Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2

Abstract

IMPORTANCE Nasopharyngeal swab nucleic acid amplification testing (NAAT) is the noninvasive criterion standard for diagnosis of coronavirus disease 2019 . 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 MEASURESThe 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. RESULTSThe 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 RELEVANCEThese 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.

Risk of dispersion or aerosol generation and infection transmission with nasopharyngeal and oropharyngeal swabs for detection of COVID-19: a systematic review

“…Finally, recent evidence regarding salivary nucleic acid amplification testing has supported comparable diagnostic accuracy, with a pooled sensitivity of 83.2% (95% CIs 74.7% to 91.4%) and specificity of 99.2% (95% CI 98.2% to 99.8%), compared with nasopharyngeal swab testing (84.8% (95% CI 76.8% to 92.4%) and 98.9% (95% CI 97.4% to 99.8%), respectively). 19 While demonstrating comparable yield, salivary testing was associated with lower costs. 20 Coupled with increased ease of testing, reduced invasiveness and likely reduced occupational exposure risk, salivary testing may be a viable alternative to nasopharyngeal or oropharyngeal swab testing.…”

“…In late December 2019, a novel coronavirus, subsequently referred to by the World Health Organization (WHO) as SARS-CoV-2, was identified as the cause of atypical pneumonia cases detected in Wuhan, China. 1 Since then, SARS-CoV-2-related disease (named COVID- 19) has emerged as a global pandemic. 2 In 1 year, SARS-CoV-2 has spread to over 200 countries, infecting over 100 million individuals, and causing over 2 million deaths internationally.…”

Sensitivity of the Molecular Test in Saliva for Detection of COVID-19 in Pediatric Patients With Concurrent Conditions

“…The values of sensitivity and specificity were estimated using the results of the NP/OP swap as reference standard (19)(20)(21) as described by Linnet and coworkers (22). The overall percent agreement was calculated following FDA recommendations (27).…”

“…As alternative measures of agreement between results of saliva and NP/OP swabs, the overall percent agreement and κ statistics were estimated (27,28). Results of NP/OP swabs were used as reference standard for calculation of sensitivity and specificity (19)(20)(21). To analyze the potential association of clinical variables with the concordance rate between saliva and NP/OP swab, we used χ 2 test to compare proportions and calculate risk.…”

“…The use of early morning saliva collected just after waking, before eating, drinking or tooth brushing has also been explored (4-6, 8, 9), but in a hospitalization context, this requirement would prevent sampling at reception or before emergency procedures. Reported concordance rates between upper respiratory tract swabs and saliva have been highly variable (53-100%) (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Currently there is no consensus on the use of different saliva sampling techniques, detection kits, RNA extraction methods, and the optimal time window for saliva collection after symptoms onset (21).…”