Saliva as an Alternative to Nasopharyngeal Swab Specimen for Reverse-transcription Polymerase Chain Reaction (RT-PCR) Diagnosis of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis

Abstract

Objectives. To assess the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) of saliva specimens compared to RT-PCR of nasopharyngeal swabs (NPS) in the diagnosis of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.

Methods. A database search was conducted in MEDLINE, the Cochrane COVID Study Register, the COVID-19 Living Evidence Database, medRxiv, and bioRxiv for published articles and preprints dated between 1 January and 26 December 2020 of studies on the diagnostic accuracy of saliva RT-PCR compared to nasopharyngeal swab (NPS) RT-PCR. Studies included cross-sectional, cohort, and case-control designs. Risk of bias assessment was done using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity estimates were determined using a bivariate random-effects model. Subgroup analysis was done based on patients’ diagnostic and symptom status, healthcare setting, and collection method. Certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for all pooled analyses.

Results. Fifty-one studies with 16,476 paired specimens were included. Overall pooled analysis showed that saliva RT-PCR had 84% (95% confidence interval 80-88%) sensitivity and 96% (95% CI 94-98%) specificity compared to NPS RT-PCR. No significant difference in sensitivity or specificity was found between subgroups. Substantial heterogeneity (>70%) was noted for all analyses. The certainty of evidence for the overall study was moderate for both sensitivity and specificity.

Conclusion. Using saliva RT-PCR has comparable sensitivity and specificity to NPS in diagnosing SARS-CoV-2 infection regardless of patient diagnostic or symptom status, healthcare setting, or collection method. It may be used as an alternative specimen for diagnosis.