An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients

  1. Philippe Halfon
  2. Guillaume Penaranda
  3. Hacène Khiri
  4. Vincent Garcia
  5. Hortense Drouet
  6. Patrick Philibert
  7. Christina Psomas
  8. Marion Delord
  9. Frédérique Retornaz
  10. Caroline Charpin
  11. Thomas Gonzales
  12. Hervé Pegliasco
  13. Jérôme Allardet-Servent

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Abstract

We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.

Methods

From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.

Results

The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21–0.39), and 72 (95%CI 10–208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78–100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.

Conclusions

This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

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  1. Version published to 10.1371/journal.pone.0257817
  2. ScreenIT

    SciScore for 10.1101/2021.01.13.21249254: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: According to French regulations, the study was submitted to French ethics committee (CPP Sud-Méditerranée II) and registered as a reference methodology (MR-004) on the Health Data Hub French registering website platform (registration number: F20201028125903, https://www.health-data-hub.fr).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Calculations were performed using SAS V9.4 software (SAS Institute Inc.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    One of the major advantages of RAD in the effectiveness of surveillance of the outbreak beside shorter turnaround time and lowest cost is its speed of reporting more than its sensitivity27 Our study has some limitations. First, we do not assess RAD in the whole population of 43,399 patients but RAD was performed on a sample representative for TSO and Cts distribution among all RT-qPCR samples. Another limit is that calculations were performed on samples among whom 11% were positive for COVID-19; thus, the usefulness of RAD must be re- assessed according to the prevalence of COVID-19 by RT-qPCR. In summary, surveillance should prioritize sensibility, accessibility, frequency, and sample-to- answer time. However, based on the current understanding of sensitivity challenges, our study may alert the scientific community to the fact that extensive use and misinterpretation of RAD can lead to the misdiagnoses of COVID-19 patients due to its low predictive negative value. Negative results from an antigen test should be considered in context of the clinical observations, patient history, and epidemiological information and may need to be confirmed with a molecular test prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

    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.

    About SciScore

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  3. Version published to 10.1101/2021.01.13.21249254 on medRxiv