Association between neutralizing antibodies to SARS-CoV-2 and commercial serological assays

Tang, M. S.; Case, J. B.; Franks, C. E.; Chen, R. E.; Anderson, N. W.; Henderson, J. P.; Diamond, M. S.; Gronowski, A. M.; Farnsworth, C. W.

doi:10.1101/2020.07.01.182220

bioRxiv · 10.1101/2020.07.01.182220

Association between neutralizing antibodies to SARS-CoV-2 and commercial serological assays

Tang, M. S.·Case, J. B.·Franks, C. E.·Chen, R. E.·Anderson, N. W.·Henderson, J. P.·Diamond, M. S.·Gronowski, A. M.·Farnsworth, C. W.

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Abstract

Introduction Commercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies.Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes.Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms.Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Tang, M. S., Case, J. B., Franks, C. E., Chen, R. E., Anderson, N. W., Henderson, J. P., Diamond, M. S., Gronowski, A. M., Farnsworth, C. W.. 2020-07-02. Association between neutralizing antibodies to SARS-CoV-2 and commercial serological assays. https://doi.org/10.1101/2020.07.01.182220

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