Establishment of a specimen panel for the decentralised technical evaluation of the sensitivity of 31 rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021

  1. Andreas Puyskens
  2. Eva Krause
  3. Janine Michel
  4. C Micha Nübling
  5. Heinrich Scheiblauer
  6. Daniel Bourquain
  7. Marica Grossegesse
  8. Roman Valusenko
  9. Victor M Corman
  10. Christian Drosten
  11. Katrin Zwirglmaier
  12. Roman Wölfel
  13. Constanze Lange
  14. Jan Kramer
  15. Johannes Friesen
  16. Ralf Ignatius
  17. Michael Müller
  18. Jonas Schmidt-Chanasit
  19. Petra Emmerich
  20. Lars Schaade
  21. Andreas Nitsche

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Abstract

The detection of SARS-CoV-2 with rapid diagnostic tests (RDT) has become an important tool to identify infected people and break infection chains. These RDT are usually based on antigen detection in a lateral flow approach.

Aim

We aimed to establish a comprehensive specimen panel for the decentralised technical evaluation of SARS-CoV-2 antigen rapid diagnostic tests.

Methods

While for PCR diagnostics the validation of a PCR assay is well established, there is no common validation strategy for antigen tests, including RDT. In this proof-of-principle study we present the establishment of a panel of 50 pooled clinical specimens that cover a SARS-CoV-2 concentration range from 1.1 × 10 9 to 420 genome copies per mL of specimen. The panel was used to evaluate 31 RDT in up to six laboratories.

Results

Our results show that there is considerable variation in the detection limits and the clinical sensitivity of different RDT. We show that the best RDT can be applied to reliably identify infectious individuals who present with SARS-CoV-2 loads down to 10 6 genome copies per mL of specimen. For the identification of infected individuals with SARS-CoV-2 loads corresponding to less than 10 6 genome copies per mL, only three RDT showed a clinical sensitivity of more than 60%.

Conclusions

Sensitive RDT can be applied to identify infectious individuals with high viral loads but not to identify all infected individuals.

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  1. Version published to 10.2807/1560-7917.es.2021.26.44.2100442
  2. ScreenIT

    SciScore for 10.1101/2021.05.11.21257021: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Confirmation of replication-competent SARS-CoV-2 was achieved by inoculation of VeroE6 cells with the respective pools.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Results obtained by visual examination of the test device by different laboratories were categorized as “positive” or “negative” and subjected to statistical analysis by using the GraphPad Prism software as indicated in the results section.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.05.11.21257021v1 on medRxiv