Association between SARS-CoV-2 Neutralizing Antibodies and Commercial Serological Assays

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 66; no. 12; pp. 1538 - 1547
• Main Authors: Tang, Mei San, Case, James Brett, Franks, Caroline E, Chen, Rita E, Anderson, Neil W, Henderson, Jeffrey P, Diamond, Michael S, Gronowski, Ann M, Farnsworth, Christopher W
• Format: Journal Article
• Language: English
• Published: Washington Oxford University Press 01.12.2020; American Association for Clinical Chemistry, Inc
• Subjects: Analysis; Antibodies; Antibody response; Antigens; Assaying; Control; Coronaviruses; COVID-19; Epidemics; Immunoglobulin G; Methods; Neutralization; Neutralizing; Patients; Qualitative analysis; Serodiagnosis; Serology; Severe acute respiratory syndrome coronavirus 2; United States; Viral antigens; Viral diseases; Viral proteins; United States; COVID-19; neutralizing antibodies; SARS-CoV-2; Serology
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/hvaa211

Abstract Background 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 are limited published data associating the results from commercial assays with neutralizing antibodies. Methods Sixty-six specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys Anti-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) and 56% (30–80); Abbott was 96% (88–99) and 69% (44–86); and EUROIMMUN was 91% (80–96) and 81% (57–93) for distinguishing neutralizing antibodies. Patients who were intubated, had cardiac injury, or acute kidney injury from COVID-19 infection had higher neutralizing titers relative to those with mild symptoms. Conclusions 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.