Abstract
Background: Throughout the coronavirus disease 2019 (Covid-19) pandemic numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have been approved through Emergency Use Authorization and require further evaluation of sensitivity and specificity in clinical laboratory settings prior to implementation.
Methods: We included 1733 samples from 375 PCR-confirmed SARS-CoV-2-positive individuals of the North Zealand Covid-19 Cohort in an 8-month period. We investigated diagnostic sensitivity and specificity against consensus and PCR and interassay agreement over time for 5 SARS-CoV-2 immunoassays [Roche-nucleocapsid (NC)-total, Roche-receptor binding domain (RBD)-total, Siemens-RBD-IgG, Siemens-RBD-total, Thermo Fisher Scientific (TFS)-RBD-IgG] commercially available on automated platforms and 2 ELISA assays (TFS-RBD-total, Wantai-RBD-total).
Results: Early interassay discrepancy in up to 49% of samples decreased steadily during the first 18 days. By day 18, all assays had reached a plateau between 82.3% and 90.5% seropositivity compared to PCR. Assays ranked by closest agreement with the consensus model beyond day 18 (sensitivity/specificity against consensus) were as follows: Roche-RBD-total, 99.8%/100.0%; Wantai-RBD-total, 99.8%/99.7%; Roche-NC-total, 97.8%/100.0%; Siemens-RBD-total, 98.0%/98.7%; TFS-RBD-total, 96.9%/99.7%; TFS-RBD-IgG, 91.5%/100.0%; and Siemens-RBD-IgG, 94.6%/89.9%. We found that 7.8% of PCR-positive patients remained seronegative in all assays throughout the study.
Conclusions: All included assays had sensitivities against consensus >90% past day 18. For the current recommended use of antibody assays to detect former, undocumented Covid-19, our data suggest the use of total antibody assays rather than IgG-specific assays due to higher long-term sensitivity. Finally, a nonresponding subpopulation of 7.8% in our cohort with persistent seronegative results raises concern of a possible substantial number of people with continued low protection following natural SARS-CoV-2 infection.
Keywords: Covid-19; SARS-CoV-2 antibodies; cohort; comparison study; immunoassays; longitudinal study; serological testing.
【저자키워드】 COVID-19, immunoassays, Cohort, SARS-CoV-2 antibodies, longitudinal study, comparison study, serological testing., 【초록키워드】 coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, coronavirus, pandemic, SARS-COV-2 infection, diagnostic, Emergency use authorization, Laboratory, immunoassays, immunoassay, sensitivity, Cohort, SARS-CoV-2 antibodies, PCR, Serological testing, Sensitivity and specificity, longitudinal study, diagnostic sensitivity, implementation, Seropositivity, automated, antibody assay, respiratory, Roche, platform, seronegative, ELISA assay, Antibody assays, Emergency, clinical laboratory, Consensus, acute respiratory syndrome, acute respiratory syndrome coronavirus, PCR-confirmed, acute respiratory syndrome coronavirus 2, North, sensitivities, binding domain, discrepancy, authorization, plateau, ELISA assays, Thermo Fisher Scientific, Siemens, subpopulation, raise, detect, investigated, remained, approved, reached, PCR-positive patient, SARS-CoV-2-positive individual, 【제목키워드】 SARS-CoV-2, North,