Diagnosis of SARS-Cov-2 infection using specimens other than naso- and oropharyngeal swabs: a systematic review and meta-analysis
Authors: Moreira Vânia M. , Mascarenhas Paulo , Machado Vanessa , Botelho João , Mendes José João , Taveira Nuno , Almeida M. Gabriela 
Published: January 2021

SUMMARYBackgroundThe 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, yet, with some limitations. Several specimens that are easier to collect 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).MethodsIn 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. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2).FindingsWe identified 3022 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). Remaining index specimens presented uncertainty given the lack of studies available.InterpretationOur meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 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 outbreak control spots (e.g. schools, airports, and nursing homes).FundingNothing to declare.Research in contextEvidence before this studyThe lack of systematized data on the accuracy performance of alternative specimens for the detection of SARS-CoV-2 (against the standard NPS/OPS). The ever-growing number of studies available, made this updated systematic review timely and of the utmost importanceAdded value of this studyOur meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 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.Implications of all the available evidenceSaliva samples simply taken from the oral cavity are promising alternatives to the currently used nasal/throat swabs. Saliva specimens can be self-collected, mitigate the discomfort caused by sampling, reduce the transmission risk and increase testing capacity. Therefore, the validation of this alternative specimen will promote the implementation of truly deployable rapid tests for SARS-CoV-2 detection at the point-of-care or outbreak spots.