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

• Published in: Infectious diseases and therapy Vol. 10; no. 3; pp. 1505 - 1518
• Main Authors: Rubio-Acero, Raquel, Castelletti, Noemi, Fingerle, Volker, Olbrich, Laura, Bakuli, Abhishek, Wölfel, Roman, Girl, Philipp, Müller, Katharina, Jochum, Simon, Strobl, Matthias, Hoelscher, Michael, Wieser, Andreas
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01-09-2021; Springer; Springer Nature B.V
• Subjects: Asymptomatic; Comparative analysis; COVID-19; Electronic components industry; Enzyme-linked immunosorbent assay; Enzymes; Ethylenediaminetetraacetic acid; Health aspects; Immunoglobulin G; Infectious Diseases; Internal Medicine; Medicine; Medicine & Public Health; Neutralization; Original Research; Pharmaceutical industry; Serology; Severe acute respiratory syndrome coronavirus 2; United States; Germany; COVID-19; Direct virus neutralization assay S1; SARS-CoV-2; Quantitative serology
• ISSN: 2193-8229; 2193-6382
• DOI: 10.1007/s40121-021-00475-x

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.