In search for the SARS-CoV-2 protection correlate: A head-to-head comparison of two quantitative S1 assays in a group of pre-characterized oligo-/asymptomatic patients

Abstract

BackgroundQuantitative serological assays detecting response to SARS-CoV-2 infection are urgently needed to quantify immunity. This study analyzed the performance and correlation of two independent quantitative anti-S1 assays in oligo-/asymptomatic individuals from a previously characterized population-based cohort.MethodsA total of 362 samples included 108 from individuals who had viral RNA detected in pharyngeal swabs, 111 negative controls and 143 samples with positive serology but not confirmed by RT-PCR. Blood plasma was tested with quantitative assays Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG) (EI-S1-IgG-quant) and Roche Elecsys® Anti-SARS-CoV-2 CoV-2 S (Ro-RBD-Ig-quant), which were compared with each other and with confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript®cPass™. Results were analyzed using square roots R of coefficients of determination for association among continuous variables and non-parametric tests for paired comparisons.ResultsQuantitative anti-S1 serology correlated well with each other (96%/97% for true-positives and true-negatives, respectively). Antibody titers decreased over time (from <30 days to >240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true-positives and true-negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed a distinct separation between positive and negative values, and less non-specific reactivity compared with EI-S1-IgG-quant. Raw values (with 95% CI) ≥28.7 U/mL (22.6–36.4) for Ro-RBD-Ig-quant and ≥49.8 U/mL (43.4–57.1) for EI-S1-IgG-quant predicted virus neutralization >1:5 in 95% of cases.ConclusionsBoth quantitative anti-S1 assays, Ro-RBD-Ig-quant and EI-S1-IgG-quant, may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances in the future.Key pointsTwo quantitative anti-S1 assays showed similar performance and a high level of agreement with direct virus neutralization and surrogate neutralization tests, arguing for their utility in quantifying immune protection against SARS-CoV-2.