Saliva Alternative to Upper Respiratory Swabs for SARS-CoV-2 Diagnosis

  1. Rachel L. Byrne
  2. Grant A. Kay
  3. Konstantina Kontogianni
  4. Ghaith Aljayyoussi
  5. Lottie Brown
  6. Andrea M. Collins
  7. Luis E. Cuevas
  8. Daniela M. Ferreira
  9. Alice J. Fraser
  10. Gala Garrod
  11. Helen Hill
  12. Grant L. Hughes
  13. Stefanie Menzies
  14. Elena Mitsi
  15. Sophie I. Owen
  16. Edward I. Patterson
  17. Christopher T. Williams
  18. Angela Hyder-Wright
  19. Emily R. Adams
  20. Ana I. Cubas-Atienzar

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  1. ScreenIT

    SciScore for 10.1101/2020.07.09.20149534: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Adults with signs and symptoms of suspected COVID-19 attending the Royal Liverpool University (RLUH) and Aintree University Hospitals (AUH) in Liverpool, UK were asked to provide specimens within 24 hours of informed consent given on the day of presentation (D0 ±1 day), figure 1 outlines the studies inclusion and exclusion criteria.
    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
    A SARS-CoV-2 isolate (REMRQ0001/human/2020/Liverpool) was propagated in Vero E6 cells (C1008; African green monkey kidney cells), as previously described (11).
    Vero E6
    suggested: RRID:CVCL_XD71)

    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:
    All saliva-positive, NT swab-negative samples in D2 (n=2) and D28 (n=1) reported low viral titre (<101 copies/ml) and are likely due to similar limitations outlined in the analytical sensitivity, a greater dilution factor of amies. It is important to note that these were from participants that had tested positive on D0 and thus likely to be true positive and support saliva to be more consistent for temporal sampling. This is in agreement with Wyllie et al., (2020) who reported that saliva had a greater sensitivity and was more likely to be constantly positive throughout the course of infection on a subset of COVID-19 hospitalised participants (n=29). All saliva-negative but NT swabs-positive were also low viral titre and may have resulted from the different processing time of the two specimens. As NT swabs underwent RNA extraction immediately, saliva samples were stored at −80°C prior to RNA extraction. Freeze-thawing can have a significant impact on the quality of RNA (Ji et al., 2017; Kuang et al., 2018) and it is possible the slightly lower viral loads in saliva were due to this freeze thaw event. Additionally, the lack of preservative media in saliva may reduce the viral detection due to RNA degradation. Sampling of saliva presents the opportunity to improve our approach to SARS-CoV-2 diagnostics. Saliva is easier to collect; it is non-invasive and much more accepted to the participant than NT swabs and is not reliant on the ability of the participant or staff to take a s...

    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 10.3201/eid2611.203283
  3. ScreenIT

    SciScore for 10.1101/2020.07.09.20149534: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementAdults with signs and symptoms of suspected COVID-19 attending the Royal Liverpool University (RLUH) and Aintree University Hospitals (AUH) in Liverpool, UK were asked to provide specimens within 24 hours of informe consent given on the day of presentation (D0 ±1 day), figure 1 outlines the studies inclusion and exclusion criteria.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableOf these 61 were female, 49 males.Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    A SARS-CoV-2 isolate (REMRQ0001/human/2020/Liverpool) was propagated in Vero E6 cells (C1008; African green monkey kidney cells), as previously described (11).
    Vero E6
    suggested: CVCL_XD71
    Software and Algorithms
    SentencesResources
    Acknowledgements We are grateful to all the participants recruited to the FASTER clinical research project, for taking the time in this pandemic situation to be involved in research.
    FASTER
    suggested: (FASTER, SCR_009045)

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

    • All saliva-positive, NT swab-negative samples in D2 (n=2) and D28 (n=1) reported low viral titre (<10 1 copies/ml) and are likely due to similar limitations outlined in the analytical sensitivity, a greater dilution factor of amies.
    • It is important to note that these were from participants that had tested positive on D0 and thus likely to be true positive and support saliva to be more consistent for temporal sampling.
    • This is in agreement with Wyllie et al., (2020) who reported that saliva had a greater sensitivity and was more likely to be constantly positive throughout the course of infection on a subset of COVID-19 hospitalised participants (n=29).
    • There will be numerous applications also in the UK for home sampling and the screening of children, who have previously been shown to reject swabbing.
    • As well as in research studies that require repeat sampling and due to the non-invasive nature of saliva will likely promote compliance by participants.

    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).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.09.20149534v1 on medRxiv