Evaluation of saliva as a complementary technique to the diagnosis of COVID-19: a systematic review

Abstract

Background Infectious disease coronavirus 2019 (COVID-19) is caused by the SARS-CoV-2 virus, and it mainly affects the upper respiratory tract. The gold standard for its diagnosis is real-time reverse transcription polymerase chain reaction (RT-qPCR) performed on a nasopharyngeal swab. In contrast, testing saliva has significant advantages as a diagnostic method. Material and Methods We searched for articles evaluating saliva as a diagnostic method for COVID-19 on the PUBMED/MEDLINE, WEB OF SCIENCE, COCHRANE, and SCIELO platforms. We initially found 233 articles and 20 were selected for inclusion following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol: 18 cross-sectional studies and 2 case reports, including 8 from America, 8 from Asia, and 4 from Europe. The studies evaluated the presence of viral RNA, IgG, IgM, and IgA in samples of unstimulated saliva from adults with confirmed or suspected COVID-19. The vast majority of the studies performed RT-qPCR on the saliva samples and compared the results with the gold standard (a nasopharyngeal swab of the same patient). Results Saliva samples analyzed by RT-qPCR, reverse transcription isothermal amplification (RT-LAMP), spectroscopy, and enzyme-linked immunosorbent assay (ELISA) offer high sensitivity to detect SARS-CoV-2 in the early stages of the disease and among asymptomatic patients as compared to nasopharyngeal swab RT-qPCR. In addition, the self-collection of saliva offers the possibility of receiving telemedicine instructions to carry out the test, reducing the risk of contagion. Conclusions The diagnosis of COVID-19 through saliva is sensitive, non-invasive, and is of low risk for the healthcare professionals. However, further studies are recommended to validate its clinical use. Key words: Saliva, SARS-CoV, COVID19, Salivas.

Isothermal amplification and fluorescent detection of SARS-CoV-2 and SARS-CoV-2 variant virus in nasopharyngeal swabs

“…The fluorescent RT-LAMP assays were performed in triplicate using the same NP samples that were previously determined to be positive for SARS-CoV-2 (n = 50) by the UGA Diagnostic Laboratories. The fluorescent RT-LAMP assay values for the SARS-CoV-2 N gene-positive NP samples ranged from 18 to 28 minutes with an overall mean of 23 minutes and 95% CI [22][23][24]. The results for N gene-positive NP samples showed 98% (n = 41/42) concordance with RT-qPCR for SARS-CoV-2 positivity (Table 1).…”

“…The endpoint for LAMP can be real-time detection using fluorescence or absorbance [20]. The RT-LAMP assay has been shown to detect SARS-CoV-2 in �30 minutes using patient samples such as saliva and nasopharyngeal swabs [21,22]. However, to achieve these results, the sample preparation includes a viral RNA extraction step that increases the cost and time required to perform the assay.…”

“…One specimen (n = 1/42) had discordant results in the fluorescent RT-LAMP assay as it failed to produce a signal above the background in the 30 min assay time. The average fluorescent RT-LAMP assay value (23 minutes) is calculated for the group of positive samples (n = 41) at the 95%CI, 23[22][23][24]. Samples having (no Ct) result in RT-qPCR (8/50) had discordant fluorescent RT-LAMP results signified by a positive signal in the RT-LAMP assay (n = 7/8).…”

COVID-19 and Dentistry

“…The specificity of saliva samples is also reported to be not higher than 42% [38]. Additionally, a systematic review of articles reported that saliva can be effectively used for short-and long-term monitoring of humoral immunity against SARS-CoV-2 through primary infection or vaccines [39].…”

COVID-19 Seroprevalence and Active Infection in an Asymptomatic Population

“…NP swabs are invasive, require special personal protective equipment (PPE) and trained expertise for sample collection, and have been prone to supply chain shortages thereby limiting the capacity of testing. Saliva has been shown to be a robust alternative biofluid that provides comparable results to NP swabs and is more easily collected, reducing the need for trained technicians and minimizing PPE requirements (17)(18)(19)(20)(21)(22). Another alternative to the current standard is using a different detection assay, for example reverse transcription loop-mediated isothermal amplification (RT-LAMP) (14,15,(23)(24)(25)(26).…”