Association between SARS-CoV-2 Neutralizing Antibodies and Commercial Serological Assays. (7th October 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Clinical chemistry. Volume 66:Number 12(2020)
• Page Start: 1538
• Page End: 1547
• Publication Date: 2020-10-07
• Subjects: Serology -- neutralizing antibodies -- COVID-19 -- SARS-CoV-2; Clinical chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Biochimie -- Périodiques; Diagnostics biologiques -- Périodiques; Biochemistry; Clinical chemistry; Pharmaceutical chemistry; Biochemistry; Laboratory Techniques and Procedures; Klinische chemie; Periodicals; 616.075605
• DOI: 10.1093/clinchem/hvaa211
• Languages: English
• ISSNs: 0009-9147

Abstract

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.