Abstract
Background: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19.
Methods: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers.
Results: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3% (78.1-96.1), and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC < 0.76).
Conclusions: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.
Keywords: COVID-19; SARS-CoV-2; health-care workers; serological assays; virus neutralization.
【저자키워드】 COVID-19, SARS-CoV-2, serological assays, Virus neutralization, Health-care workers, 【초록키워드】 neutralizing antibody, IgG, IgM, S protein, Neutralizing antibodies, Antibody Response, RT-PCR, healthcare worker, Receptor binding domain, serum, sensitivity, specificity, Serological tests, Concordance, Serological assay, RBD, serological assays, IgA, clinical, sera, virus neutralization test, neutralization test, Virus neutralization, serological, disease, Antibody titers, mild patients, Neutralizing titer, association, ROC Curve, clinical sensitivity, AUC, except for, best, can not, neutralizing antibody titers, DiaSorin, clinical specificity, specimen, Siemens, VNT, health-care, lowest, Course, greater, detect, collected, evaluated, functional, the RBD, the S protein, subset, Area, Total, ranged, mild patient, with COVID-19, 【제목키워드】 Test, clinical, longitudinal,