In Search of the SARS-CoV-2 Protection Correlate: Head-to-Head Comparison of Two Quantitative S1 Assays in Pre-characterized Oligo-/Asymptomatic Patients

Abstract

Background Quantitative serological assays detecting response to SARS-CoV-2 are needed to quantify immunity. This study analyzed the performance and correlation of two quantitative anti-S1 assays in oligo-/asymptomatic individuals from a population-based cohort. Methods In total, 362 plasma samples (108 with reverse transcription-polymerase chain reaction [RT-PCR]-positive pharyngeal swabs, 111 negative controls, and 143 with positive serology without confirmation by RT-PCR) were tested with quantitative assays (Euroimmun Anti-SARS-CoV-2 QuantiVac enzyme-linked immunosorbent assay [EI-S1-IgG-quant]) and Roche Elecsys ® Anti-SARS-CoV-2 S [Ro-RBD-Ig-quant]), which were compared with each other and confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript ® cPass™. Square roots R of coefficients of determination were calculated for continuous variables and non-parametric tests were used for paired comparisons. Results Quantitative anti-S1 serology correlated well with each other (true positives, 96%; true negatives, 97%). Antibody titers decreased over time (< 30 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 distinct separation between positives and negatives, and less non-specific reactivity versus EI-S1-IgG-quant. Raw values (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 NT > 1:5 in 95% of cases. Conclusions Our findings suggest both quantitative anti-S1 assays (EI-S1-IgG-quant and Ro-RBD-Ig-quant) may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances. However, although the mean antibody titers for both assays tended to decrease over time, a higher proportion of Ro-RBD-Ig-quant values remained positive after 240 days. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00475-x.

Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants

“…In the present study, results from the anti-RBD antibody test and CRNT positively correlated. This finding is consistent with previous reports ( 20 – 22 ), suggesting that the anti-RBD antibody test reflects protective immunity. In addition, CRNT and anti-RBD antibody testing successfully discriminated between symptomatic patients with COVID-19 patients in convalescence and suspected healthy individuals, suggesting that both tests are suitable for detecting SARS-CoV-2 infection.…”

Correlation between a quantitative anti‐SARS‐CoV‐2 IgG ELISA and neutralization activity

“…Similar performance was shown for the quantitative Elecsys assay, although this one provided a clearer positive‐negative separation and 3% less nonspecific reactivity. The results of Rubio‐Acero et al 17 correspond to and go beyond the correlation data of the present study.…”

“…Rubio‐Acero et al 17 were first to report the performance of two quantitative anti‐S1 assays, namely the QuantiVac ELISA (EUROIMMUN) and the Elecsys Anti‐SARS‐CoV‐2 S (Roche) using 362 samples. Among others, their results showed a high, statistically significant correlation of the QuantiVac ELISA with the primary semi‐quantitative EUROIMMUN Anti‐SARS‐CoV‐2 ELISA IgG ( r = 0.55), quantitative Elecsys assay ( r = 0.50), cPass surrogate neutralization test (GenScript; r = 0.41), and recom Line SARS‐CoV‐2 IgG MG‐RBD (Mikrogen; r = 0.46).…”

Antibodies against SARS-CoV-2 Time Course in Patients and Vaccinated Subjects: An Evaluation of the Harmonization of Two Different Methods

“…The good analytical characteristics of the two methods and the satisfactory correlation with the neutralization tests were previously evaluated and confirmed [12][13][14]. The concentrations were measured taking into consideration the previously determined reportable range of the respective methods [15].…”

“…The respective cut-offs were determined by the manufacturers on the basis of a specificity of 99.8%, and confirmed by independent studies [13,14].…”