Saliva as an alternative specimen to nasopharyngeal swabs for COVID-19 diagnosis: Review

Abstract

Almost 2 years ago, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered to be the causative agent of the disease COVID-19. Subsequently, SARS-CoV-2 has spread across the world infecting millions of people, resulting in the ongoing COVID-19 pandemic. The current ‘gold standard’ for COVID-19 diagnosis involves obtaining a nasopharyngeal swab (NPS) from the patient and testing for the presence of SARS-CoV-2 RNA in the specimen using real-time reverse transcription PCR (RT-qPCR). However, obtaining a NPS specimen is an uncomfortable and invasive procedure for the patient and is limited in its applicability to mass testing. Interest in saliva as an alternative diagnostic specimen is of increasing global research interest due to its malleability to mass testing, greater patient acceptability and overall ease of specimen collection. However, the current literature surrounding the sensitivity of saliva compared to NPS is conflicting. The aim of this review was to analyse the recent literature to assess the viability of saliva in COVID-19 diagnosis. We hypothesize that the discrepancies in the current literature are likely due to the variations in the saliva collection and processing protocols used between studies. The universal adaptation of an optimised protocol could alleviate these discrepancies and see saliva specimens be as sensitive, if not more, than NPS for COVID-19 diagnosis. Whilst saliva specimens are more complimentary to mass-testing, with the possibility of samples being collected from home, the RT-qPCR diagnostic process remains to be the rate-limiting step and therefore interest in salivary rapid antigen tests, which negate the wait-times of RT-qPCR with results available within 15–30 min, may be an answer to this.

Usability and performance of the MicroGEM Sal6830™, an RT-PCR saliva-based point-of-care platform to detect SARS-CoV-2 in primary healthcare settings with non-laboratory trained operators

“…The Sal6830™ viral capture chemistry only detects intact viral particles that are more likely to be infectious. Detection differences between the two sample types were recently reviewed in McPhillip and MacSharry (2022) [11] with saliva from the same patient shown to be positive when NPS is negative, and vice versa.…”

“…These results suggest that the Sal6830™ can be run safely and correctly by healthcare workers without training in laboratory practice and that the operation of the Sal6830™ platform is straightforward and intuitive. [11] with saliva from the same patient shown to be positive when NPS is negative, and vice versa.…”

Saliva as alternative to naso-oropharyngeal swab for SARS-CoV-2 detection by RT-qPCR: a multicenter cross-sectional diagnostic validation study

“…Substantial evidence already exists on the non-inferiority of saliva relative to NOS as a specimen for conventional RNA extraction-dependent RT-qPCR detection of SARS-CoV-2 7 , 8 . Compared to NOS as a testing sample, the use of saliva has several advantages 16 . In this alternative setup, compared to the number of staff that must be trained for adequate-quality NOS collection one patient at a time, fewer personnel needing less technical training are needed to facilitate simultaneous self-collection of saliva by multiple patients.…”

“…Arguably, a false sense of security may befall such patients if they were tested only by NOS RT-qPCR. We hypothesize that this subset of the population may be a greater clinical or public health risk than their swab-positive but saliva-negative counterparts, considering that SARS-CoV-2, in terms of anatomy and biomechanics, is more likely to be released from the host to the environment (through aerosolization and droplet formation) in saliva than in the nasopharynx 16 , 28 . With this consideration of perfect specificity and PPV in mind, we then analytically constructed a CRS wherein the criterion for a positive case is at least either a SARS-CoV-2-positive NOS, SE or SalivaDirect sample (virtually ensuring specificity and PPV of 100% since no volunteer can be considered false positive), and that for a negative case is SARS-CoV-2-negative NOS, SE and SalivaDirect samples.…”

Oral cavity manifestations in COVID-19 patients: A cross-sectional study

“…Accurate diagnosis is essential to control the outbreak and to propose measures related to the prevention and prognosis of infection. Saliva is a reliable, noninvasive specimen for diagnosing patients with suspected COVID-19 [7]. Furthermore, oral uid can be self-collected by subjects and can be easily managed, dramatically reducing the risk of viral transmission for healthcare workers [8].…”