Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2 (original) (raw)

, M. Gaeddert, L. Köppel, L. E. Brümmer, C. Gottschalk, I.B. Miranda, P. Schnitzler, H.G. Kräusslich, A.K. Lindner, O. Nikolai, F.P. Mockenhaupt, J. Seybold, V.M. Corman, C. Drosten, N.R. Pollock, A.I. Cubas-Atienzar, K. Kontogianni, A. Collins, A. H. Wright, B. Knorr, A. Welker, M. de Vos, J.A. Sacks, E.R. Adams, C.M. Denkinger, for the study team

doi: https://doi.org/10.1101/2020.10.01.20203836

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Abstract

Background Reliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection and ease-of-use of three antigen-detecting, rapid POC tests (Ag-RDT) for SARS-CoV-2.

Methods This prospective, multi-centre diagnostic accuracy study recruited participants suspected to have SARS-CoV-2 in Germany and the UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical RT-PCR and one for Ag-RDT). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptoms onset, etc. In addition, limited verification of the analytical limit-of-detection (LOD) was determined. To understand the usability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed.

Results Between April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76×6% (95% Confidence Interval (CI) 62×8-86×4) sensitive and 99×3% (CI 98×6-99×6) specific. A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC. Bioeasy and Coris showed specificity of 93×1% (CI 91×0%-94×8%) and 95×8% (CI 93×4%-97×4%), respectively, not meeting the predefined target of ≥98%.

Conclusion There is large variability in performance of Ag-RDT with SD Biosensor showing promise. Given the usability at POC, this test is likely to have impact despite imperfect sensitivity; however further research and modelling are needed.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

German Clinical Trial Registry DRKS00021220

Clinical Protocols

https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00021220

Funding Statement

The study was supported by FIND, Heidelberg University Hospital and Charite University Hospital internal funds. Pfizer funded the clinical team in Liverpool, UK. The external funders of the study had no role in study design, data collection, or data analysis. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study protocol was approved by the ethical review committee at the University Hospital Heidelberg for the study sites in Heidelberg and Berlin (Registration number S-180/2020), and by the NHS review board, IRAS number 282147, for the study in Liverpool, UK. Each participant provided written informed consent.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

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Footnotes

Data Availability

The data will be available upon request.

Copyright

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.