Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: a Systematic Review and Meta-analysis

  1. Rose A. Lee
  2. Joshua C. Herigon
  3. Andrea Benedetti
  4. Nira R. Pollock
  5. Claudia M. Denkinger

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Abstract

Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity.

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  1. Version published to 10.1128/jcm.02881-20
  2. ScreenIT

    SciScore for 10.1101/2020.11.12.20230748: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationCross-sectional, case-control, and cohort studies and randomized controlled trials were included independent of number of specimens tested.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy, information sources, and eligibility criteria: We performed a comprehensive search of the following databases (Pubmed/MEDLINE and Google Scholar) as well as the preprint servers medRxiv and bioRxiv to identify relevant studies from January 1st, 2020 until October 1st, 2020.
    Pubmed/MEDLINE
    suggested: None
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    All analyses and graphs were performed using Stata 15.1 (StataCorp, Texas) and GraphPad 8.5 (Prism, SanDiego).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Example search method employed in systematic review and meta-analysis: The following strategy was used in Medline/Pubmed to identify articles providing a quantitative evaluation of diagnostic tests by specimen type: (“COVID-19 diagnostic testing”[MeSH Supplementary Concept] AND “Coronavirus Infection” [MeSH Major Topic] AND [“saliva”[MeSH Major Topic] OR “nose” [MeSH Major Topic] OR “nasal” “oropharynx” [MeSH Major Topic] OR “oropharyngeal” OR “oral” OR “nasopharynx” [MeSH Major Topic] OR “nasopharyngeal”].
    Medline/Pubmed
    suggested: None
    MeSH
    suggested: (MeSH, RRID:SCR_004750)

    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:
    While we assess aggregate data from different studies to gain insight into these variables, a limitation of this meta-analysis is that true comparison is precluded in the absence of head-to-head studies. Furthermore, while there are trends we observe in our subgroup analyses, these findings may be population-related and should be interpreted with caution. Timing of sampling from symptom onset was also quite variable (collection occurred within days to weeks in some studies), and was inconsistently reported, which likely had a major impact on diagnostic performance given decreasing viral load over time. Head-to-head studies are urgently needed of flocked vs unflocked swabs (and specialized vs unspecialized swabs for MT collection), collected at different times in disease and with different sampling methods, and also in important subpopulations (e.g. children), to resolve the persistent uncertainty. We note that the reporting quality of studies was low, STARD guidelines (74) were not consistently followed, and study bias was considered moderate to high on QUADAS 2. Lastly, in this study we chose to report the % positive alternative-specimen, % positive comparator-specimen, and % dual positives instead of the positive percent agreement (PPA). This decision was motivated by our presumption regarding the low rate of false-positives using NAAT, and the potential for an alternative to yield more positive results than the comparator NP, which would otherwise not be considered. In sum...

    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2020.11.12.20230748 on medRxiv