Abstract
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests is massive. The external validation of their performance is needed before use in clinical routine practice. Our study aims at assessing the analytical and clinical performance of two enzyme-linked immunosorbent assay tests detecting antibodies directed against the virus nucleocapsid protein: The NovaLisa SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) test (NovaTec) allowing a separate detection of each antibody and the Platelia SARS-CoV-2 Total Ab test (Bio-Rad) detecting total antibodies (IgM, IgA, and IgG). Two-hundred and eight coronavirus disease 2019 samples from 48 quantitative reverse transcription-polymerase chain reaction (RT-qPCR) confirmed patients were used to perform the sensitivity analysis. Non-SARS-CoV-2 sera (n = 79) with a potential cross-reaction to SARS-CoV-2 immunoassays were included in the specificity analysis. In addition, using receiver operator characteristic curves, adapted cut-off for improvement of the performances were proposed. The kinetics of these antibodies was also assessed over 8 weeks. Two weeks after the RT-qPCR positive detection, the NovaLisa test shows a sensitivity and specificity of 94.9% (95% confidence interval [CI]: 83.1%-98.6%) and 96.2% (95% CI: 89.4%-98.7%) for IgG, of 89.7% (95% CI: 76.4%-95.9%) and 98.7% (95% CI: 93.2%-98.8%) for IgA, and of 48.7% (95% CI: 33.9%-63.8%) and 98.7% (95% CI: 93.2%-99.8%) for IgM. With the Platelia system, the specificity and sensitivity were 97.4% (95% CI: 92.1%-99.7%) and 94.9% (95% CI: 87.7%-98.0%) for total antibodies using the adapted cut-offs. The NovaLisa and the Platelia tests have satisfactory analytical performances. The clinical performances are excellent for IgG, IgA, and total antibodies especially if the cut-off is optimized.
Keywords: COVID-19, ELISA; IgA; IgG; IgM; SARS-CoV-2; antibodies; kinetics.
【저자키워드】 antibodies, SARS-CoV-2, IgG, IgM, Kinetics, IgA, COVID-19, ELISA, 【초록키워드】 COVID-19, coronavirus disease, serological test, Coronavirus disease 2019, coronavirus, antibody, severe acute respiratory syndrome Coronavirus, virus, ELISA, immunoassay, sensitivity, specificity, enzyme-linked immunosorbent assay, RT-qPCR, Kinetics, Immunoglobulin G, Serological tests, Immunoglobulin, Sensitivity and specificity, nucleocapsid, sera, Patient, sensitivity analysis, respiratory, total antibody, immunoglobulin A, Quantitative, Analysis, external validation, immunoglobulin M, Chain Reaction, acute respiratory syndrome, 95% CI, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, reaction, 95% confidence interval, cut-off, positive, total antibodies, cut-offs, Bio-rad, enzyme-linked immunosorbent, Receiver operator characteristic, addition, eight, were used, Total, 【제목키워드】 SARS-CoV-2 IgG, IgM antibody,