Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2

  1. Laura Olbrich
  2. Noemi Castelletti
  3. Yannik Schälte
  4. Mercè Garí
  5. Peter Pütz
  6. Abhishek Bakuli
  7. Michael Pritsch
  8. Inge Kroidl
  9. Elmar Saathoff
  10. Jessica Michelle Guggenbuehl Noller
  11. Volker Fingerle
  12. Ronan Le Gleut
  13. Leonard Gilberg
  14. Isabel Brand
  15. Philine Falk
  16. Alisa Markgraf
  17. Flora Deák
  18. Friedrich Riess
  19. Max Diefenbach
  20. Tabea Eser
  21. Franz Weinauer
  22. Silke Martin
  23. Ernst-Markus Quenzel
  24. Marc Becker
  25. Jürgen Durner
  26. Philipp Girl
  27. Katharina Müller
  28. Katja Radon
  29. Christiane Fuchs
  30. Roman Wölfel
  31. Jan Hasenauer
  32. Michael Hoelscher
  33. Andreas Wieser
  34. on behalf of the KoCo19-Study Group

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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.

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  1. Version published to 10.1099/jgv.0.001653 on Access Microbiology
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    SciScore for 10.1101/2021.01.13.21249735: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Ethics Commission of the Faculty of Medicine at LMU Munich (20-275-V) and the protocol is available online (www.koco19.de).17 Laboratory Assays: All described analyses were performed using EDTA-plasma samples (appendix pp.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    It may also be preferable to have a more sensitive cut-off for a primary test and confirm the positives with a highly-specific secondary test system in low prevalence settings.(17) Our study has several of limitations. Firstly, the samples are mostly derived from subjects with mild to no symptoms and therefore conclusions drawn here might best apply to an epidemiological rather than a diagnostic approach. Further evaluation using specimens from severely ill subjects or from high-prevalence settings will need to be conducted and compared to the enclosed results. Secondly, the dataset used to estimate optimised cut-offs and performance of the tests is not an unbiased random sample, as all were sampled in the city of Munich, Germany. It cannot be ruled out that blood donors are generally healthier than the general population. Furthermore, not all confirmatory tests were performed on all samples; only a subset, namely those with positive results in at least one primary test and a dedicated negative/positive cohort, were tested using these systems. Finally, we did not have information on underlying health conditions known to increase the quantity of polyclonal antibodies. In conclusion, our study provides a head-to-head cross-comparison of tests and can be used as a resource to enable the refinement of testing-strategies for individual and public-health use. We also investigated the correlations of the different test systems in-depth, considering confounders such as seasonality an...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2021.01.13.21249735 on medRxiv