Diagnosis of SARS-Cov-2 Infection by RT-PCR Using Specimens Other Than Naso- and Oropharyngeal Swabs: A Systematic Review and Meta-Analysis

Abstract

The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling techniques, yet, these have some limitations such as the complexity of collection. Hence, several other types of specimens that are easier to obtain are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab (CS) against standard specimens (NPS, OPS, or a combination of both). In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December, 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). We identified 1560 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0–98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4–88.8) and specificity of 96.4% (95% CI: 89.5–98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3–95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3–96.9) and specificity of 63.1% (95% CI: 36.8–89.3). The remaining index specimens could not be adequately assessed given the lack of studies available. Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity; therefore, these appear to be the best candidates for alternative specimens to NPS/OPS in SARS-CoV-2 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial, since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or at outbreak control spots (e.g., schools, airports, and nursing homes).

Diagnostic accuracy and acceptability of molecular diagnosis of COVID-19 on saliva samples relative to nasopharyngeal swabs in tropical hospital and extra-hospital contexts: The COVISAL study

“…These results seem consistent with meta-analyses which observed a difference of sensitivity of RT-PCR generally in favor of nasopharyngeal samples [ 7 , 23 , 24 ]. However, these systematic reviews showed the great heterogeneity of results between studies with many potential differences that were not accounted for.…”

Are Posterior Oropharyngeal Saliva Specimens an Acceptable Alternative to Nasopharyngeal Sampling for the Monitoring of SARS-CoV-2 in Primary-Care Settings?

“…To obtain an enhanced saliva sample [ 19 , 20 ], patients with ARI were instructed and supervised by physicians to produce saliva coughed up from the posterior oropharynx (by clearing the throat or gargle) as this kind of sample seems to be much more sensitive than saliva from the oral cavity alone or from salivary glands [ 21 ]. However, recent studies suggested that oral cavity saliva specimens and deep throat sputum offer high sensitivity and specificity too [ 22 , 23 ].…”

“…Finally, we collected saliva coughed up from the posterior oropharynx (by clearing the throat or gargle). However, recent studies suggested that oral cavity saliva specimens and deep throat sputum also offer high sensitivity and specificity [ 22 , 23 ].…”

Testing Saliva to Reveal the Submerged Cases of the COVID-19 Iceberg

“…Compared to the gold standard nasopharyngeal swab, testing saliva for SARS-CoV-2 has been shown to have at least equal, and sometimes higher, sensitivity for detecting asymptomatic carriers (Savela et al, 2021;Yokota et al, 2021). Recent meta-analyses comparing the efficiency of PCR detection when applied to nasopharyngeal and saliva samples (Butler-Laporte et al, 2021;Cañete et al, 2021;Khiabani and Amirzade-Iranaq, 2021;Lee et al, 2021;Moreira et al, 2021), confirm the high specificity of saliva, with sensitivity positively correlating with stage of infection (i.e., early) and sampling technique (Tan et al, 2021).…”