Sensitivity of Rapid Antigen Testing and RT-PCR Performed on Nasopharyngeal Swabs versus Saliva Samples in COVID-19 Hospitalized Patients: Results of a Prospective Comparative Trial (RESTART)

  1. Antonios Kritikos
  2. Giorgia Caruana
  3. René Brouillet
  4. John-Paul Miroz
  5. Samia Abed-Maillard
  6. Geraldine Stieger
  7. Onya Opota
  8. Antony Croxatto
  9. Peter Vollenweider
  10. Pierre-Alexandre Bart
  11. Jean-Daniel Chiche
  12. Gilbert Greub

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Abstract

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients.

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  1. Version published to 10.3390/microorganisms9091910
  2. ScreenIT

    SciScore for 10.1101/2021.04.09.21255105: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Inclusion criteria were a) positive NP RT-PCR for SARS-CoV-2 in the previous 5 days, b) age >18 years-old and c) informed consent acquisition by the patient or the next of a kin for patients incapable to provide informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    On the other hand, this study has a few limitations as well. Its monocentric nature and limited sample size require our results to be confirmed by larger prospective trials. Our patients were initially diagnosed with NP swab RT-PCR that might have induced a bias towards subsequent NP swabs being more often positive versus other samples. Hospitalized patients may have altered saliva production or composition (25) that could influence saliva based diagnostic strategies or even explain the differences observed in salivary RT-PCR performances among severely and mildly ill COVID-19 patients. We chose to use a validated and easy to use non-invasive saliva collection procedure (5). It is possible that other methods of saliva collection (such as throat washing for example) would have improved diagnostic yield and should therefore be tested in other comparative trials. In conclusion, NP swab RT-PCR was the most sensitive method to diagnose SARS-CoV-2 infection in moderately to critically ill hospitalized patients. Salivary RT-PCR could be used as an alternative non-invasive method if NP swabs are contraindicated, particularly for patients presenting early in the course of the disease. VTM induced dilution effect can impact diagnostic performance of RAT.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04839094CompletedDry Versus Wet Nasopharyngeal Rapid Test for the Detection o…

    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 10.1101/2021.04.09.21255105 on medRxiv