Diagnostic Performance of Rapid Antigen Testing for SARS-CoV-2: The COVid-19 AntiGen (COVAG) study

  1. Christoph Wertenauer
  2. Geovana Brenner Michael
  3. Alexander Dressel
  4. Caroline Pfeifer
  5. Ulrike Hauser
  6. Eberhard Wieland
  7. Christian Mayer
  8. Caren Mutschmann
  9. Martin Roskos
  10. Hans-Jörg Wertenauer
  11. Angela P. Moissl
  12. Stefan Lorkowski
  13. Winfried März

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Abstract

Rapid diagnostic testing for SARS-Cov-2 antigens is used to combat the ongoing pandemic. In this study we aimed to compare two RDTs, the SD Biosensor Q SARS-CoV-2 Rapid Antigen Test (Roche) and the Panbio COVID-19 Ag Rapid Test (Abbott), against rRT-PCR.

Methods

We included 2,215 all-comers at a diagnostic center between February 1 and March 31, 2021. rRT-PCR-positive samples were examined for SARS-CoV-2 variants.

Findings

Three hundred and thirty eight participants (15%) were rRT-PCR-positive for SARS-CoV-2. The sensitivities of Roche-RDT and Abbott-RDT were 60.4 and 56.8% ( P < 0.0001) and specificities 99.7% and 99.8% ( P = 0.076). Sensitivity inversely correlated with rRT-PCR-Ct values. The RDTs had higher sensitivities in individuals referred by treating physicians (79.5%, 78.7%) than in those referred by health departments (49.5%, 44.3%) or tested for other reasons (50%, 45.8%), in persons without any comorbidities (74.4%, 71%) compared to those with comorbidities (38.2%, 34.4%), in individuals with COVID-19 symptoms (75.2%, 74.3%) compared to those without (31.9%, 23.3%), and in the absence of SARS-CoV-2 variants (87.7%, 84%) compared to Alpha variant carriers (77.1%, 72.3%). If 10,000 symptomatic individuals are tested of which 500 are truly positive, the RDTs would generate 38 false-positive and 124 false-negative results. If 10,000 asymptomatic individuals are tested, including 50 true positives, 18 false-positives and 34 false-negatives would be generated.

Interpretation

The sensitivities of the two RDTs for asymptomatic SARS-CoV-2 carriers are unsatisfactory. Their widespread use may not be effective in the ongoing SARS-CoV-2 pandemic. The virus genotype influences the sensitivity of the two RDTs. RDTs should be evaluated for different SARS-CoV-2 variants.

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  1. Version published to 10.3389/fmed.2022.774550
  2. ScreenIT

    SciScore for 10.1101/2021.08.04.21261609: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written and informed consent.
    IRB: The study was approved by Ethics Committee II (Mannheim) of the University of Heidelberg (reference number 2020-417MF) and the German Institute for Drugs and Medical Devices.
    Sex as a biological variableDifferences in continuous variables between men and women were examined by two-sided t-tests; the chi-squared test was used for categorical variables (Table 1).
    RandomizationWe randomly assigned the study population to three sampling groups according to the time sequence of collecting the nasopharyngeal swabs (group 1: rRT-PCR, RDT-Roche, RDT-Abbott; group 2: RDT-Roche, RDT-Abbott, rRT-PCR; and group 3: RDT-Abbott, rRT-PCR, RDT-Roche).
    BlindingThis ensured that the performers of the RDTs were unaware of the rRT-PCR-results.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In addition to collecting the nasopharyngeal swabs for rRT-PCR testing, we collected two completely independent swab specimens to run two commercially available and widely used Ag-RDTs from Abbott Diagnostics (Abbott Panbio TM COVID-19 Ag Rapid Test, Abbott Rapid Diagnostics Jena GmbH, Jena, Germany, www.abbott.com/poct) and Roche Diagnostics (Roche-SD Biosensor SARS-CoV-2 Rapid Antigen Test, identical to SD BIOSENSOR Standard Q COVID-19 Ag, www.sdbiosensor.com; Roche Diagnostics; Mannheim, Germany, www.roche.com).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Samples in which both N501Y and H69/V70 were absent may have contained variants other than Alpha, Beta, or Gamma or the wild-type.
    Gamma
    suggested: (GAMMA, RRID:SCR_009484)
    The analyses were carried out using R v4.0.2 (http://www.r-project.org).
    http://www.r-project.org
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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:
    Limitations: We applied rRT-PCR as the reference method to detect SARS-CoV-2 infection. Despite being considered the gold standard, this technique has the limitation that the detection of SARS-CoV-2 RNA in patient samples does not indicate the presence or shedding of viable virus with replicative capacity or whether the tested individual is contagious at the time of the test 12,26. Although the presence of viral RNA proven by rRT-PCR does not automatically equate to infectiousness, a significant correlation between the Ct value (reflecting viral load) and subsequent virus cultivation has been observed. Samples with Ct values between 13 and 17 have a culture positivity rate of 100%, which declines gradually to 12% when Ct values of 33 are analysed. No viral growth occurs at Ct values ≥34, suggesting that patients with these values do not excrete infectious viral particles 17. Therefore, if infectivity rather than a positive rRT-PCR test were considered the reference for RDTs, our results would stand more in favour of RDT testing. However, a direct conversion of Ct values or a positive RDT to contagiousness has not yet been established. Ct values can hardly be compared across studies, and the correlation between viral load and the risk of transmission from a positive case is still not entirely clear 13,27, with a variety of circumstances, such as the individual’s behaviour, the type and duration of contact, the environment, and the implementation of transmission-reducing measur...

    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 10.1101/2021.08.04.21261609v1 on medRxiv