Comparing immunoassays for SARS-Coronavirus-2 antibody detection in patients with and without laboratory-confirmed SARS-Coronavirus-2 infection.

Abstract

Background. Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. Methods. We cross-compared eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid(N)- or spike(S)-antigens in three cohorts consisting of 859 samples from 622 patients: (#1)EDI™-Novel-Coronavirus-COVID19, Epitope; (#2)RecomWell-SARS-CoV-2, Mikrogen; (#3)COVID19-ELISA, VirCell; (#4)Elecsys-Anti-SARS-CoV-2-N, Roche; (#5)LIAISON®-SARS-CoV-2-S1/S2, Diasorin; (#6)Anti-SARS-CoV-2-ELISA, EuroImmun; (#7)Elecsys-Anti-SARS-CoV-2-S, Roche; and (#8)LIAISON®-SARS-CoV-2-TrimericS, Diasorin. Results. In cross-sectional Cohort-1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional Cohort-2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with #7 and #8 revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/CoVID19 diagnosis and confirmed in the longitudinal Cohort-3 (281 sera from 74 CoVID19 patients), using assays #4, #6, #7 and #8. Sub-analysis of 20 (27%) initially seronegative Cohort-3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8-11 days and 14-18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6 and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. Conclusion. SARS-CoV-2 specific antibody assays show substantial agreement, but interpretation of qualitative and semi-quantitative results depends on the time elapsed post-diagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.