Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis

Abstract

RT-qPCR utilising upper respiratory swabs are the diagnostic gold standard for SARS-CoV-2 despite reported low sensitivity and limited scale up due to global shortages. Saliva is a non-invasive, equipment independent alternative to swabs. We collected 145 paired saliva and nasal/throat (NT) swabs at diagnosis (day 0) and repeated on day 2 and day 7 dependent on inpatient care and day 28 for study follow up. Laboratory cultured virus was used to determine the analytical sensitivity of spiked saliva and swabs containing amies preservation media. Self-collected saliva samples were found to be consistent, and in some cases superior when compared to healthcare worker collected NT swabs from COVID-19 suspected participants. We report for the first time the analytical limit of detection of 10-2 and 100 pfu/ml for saliva and swabs respectively. Saliva is a easily self-collected, highly sensitive specimen for the detection of SARS-CoV-2.

Relative Sensitivity of Saliva and Upper Airway Swabs for Initial Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Ambulatory Patients

“…One hundred forty-nine papers were considered for inclusion; of these, 19 studies comprising 21 cohorts met inclusion criteria ( Supplemental Figure S1 ). A brief summary of the studies included in this review may be found in Table 1 , and a brief discussion of each paper (including the results used in this review) is presented in the Supplemental Appendix S1 3 , 4 , 5 , 6 , 7 , 8 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 . Twelve of the included cohorts involved 100 or more patients.…”

“…The third study, which was thought to have alow risk of spectrum bias, found saliva to be less sensitive than NP swab 8 . Importantly, 5 of the 7 cohorts in which saliva provided greater sensitivity were thought to be associated with a high risk of spectrum bias with respect to initial diagnostic testing of a community population 21 , 22 , 25 , 27 , 29 . Of 10 cohorts that included patients who had previously tested positive for SARS-CoV2, or included hospitalized patients, four showed higher sensitivity for saliva specimens 21 , 25 , 27 , 29 , two showed sensitivity identical to that for NP swabs 23 , 28 , and four showed higher sensitivity for NP or MT swabs 17 , 18 , 20 , 26 .…”

“…Of 10 cohorts that included patients who had previously tested positive for SARS-CoV2, or included hospitalized patients, four showed higher sensitivity for saliva specimens 21 , 25 , 27 , 29 , two showed sensitivity identical to that for NP swabs 23 , 28 , and four showed higher sensitivity for NP or MT swabs 17 , 18 , 20 , 26 . A single study of asymptomatic health care workers identified four positives from saliva samples and none using NP swabs 22 . In contrast, 7 of 9 cohorts believed to have a low risk of spectrum bias with respect to diagnosis demonstrated higher sensitivity for NP swabs than for saliva specimens 3 , 4 , 5 , 6 , 8 , 19 .…”

“…Three cohorts included in this review dealt with testing of asymptomatic individuals. 19 , 22 Data from two of the three cohorts suggest superiority for saliva, although only one, a contact-tracing cohort, includes more than five positive subjects. Another study by Wyllie et al 2 , which did not meet the formal inclusion critria for this systematic review, arrived at the same conclusion.…”

“…Equivocal results and assay failures were not used in the calculation of sensitivity, nor in the construction of the CRS for each study. Confidence limits for sensitivity were computed using Newcombe’s efficient score method 16 as implemented in the Vassarstats Clinical Calculator 1 ( http://vassarstats.net/ )( Table 1 ) 3 , 4 , 5 , 6 , 7 , 8 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 . Criteria for performing a formal meta-analysis were as follows: 1) studies used the same amplification technology [such as RT-PCR]; 2) studies used the same upper airway sample site (AN, MT and NP could be included together, but not admixed with studies based on OP samples; 3) studies enrolled a similar patient mix (e.g., symptomatic, asymptomatic, hospitalized) and similar clinical environment (drive-through/ community health center or hospital).…”