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

  1. Vânia M. Moreira
  2. Paulo Mascarenhas
  3. Vanessa Machado
  4. João Botelho
  5. José João Mendes
  6. Nuno Taveira
  7. M. Gabriela Almeida

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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).

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  1. Version published to 10.3390/diagnostics11020363
  2. ScreenIT

    SciScore for 10.1101/2021.01.19.21250094: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy and study selection: Search strategies were carried out in different databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) until December 4th, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    We used Mendeley reference manager to organize records and remove duplicates.
    Mendeley
    suggested: (Mendeley Data, RRID:SCR_002750)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    An additional limitation is that some of these works failed to properly describe the percentage of patients having asymptomatic, pre-symptomatic or symptomatic statuses, as the VL varies significantly in these patients and may negatively affect the accuracy of saliva as an index specimen. To further improve the saliva collecting protocol and secure its clinical validation and utility, specifically designed studies shall be performed, overcoming current methodological limitations. Concerning the other evaluated index specimens, sputum presented an elevated risk of delivering false positive results when compared to NPS/OPS RT-PCR. Nevertheless, we must be cautious in interpreting these results due to the small number of studies. Similarly, tears/CS delivered the lowest sensitivity and yet, the highest specificity though, once again, these results were based on scarce data. As for the CT analyses, due to the low number of available studies, these estimates are inconclusive at this stage. From the sampling standpoint, both saliva and sputum can be easily collected; however, 72% of COVID-19 patients may not produce enough sputum for analysis 53. Therefore, saliva (oral region) seems to be the best specimen for both public health and epidemiologic measures 52. Because saliva can be self-collected by patients at home or the outbreak spot, it would decrease the exposure of health-care workers to infections, and reduce the waiting times for sample collection 52. On the contrary, DTS/P...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.01.19.21250094v1 on medRxiv