Evaluation of Three SARS CoV-2 IgG Antibody Assays and Correlation with Neutralizing Antibodies

Rychert, Jenna; Couturier, Marc Roger; Elgort, Marc; Lozier, Bucky Ken; La’ulu, Sonia; Genzen, Jonathan R; Straseski, Joely A; Delgado, Julio C; Slev, Patricia R

BACKGROUND: As serologic assays for SARS-CoV-2 become more widely utilized, it is important to understand their performance characteristics and correlation with neutralizing antibodies. We evaluated three commonly used SARS-CoV-2 IgG assays (Abbott, DiaSorin and EUROIMMUN) for clinical sensitivity, specificity, and correlation with neutralizing antibodies and then compared antibody kinetics during the acute phase of infection. METHODS: Three panels of samples were tested on every assay. Sensitivity was assessed using a panel of 35 specimens serially collected from 7 RT-PCR-confirmed COVID-19 patients. Specificity was determined using 100 sera samples collected in 2018 from healthy individuals prior to the outbreak. Analytical specificity was determined using a panel of 37 samples from individuals with respiratory illnesses other than COVID-19. RESULTS: Clinical sensitivity was 91.43% (95% CI 76.94%-98.20%) for Abbott, and 88.57% (95% CI 73.26%-96.80%) for both DiaSorin and EUROIMMUN. Clinical specificity was 99.00% (95% CI 94.55%-99.97%) for Abbott and DiaSorin and 94.00% (95% CI 87.40%-97.77%) for EUROIMMUN. The IgG assays demonstrated good qualitative agreement (minimum of 94%) and good correlation between the quantitative result for each combination of assays (r2≥0.90). The neutralizing antibody response did not necessarily follow the same temporal kinetics as the IgG response and did not necessarily correlate with IgG values. CONCLUSION: The three IgG antibody assays demonstrated comparable performance characteristics. Importantly, a qualitative positive IgG result obtained with any of the assays was associated with the presence of neutralizing antibodies; however, neutralizing antibody concentrations did not correlate well with signal to cutoff ratios.