1. Evaluation of High-Throughput SARS-CoV-2 Serological Assays in a Longitudinal Cohort of Patients with Mild COVID-19: Clinical Sensitivity, Specificity, and Association with Virus Neutralization Test
- Author
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Florence Morfin-Sherpa, Adèle Paul, Carole Langlois-Jacques, Sophie Trouillet-Assant, Virginie Pitiot, Constance D’Aubarède-Frieh, Bruno Pozzetto, Nicolas Guibert, David Goncalves, Jean-Baptiste Fassier, Nicole Fabien, François Gueyffier, Antonin Bal, Mary-Anne Trabaud, Amélie Massardier-Pilonchery, Bruno Lina, Muriel Rabilloud, Vanessa Escuret, and André Boibieux
- Subjects
Adult ,Male ,0301 basic medicine ,Coronavirus disease 2019 (COVID-19) ,Health-care workers ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Concordance ,030106 microbiology ,Clinical Biochemistry ,Virus Neutralization ,Antibodies, Viral ,Sensitivity and Specificity ,Article ,COVID-19 Serological Testing ,Serology ,Cohort Studies ,03 medical and health sciences ,Neutralization Tests ,Humans ,Medicine ,Longitudinal Studies ,Prospective Studies ,Neutralizing antibody ,Aged ,Biochemistry, medical ,biology ,SARS-CoV-2 ,business.industry ,Biochemistry (medical) ,COVID-19 ,Virus neutralization ,Antibodies, Neutralizing ,Virology ,Titer ,030104 developmental biology ,biology.protein ,Female ,Antibody ,business ,Serological assays - 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 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.
- Published
- 2021
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