Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2
Laura Olbrich, Noemi Castelletti, Yannik Schälte, Mercè Garí, Peter Pütz, Abhishek Bakuli, Michael Pritsch, Inge Kroidl, Elmar Saathoff, Jessica Michelle Guggenbüehl Noller, Volker Fingerle, Ronan Le Gleut, Leonard Gilberg, Isabel Brand, Philine Falk, Alisa Markgraf, Flora Deák, Friedrich Riess, Maximilian N. Diefenbach, Tabea M. Eser, Franz Weinauer, Silke Martin, Ernst-Markus Quenzel, Marc Becker, Jürgen Durner, Philipp Girl, Katharina Müller, Katja Radon, Christiane Fuchs, Roman Wölfel, Jan Hasenauer, Michael Höelscher, Andreas Wieser, on behalf of the KoCo19-Study Group
Abstract
A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives ( n =193), true-negatives ( n =1091), and specimens of unknown status ( n =5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen- recom Line-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer’s cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer’s/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen- recom Line-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPass TM or recom Line-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.