Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis | Public Health | JAMA Internal Medicine | JAMA Network
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    1 Comment for this article
    Characterizing imperfect gold standards.
    Elizabeth Jenny-Avital |
    Coupling PCR tests (nasopharyngeal, saliva) with serial antibody titer might better characterize the performance characteristics of PCR viz false negative and false positive PCR tests....or teach us more about the imperfection of antibody tests.
    Original Investigation
    January 15, 2021

    Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Royal Victoria Hospital, Montréal, Québec, Canada
    • 2Department of Critical Care Medicine, National Institutes of Health, Clinical Center, Bethesda, Maryland
    • 3Centre for Outcomes Research, McGill University Health Centre, Montréal, Québec, Canada
    • 4Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Québec, Canada
    • 5Division of General Internal Medicine, Department of Medicine, McGill University, Montréal, Québec, Canada
    JAMA Intern Med. 2021;181(3):353-360. doi:10.1001/jamainternmed.2020.8876
    Key Points

    Question  Is saliva nucleic acid amplification testing (NAAT) comparable to nasopharyngeal NAAT, the current noninvasive criterion standard test for diagnosis of coronavirus disease 2019?

    Findings  In this systematic review and latent class meta-analysis adjusting for the imperfect reference standard, saliva NAAT had a similar sensitivity and specificity to that of nasopharyngeal NAAT.

    Meaning  Given the ease of use and good diagnostic performances, these findings suggest that saliva NAAT represents an attractive alternative to nasopharyngeal swab NAAT and may significantly bolster massive testing efforts.


    Importance  Nasopharyngeal swab nucleic acid amplification testing (NAAT) is the noninvasive criterion standard for diagnosis of coronavirus disease 2019 (COVID-19). However, it requires trained personnel, limiting its availability. Saliva NAAT represents an attractive alternative, but its diagnostic performance is unclear.

    Objective  To assess the diagnostic accuracy of saliva NAAT for COVID-19.

    Data Sources  In this systematic review, a search of the MEDLINE and medRxiv databases was conducted on August 29, 2020, to find studies of diagnostic test accuracy. The final meta-analysis was performed on November 17, 2020.

    Study Selection  Studies needed to provide enough data to measure salivary NAAT sensitivity and specificity compared with imperfect nasopharyngeal swab NAAT as a reference test. An imperfect reference test does not perfectly reflect the truth (ie, it can give false results). Studies were excluded if the sample contained fewer than 20 participants or was neither random nor consecutive. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the risk of bias.

    Data Extraction and Synthesis  Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed for the systematic review, with multiple authors involved at each stage of the review. To account for the imperfect reference test sensitivity, we used a bayesian latent class bivariate model for the meta-analysis.

    Main Outcomes and Measures  The primary outcome was pooled sensitivity and specificity. Two secondary analyses were performed: one restricted to peer-reviewed studies, and a post hoc analysis limited to ambulatory settings.

    Results  The search strategy yielded 385 references, and 16 unique studies were identified for quantitative synthesis. Eight peer-reviewed studies and 8 preprints were included in the meta-analyses (5922 unique patients). There was significant variability in patient selection, study design, and stage of illness at which patients were enrolled. Fifteen studies included ambulatory patients, and 9 exclusively enrolled from an outpatient population with mild or no symptoms. In the primary analysis, the saliva NAAT pooled sensitivity was 83.2% (95% credible interval [CrI], 74.7%-91.4%) and the pooled specificity was 99.2% (95% CrI, 98.2%-99.8%). The nasopharyngeal swab NAAT had a sensitivity of 84.8% (95% CrI, 76.8%-92.4%) and a specificity of 98.9% (95% CrI, 97.4%-99.8%). Results were similar in secondary analyses.

    Conclusions and Relevance  These results suggest that saliva NAAT diagnostic accuracy is similar to that of nasopharyngeal swab NAAT, especially in the ambulatory setting. These findings support larger-scale research on the use of saliva NAAT as an alternative to nasopharyngeal swabs.