. Optimal specificity (>98%) was achieved only by Wantai SARS-COV-2 Ab ELISA, Elecsys Anti-SARS-CoV-2 assay and Innovita 2019-nCoV Ab rapid test. LIAISON SARS-CoV-2 S1/S2 IgG showed a significantly lower sensitivity as compared to all other assays. Lack of seroconversion by any test was seen in 1.4% of hospitalized and 4.7% of paucisymptomatic infections. Within 10 days from symptom onset, only the Wantai SARS-COV-2 Ab ELISA has acceptable sensitivity. Conclusions Wantai SARS-COV-2 Ab ELISA and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific screening of a SARS-CoV-2 infection from 10 days after symptom onset. Brief summary There is an urgent need for SARS-CoV-2 serology tests for the sensitive and specific detection of prior SARS-CoV-2 infection as a complementary diagnostic tool to molecular testing. Various commercial assays are becoming available but comparison of their relative performance is difficult unless they are head-to-head evaluated. Here we compared seven commercial assays on sera equally composed of mild and severe PCR-confirmed SARS-CoV-2 infections. Our analysis indicates a superior performance of the Wantai SARS-COV-2 ELISA for total antibodies to the S-RBD domain. Also, the Elecsys Anti-SARS-CoV-2 assay for total antibodies to the N-protein shows good performance for high-throughput screening.