Saliva as a Candidate for COVID-19 Diagnostic Testing: A Meta-Analysis

Abstract

Background: COVID-19 is a serious and potentially deadly disease. Early diagnosis of infected individuals will play an important role in stopping its further escalation. The present gold standard for sampling is the nasopharyngeal swab method. However, several recent papers suggested that saliva-based testing is a promising alternative that could simplify and accelerate COVID-19 diagnosis. Objectives: Our aim was to conduct a meta-analysis on the reliability and consistency of SARS-CoV-2 viral RNA detection in saliva specimens. Methods: We have reported our meta-analysis according to the Cochrane Handbook. We searched the Cochrane Library, Embase, Pubmed, Scopus, Web of Science and clinical trial registries for eligible studies published between 1 January and 25 April 2020. The number of positive tests and the total number of tests conducted were collected as raw data. The proportion of positive tests in the pooled data were calculated by score confidence-interval estimation with the Freeman-Tukey transformation. Heterogeneity was assessed using the I ² measure and the χ²-test. Results: The systematic search revealed 96 records after removal of duplicates. Twenty-six records were included for qualitative analysis and 5 records for quantitative synthesis. We found 91% (CI 80-99%) sensitivity for saliva tests and 98% (CI 89-100%) sensitivity for nasopharyngeal swab (NPS) tests in previously confirmed COVID-19 patients, with moderate heterogeneity among the studies. Additionally, we identified 18 registered, ongoing clinical trials of saliva-based tests for detection of the virus. Conclusion: Saliva tests offer a promising alternative to NPS for COVID-19 diagnosis. However, further diagnostic accuracy studies are needed to improve their specificity and sensitivity.

Keywords: COVID-19; SARS-CoV-2; coronavirus; diagnostic tests; meta-analysis; saliva; systematic review.

Figure 1

PRISMA flow diagram of the study selection process. Flow chart illustrating the selection process for identifying eligible records.

Figure 2

Forest plot analysis of SARS-CoV-2 detection sensitivity based on RT-qPCR analysis of saliva and nasopharyngeal swab (NPS) specimens from COVID-19 patients. (A) Proportion of positive saliva tests in the five studies included in the quantitative analysis, ranging from 0.78 to 1. The overall proportion in the pooled data is 0.91 (CI 0.80–0.99). The I² value (60.98%, p = 0.04) indicates a moderate level of statistical heterogeneity. (B) Proportion of positive NPS tests in the four studies included in the quantitative analysis, ranging from 0.91 to 1. The overall proportion in the pooled data is 0.98 (CI 0.89-1). The I² value (46.56%, p = 0.13) indicates a low level of statistical heterogeneity.