TY - JOUR
T1 - In Search of the SARS-CoV-2 Protection Correlate
T2 - Head-to-Head Comparison of Two Quantitative S1 Assays in Pre-characterized Oligo-/Asymptomatic Patients
AU - the KoCo19 study team
AU - Rubio-Acero, Raquel
AU - Castelletti, Noemi
AU - Fingerle, Volker
AU - Olbrich, Laura
AU - Bakuli, Abhishek
AU - Wölfel, Roman
AU - Girl, Philipp
AU - Müller, Katharina
AU - Jochum, Simon
AU - Strobl, Matthias
AU - Hoelscher, Michael
AU - Wieser, Andreas
AU - Alamoudi, Emad
AU - Anderson, Jared
AU - Baldassare, Valeria
AU - Baumann, Maximilian
AU - Behlen, Marieke
AU - Becker, Marc
AU - Beyerl, Jessica
AU - Böhnlein, Rebecca
AU - Brand, Isabel
AU - Brauer, Anna
AU - Britz, Vera
AU - Bruger, Jan
AU - Caroli, Friedrich
AU - Contento, Lorenzo
AU - Czwienzek, Alina
AU - Deák, Flora
AU - Dech, Emma
AU - Dech, Laura
AU - Diefenbach, Maximillian N.
AU - Diekmannshemke, Jana
AU - Do, Anna
AU - Dobler, Gerhard
AU - Eberle, Ute
AU - Durner, Juergen
AU - Eberle, Ute
AU - Eckstein, Judith
AU - Eser, Tabea
AU - Falk, Philine
AU - Frese, Jonathan
AU - Fischer, Stefanie
AU - Forster, Felix
AU - Frahnow, Turid
AU - Frese, Jonathan
AU - Fröschl, Günter
AU - Fuchs, Christiane
AU - Laxy, Michael
AU - Theis, Fabian
AU - Zeggini, Eleftheria
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - COVID-19
KW - Direct virus neutralization assay S1
KW - Quantitative serology
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85108338230&partnerID=8YFLogxK
U2 - 10.1007/s40121-021-00475-x
DO - 10.1007/s40121-021-00475-x
M3 - Article
AN - SCOPUS:85108338230
SN - 2193-8229
VL - 10
SP - 1505
EP - 1518
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 3
ER -
