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

Abstract

Background 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 In contrast, saliva sampling can be self-administered. Methods 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 OR COVID19) AND (salivary OR saliva OR oral fluid)) NOT (review[Publication Type]) NOT (PrePrint[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. Findings A total of 377 studies were retrieved, of which 50 were eligible, reporting on 16,473 pairs of nasopharyngeal/oropharyngeal and saliva samples. Meta-analysis showed high concordance, 92.5% (95%CI: 89.5–94.7), across studies and pooled sensitivities of 86.5% (95%CI: 83.4–89.1) and 92.0% (95%CI: 89.1–94.2) from saliva and nasopharyngeal/oropharyngeal swabs respectively. Heterogeneity across studies was 72.0% for saliva and 85.0% for nasopharyngeal/oropharyngeal swabs. Interpretation Our meta-analysis strongly suggests that saliva could be used for frequent testing of COVID-19 patients and “en masse” screening of populations.

A Sensitive, Portable Microfluidic Device for SARS-CoV-2 Detection from Self-Collected Saliva

“…In addition, direct RT-qPCR of heated saliva samples without an RNA extraction step can shorten the assay time, use less sample (volume), and thus alleviate reagents shortage making it suitable for general screening [ 15 , 16 , 17 , 18 , 19 , 20 ]. Recently, detection of SARS-CoV-2 was compared between saliva and NP or OP swab samples [ 14 ]. This meta-analysis conclusively demonstrated that saliva was as valid as NP sampling for the detection of SARS-CoV-2 infection in both symptomatic and asymptomatic carriers.…”

“…It also provides comparable sensitivity to NP swabs [ 8 , 10 , 11 , 12 , 13 ]. Recently, the detection of SARS-CoV-2 was compared between saliva and NP or OP swab samples in a meta-analysis [ 14 ]. This conclusively demonstrated that the saliva was as valid as nasopharyngeal sampling for the detection of SARS-CoV-2 infection in both symptomatic and asymptomatic carriers.…”

SARS-CoV-2 Transmissibility Within Day Care Centers—Study Protocol of a Prospective Analysis of Outbreaks in Germany

“…Mouth and nose swabs and saliva samples are used because (a) both procedures are less invasive than nasopharyngeal or oropharyngeal swabs and are therefore more suitable for very young children (mouth swaps are dipped into medical glucose solution), and (b) they are an easier and more reliable method for self-testing. The combination of mouth and nose swabs and saliva samples has been shown to be of similar quality to a deep nasopharyngeal swab (22)(23)(24)(25)(26). The initial swabs are taken by trained staff during the first home visit.…”

One-Step RT-qPCR for Viral RNA Detection Using Digital Analysis

“…Along with the development of vaccines and treatments against virus, the diagnosis of viral infections using high-speed and accurate ribonucleic acid (RNA) detection assays is paramount, as various studies have reported ( Brown et al, 2021 ; Garg and Garg, 2021 ; Howe et al, 2021 ; Ibrahimi et al, 2021 ; Luethy and Johnson, 2021 ; Van Rijn and Boonstra, 2021 ; Yuan et al, 2021 ). For example, an integrated microfluidic system with reverse transcription-polymerase chain reaction (RT-PCR) has been developed for the rapid detection of influenza A viruses ( Shen et al, 2019 ).…”

“…The essential steps of isolating RNA from a viral sample and synthesizing complementary DNA (cDNA) through an RT reaction, then amplifying this cDNA using PCR, are routinely conducted manually ( Garg and Garg, 2021 ; Voon et al, 2021 ; Yuan et al, 2021 ). In general, a total reaction time of at least 4 h is required to isolate viral RNA from biological samples, synthesize cDNA, and perform PCR according to the manufacturer protocols ( Arevalo-Rodriguez et al, 2020 ; Ibrahimi et al, 2021 ). Moreover, conventional RT-qPCR analyses rely on 96- or 384-well plates, limiting high-throughput sample analysis in the case of mass infection.…”