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

Rubio-Acero, R.; Castelletti, N.; Fingerle, V.; Olbich, L.; Bakuli, A.; Woelfel, R.; Girl, P.; Mueller, K.; Jochum, S.; Strobl, M.; Hoelscher, M.; Wieser, A.; team, KoCo19 study

Background Quantitative 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 antiS1 assays in oligo-/asymptomatic individuals from a previously characterized population-based cohort. Methods A 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(R) 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(R)cPassTM. Results were analyzed using square roots R of coefficients of determination for association among continuous variables and non-parametric tests for paired comparisons. Results Quantitative 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. Conclusions: Both 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.