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

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: December 5, 2020.

Published Online: January 15, 2021. doi:10.1001/jamainternmed.2020.8876

Correction: This article was corrected on March 1, 2021, to fix Ms Yao’s name and academic degree in the byline.

Corresponding Author: Guillaume Butler-Laporte, MD, McGill University Health Centre, Royal Victoria Hospital, 1001 Decarie Blvd, Room E5.1820, Montréal, QC H4A 3J1, Canada (

Author Contributions: For the purposes of authorship, Drs McDonald and Lee contributed equally. Dr Butler-Laporte had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Butler-Laporte, McDonald, Lee.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Butler-Laporte, Yao, McDonald, Lee.

Critical revision of the manuscript for important intellectual content: Butler-Laporte, Lawandi, Schiller, Dendukuri, McDonald, Lee.

Statistical analysis: Butler-Laporte, Schiller, Yao, Dendukuri, Lee.

Administrative, technical, or material support: McDonald.

Supervision: Dendukuri, McDonald, Lee.

Conflict of Interest Disclosures: Dr Dendukuri reported receiving grants from the Canadian Institutes of Health Research for development of the Shiny app to perform bayesian diagnostic meta-analysis during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by a joint scholarship from the Fonds the Recherche du Québec–Santé and Québec’s Ministry of Health and Social Services (Dr Butler-Laporte), by the Intramural Research Program of the National Institutes of Health, Clinical Center (Dr Lawandi), by the Canadian Institutes of Health Research grant PJT-156039 (Dr Dendukuri), and by research salary funds from the Fonds de Recherche du Québec–Santé (Drs McDonald and Lee).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the National Institutes of Health.

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