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Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation

Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test...

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Autores principales: Einhauser, Sebastian, Peterhoff, David, Niller, Hans Helmut, Beileke, Stephanie, Günther, Felix, Steininger, Philipp, Burkhardt, Ralph, Heid, Iris M., Pfahlberg, Annette B., Überla, Klaus, Gefeller, Olaf, Wagner, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534748/
https://www.ncbi.nlm.nih.gov/pubmed/34679541
http://dx.doi.org/10.3390/diagnostics11101843
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author Einhauser, Sebastian
Peterhoff, David
Niller, Hans Helmut
Beileke, Stephanie
Günther, Felix
Steininger, Philipp
Burkhardt, Ralph
Heid, Iris M.
Pfahlberg, Annette B.
Überla, Klaus
Gefeller, Olaf
Wagner, Ralf
author_facet Einhauser, Sebastian
Peterhoff, David
Niller, Hans Helmut
Beileke, Stephanie
Günther, Felix
Steininger, Philipp
Burkhardt, Ralph
Heid, Iris M.
Pfahlberg, Annette B.
Überla, Klaus
Gefeller, Olaf
Wagner, Ralf
author_sort Einhauser, Sebastian
collection PubMed
description Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a “test establishment setting” to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup (n = 856) of the larger population based TiKoCo-19 cohort (n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn’t provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn’t provide satisfactory quantitative correlations.
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spelling pubmed-85347482021-10-23 Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation Einhauser, Sebastian Peterhoff, David Niller, Hans Helmut Beileke, Stephanie Günther, Felix Steininger, Philipp Burkhardt, Ralph Heid, Iris M. Pfahlberg, Annette B. Überla, Klaus Gefeller, Olaf Wagner, Ralf Diagnostics (Basel) Article Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a “test establishment setting” to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup (n = 856) of the larger population based TiKoCo-19 cohort (n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn’t provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn’t provide satisfactory quantitative correlations. MDPI 2021-10-06 /pmc/articles/PMC8534748/ /pubmed/34679541 http://dx.doi.org/10.3390/diagnostics11101843 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Einhauser, Sebastian
Peterhoff, David
Niller, Hans Helmut
Beileke, Stephanie
Günther, Felix
Steininger, Philipp
Burkhardt, Ralph
Heid, Iris M.
Pfahlberg, Annette B.
Überla, Klaus
Gefeller, Olaf
Wagner, Ralf
Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title_full Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title_fullStr Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title_full_unstemmed Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title_short Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
title_sort spectrum bias and individual strengths of sars-cov-2 serological tests—a population-based evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534748/
https://www.ncbi.nlm.nih.gov/pubmed/34679541
http://dx.doi.org/10.3390/diagnostics11101843
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