Rapid systematic review of the sensitivity of SARS-CoV-2 molecular testing on saliva compared to nasopharyngeal swabs

  1. E. Peeters
  2. S. Kaur Dhillon Ajit Singh
  3. J. Vandesompele
  4. P. Mestdagh
  5. V. Hutse
  6. M. Arbyn

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Abstract

Background

Nasopharyngeal sampling has been the standard collection method for COVID-19 testing. Due to its invasive nature and risk of contamination for health care workers who collect the sample, non-invasive and safe sampling methods like saliva, can be used alternatively.

Methods

A rapid systematic search was performed in PubMed and medRxiv, with the last retrieval on June 6 th , 2020. Studies were included if they compared saliva with nasopharyngeal sampling for the detection of SARS-CoV-2 RNA using the same RT-qPCR applied on both types of samples. The primary outcome of interest was the relative sensitivity of SARS-CoV-2 testing on saliva versus nasopharyngeal samples (used as the comparator test). A secondary outcome was the proportion of nasopharyngeal-positive patients that tested also positive on a saliva sample.

Results

Eight studies were included comprising 1070 saliva-nasopharyngeal sample pairs allowing assessment of the first outcome. The relative sensitivity of SARS-CoV-2 testing on saliva versus nasopharyngeal samples was 0.97 (95% CI=0.92-1.02). The second outcome incorporated patient data (n=257) from four other studies (n=97 patients) pooled with four studies from the first outcome (n=160 patients). This resulted in a pooled proportion of nasopharyngeal positive cases that was also positive on saliva of 86% (95% CI=77-93%).

Discussion

Saliva could potentially be considered as an alternative sampling method when compared to nasopharyngeal swabs. However, studies included in this review often were small and involved inclusion of subjects with insufficient information on clinical covariates. Most studies included patients who were symptomatic (78%, 911/1167). Therefore, additional and larger studies should be performed to verify the relative performance of saliva in the context of screening of asymptomatic populations and contact-tracing.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.05.20168716: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Systematic search: A rapid systematic search was performed using public bibliographic databases containing peer-reviewed and non-peer reviewed articles from PubMed and medRxiv, respectively.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Meta-analytical pooling using random effect models was performed in Stata (Stat version 16, StataCorp LLC, College Station, TX, USA).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Limitations of the systematic review: The retrieved literature focuses mainly on the virological sensitivity to detect a SARS-CoV-2 infection in different specimens. Additionally, there may have been implicit differences in method of collection, laboratories and equipment used that could not be investigated thoroughly due to limited information available. Besides, specificity to exclude an infection was rarely reported. Specificity is also an important parameter to consider particularly in situations where the pandemic is less prevalent and testing is used primarily for screening and contact-tracing purposes. The estimation of the virological accuracy of SARS-CoV-2 testing on saliva is only reliable when the RT-qPCR assays themselves are properly validated. This will further be evaluated in the VALCOR ("VALidation of SARS-CORona Virus-2 assays”) study which is currently ongoing in Belgium.34 The included studies comprised a heterogeneous case mix of subjects (from asymptomatic to patients with severe symptoms admitted to ICU). However, the sources of heterogeneity could not be assessed by lack of separate test results stratified by covariates. Furthermore, we encountered a lack of data for the second outcome with regard to the specifications of the RT-qPCR assays (i.e. manufacturer’s name and target genes) that have been used for the confirmation of on NP samples. Therefore, it might be possible that the RT-qPCR that has been used a priori on NP samples was different from the...

    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 10.1101/2020.08.05.20168716v1 on medRxiv