Performance of Various Lateral Flow SARS-CoV-2 Antigen Self Testing Methods in Healthcare Workers: a Multicenter Study

  1. V.F. Zwart
  2. N. van der Moeren
  3. J.J.J.M. Stohr
  4. M.C.W. Feltkamp
  5. R.G. Bentvelsen
  6. B.M.W. Diederen
  7. A.C. de Laat
  8. E.M. Mascini
  9. I.G.P. Schilders
  10. H.T.M. Vlassak
  11. H.F.L. Wertheim
  12. J.L.A.N. Murk
  13. J.A.J.W. Kluytmans
  14. W. van den Bijllaardt

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Abstract

Introduction

Rapid antigen detection tests (RDT) are suitable for large-scale testing for SARS-CoV-2 among the population and recent studies have shown that self-testing with RDT in the general population is feasible and yields acceptable sensitivities with high specificity. We aimed to determine the accuracy of two different RDT’s, with two different sample collection methods for one of the RDT’s among healthcare workers (HCW). Secondary objectives were to determine the accuracy of RDT using a viral load cut-off as proxy of infectiousness and to identify predictors for a false negative RDT.

Methods

Centers that participated were secondary care hospitals, academic teaching hospitals, and long-term care facilities. All HCW that met inclusion criteria were asked to perform a RDT self-test next to a regular SARS-CoV-2 nucleic acid amplification test (NAAT). Three study groups were created. Study group 1; Veritor(tm) System, Becton Dickinson, Franklin Lakes, USA (BD-RDT) with combined oropharyngeal - mid-turbinate nasal sampling, group 2; BD-RDT with mid-turbinate nasal sampling only and group 3; SD Biosensor SARS-CoV-2 Rapid Antigen Test, Roche, Basel, Switzerland (Roche-RDT) with combined oropharyngeal - mid-turbinate nasal sampling. RDT accuracy was calculated using NAAT as reference standard. For samples processed in the cobas ® 6800/8800 platform (Roche Diagnostics, Basel, Switzerland), established cycle threshold values (Ct-values) could be converted into viral loads. A viral load cut-off of ≥5.2 log10 SARS-CoV-2 E gene copies/ml was used as proxy of infectiousness. Logistic regression analysis was performed to identify predictors for a false negative RDT.

Results

In total, 7,196 HCW were included. Calculated sensitivities were 61.5% (95%CI 56.6%-66.3%), 50.3% (95%CI 42.8%-57.7%) and 74.2% (95%CI 66.4%-80.9%) for study groups 1, 2 and 3, respectively. After application of a viral load cut-off as a proxy for infectiousness for samples processed in the cobas ® 6800/8800 platform sensitivities increased to 82.2% (95%CI 76.6-86.9%), 61.9% (95%CI 48.8%-73.9%) and 90.2% (95%CI 76.9%-97.3%) for group 1, group 2 and group 3, respectively. Multivariable regression analysis showed that use of Roche-RDT (p <0.01), combined oropharyngeal - mid-turbinate nasal sampling (p <0.05) and the presence of COVID-19 like symptoms at the time of testing (p <0.01) significantly reduced the likeliness of a false-negative RDT result.

Conclusion

SARS-CoV-2 RDT has proven able to identify infectious individuals, especially when upper respiratory specimen is collected through combined oropharyngeal - mid-turbinate sampling. Reliability of self-testing with RDT among HCW seems to depend on the type of RDT, the sampling method and the presence of COVID-19 like symptoms at the time of testing.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.28.22269783: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Every HCW aged 18 years or older and able to understand the written instructions in Dutch, was asked to participate and provide verbal informed consent.
    IRB: The study protocol was reviewed by the Dutch ‘Medical research Ethics Committees United’ (MEC-U) and was judged to be beyond the scope of the Dutch medical scientific research act (WMO) (MEC-U subject: W20.250).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisSubsequent to inclusion of the required number of participants in study group 1 in accordance with the power calculation, the participating centres were switched to either study group 2 or 3.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Calculations and statistical analysis were performed using SPSS version 24 (IBM Corp. Armonk NY, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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: We detected the following sentences addressing limitations in the study:
    This study shows that RDT’s can be used as self-tests but that there are certain limitations considering the sensitivity. In general, RDT’s perform well in individuals with a high SARS-CoV-2 viral load which is usually present in the pre-symptomatic and early symptomatic phase – the first 5-7 days – of COVID-19 (11,12). Multiple validation studies for RDT have been published in which a higher sensitivity is observed at low Ct-values (high viral loads) for different RDT brands and different qRT-PCR platforms (1-3, 13-17). It is a point of discussion above which viral load and therefore below which Ct-value people are likely to be infectious. After infection with SARS-CoV-2, viral RNA can be detected by qRT-PCR during a long time, even if the infected person is no longer infectious (18, 19). Taking the viral load of SARS-CoV-2 as a proxy for infectiousness – by determining the viral load cut-off above which 95% of qRT-PCR positive samples had a positive virus culture – and extrapolating it to a cut-off Ct-value for comparable PCR platforms is the most feasible and closest to the true rate of infectiousness (6, 10, 20). When adjusted for infectiousness for all qRT-PCR results of samples processed in the cobas® 6800/8800 the sensitivity clearly increased for each group. The sensitivities were 82,2%, 61,9% and 90,2% for study group 1, study group 2 and study group 3, respectively. The increased sensitivity after adjustment for infectiousness is in line with previous studies (6, 10...

    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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  2. Version published to 10.1101/2022.01.28.22269783v1 on medRxiv