Screening for SARS-CoV-2 by RT-PCR: saliva or nasopharyngeal swab? Systematic review and meta-analysis

Abstract

Diagnosis of COVID-19 in symptomatic patients and screening of populations for SARS-CoV-2 infection require access to straightforward, low-cost and high-throughput testing. The recommended nasopharyngeal swab tests are limited by the need of trained professionals and specific consumables and this procedure is poorly accepted as a screening method. The use of alternative validated samples such as saliva is thus much awaited.In order to compare saliva and nasopharyngeal/oropharyngeal samples for the detection of SARS-CoV-2, we designed a meta-analysis searching in PubMed up to December 29th, 2020 with the key words “((SARS-CoV-2 OR COVID-19) AND (saliva OR oral fluid)) NOT (review[Publication Type]” applying the following criteria: records published in peer reviewed scientific journals, in English, with at least 15 nasopharyngeal/orapharyngeal swabs and saliva paired samples tested by RT-PCR, studies with available raw data including numbers of positive and negative tests with the two sampling methods. For all studies, concordance and sensitivity were calculated and then pooled in a random-effects model.A total of 318 studies were retrieved, of which 49 were eligible, reporting on 16,272 pairs of nasopharyngeal/oropharyngeal and saliva samples. Meta-analysis showed high concordance, 92.6% (95%CI: 89.6-94.8), across studies and pooled sensitivities of 86.7% (95%CI: 83.5-89.3) and 92.2 (95%CI: 89.4-94.4) from saliva and nasopharyngeal/oropharyngeal swabs respectively. Heterogeneity across studies was 80.0% for saliva and 84.0% for nasopharyngeal/oropharyngeal swabs.Our meta-analysis strongly suggests that saliva could be used for frequent testing of COVID-19 patients and “en masse” screening of populations.Three published meta-analysis comparing SARS-CoV-2 loads in paired saliva and nasopharyngeal samples included only 4, 5 and 16 studies up to December 29th, 2020. We thus searched additional studies in PubMed with the key words “((SARS-CoV-2 OR COVID-19) AND (saliva OR oral fluid)) NOT (review[Publication Type])” applying the following criteria: records published in peer reviewed scientific journals, in English, with at least 15 saliva and nasopharyngeal/orapharyngeal paired samples tested by RT-PCR, studies with available raw data including numbers of positive and negative tests with the two sampling methods.Forty-nine published studies were eligible, reporting on 16,272 pairs of saliva and nasopharyngeal/oropharyngeal samples. Our unprecedented meta-analysis showed high concordance (92.6%) across studies and pooled sensitivities of 86.7% and 92.2% from saliva and nasopharyngeal/oropharyngeal swabs respectively.Sensitivity of SARS-CoV-2 RT-PCR detection in saliva samples is above the 80% sensitivity cut-off recommended by health regulatory authorities. Our meta-analysis validates the use of saliva sample for mass screening to combat the COVID-19 pandemic.