Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection

  1. Yukari C. Manabe
  2. Carolyn Reuland
  3. Tong Yu
  4. Razvan Azamfirei
  5. Taylor Church
  6. Diane M. Brown
  7. Thelio T. Sewell
  8. Justin P. Hardick
  9. Paul W. Blair
  10. Chris D. Heaney
  11. Andrew Pekosz
  12. David L. Thomas

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Abstract

In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.07.20208520: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    We cultured all RT-PCR positive nasal-OP specimens on VeroE6 TMPRSS2 cells.
    VeroE6 TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)

    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:
    Our data underscore the limitations of salivary testing for SARS-CoV-2 and challenge of COVID-19 diagnostics. In contrast to the study of Wyllie et al., we generally detected less SARS-CoV-2 RNA in oral fluid compared to nasal-OP specimens in our outpatient cohort. Others also have reported testing discordance including lower sensitivity in saliva compared to NP samples.(2) Differences in salivary collection processes might explain the findings. Wyllie et al. collected expectorated samples in the morning, a process that might increase viral abundance by enrichment of deeper samples, especially in hospitalized patients with pneumonia.(3) In the present study, samples were self-collected in an ambulatory setting using a device that was optimized for detection of oral crevicular fluid antibodies. Oral fluid, useful for the detection of antibodies, may dilute the salivary sample and decrease its sensitivity for viral RNA detection. Many in vitro devices that are currently being tested for the direct detection of SARS-CoV-2 are proposing saliva including passive drool, spit, oral fluid, and sputum from clearing the throat. Not all salivary samples may be equivalent in terms of diagnostic utility and more data are needed to inform device manufacturers. Differences in the stage of infection may also factor since limited data suggest salivary tests have higher sensitivity in the first week of symptoms.(1, 4) The timing of collection, time after onset of symptoms, hospitalized vs outp...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.10.07.20208520 on medRxiv