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      The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs : A Systematic Review and Meta-analysis

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      , MD, , , MD, , PhD
      Annals of Internal Medicine
      American College of Physicians

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          Abstract

          This systematic review summarizes evidence comparing the sensitivities for detection of SARS-CoV-2 infection between nasopharyngeal swabs and saliva samples and estimates the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs.

          Abstract

          Background:

          Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment.

          Purpose:

          To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs.

          Data Sources:

          Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars.

          Study Selection:

          Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection.

          Data Extraction:

          Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2).

          Data Synthesis:

          Thirty-seven studies with 7332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower (95% CI, 9.9 percentage points lower to 3.1 percentage points higher) than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva's sensitivity was 1.5 percentage points higher (CI, 7.3 percentage points lower to 10.3 percentage points higher) than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less (CI, 14.7 percentage points less to 0.8 percentage point more) sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more (95% uncertainty interval, 5 fewer to 166 more) persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8093.

          Limitation:

          The reference standard was imperfect, and saliva collection procedures varied.

          Conclusion:

          Saliva sampling seems to be a similarly sensitive and less costly alternative that could replace nasopharyngeal swabs for collection of clinical samples for SARS-CoV-2 testing.

          Primary Funding Source:

          McGill Interdisciplinary Initiative in Infection and Immunity. (PROSPERO: CRD42020203415)

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          Most cited references42

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          Measuring inconsistency in meta-analyses.

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            QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

            In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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              How to perform a meta-analysis with R: a practical tutorial

              Meta-analysis is of fundamental importance to obtain an unbiased assessment of the available evidence. In general, the use of meta-analysis has been increasing over the last three decades with mental health as a major research topic. It is then essential to well understand its methodology and interpret its results. In this publication, we describe how to perform a meta-analysis with the freely available statistical software environment R, using a working example taken from the field of mental health. R package meta is used to conduct standard meta-analysis. Sensitivity analyses for missing binary outcome data and potential selection bias are conducted with R package metasens. All essential R commands are provided and clearly described to conduct and report analyses. The working example considers a binary outcome: we show how to conduct a fixed effect and random effects meta-analysis and subgroup analysis, produce a forest and funnel plot and to test and adjust for funnel plot asymmetry. All these steps work similar for other outcome types. R represents a powerful and flexible tool to conduct meta-analyses. This publication gives a brief glimpse into the topic and provides directions to more advanced meta-analysis methods available in R.
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                Author and article information

                Journal
                Ann Intern Med
                Ann Intern Med
                aim
                Annals of Internal Medicine
                American College of Physicians
                0003-4819
                1539-3704
                12 January 2021
                : M20-6569
                Affiliations
                [1 ]McGill University and McGill International TB Centre, Montreal, Quebec, Canada, and State University of Rio de Janeiro, Rio de Janeiro, Brazil (M.L.B.)
                [2 ]McGill University, Montreal, Quebec, Canada (S.P.)
                [3 ]McGill University, McGill International TB Centre, and Montreal Chest Institute, Montreal, Quebec, Canada (D.M.)
                [4 ]McGill University and McGill International TB Centre, Montreal, Quebec, Canada (J.R.C.)
                Author notes
                Note: Drs. Campbell and Menzies affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Acknowledgment: The authors thank Genevieve Gee of The Millar Group for providing costs of personal protective equipment in Canada.
                Financial Support: By grant ECRF-01-30 from the McGill Interdisciplinary Initiative in Infection and Immunity (Drs. Menzies and Campbell); this grant supports the salary of Ms. Perlman-Arrow. Dr. Campbell receives salary support from the Fonds de Recherche du Québec—Santé (award #287869), and Dr. Bastos receives salary support from a Canadian Institutes of Health Research grant (FRD331745).
                Reproducible Research Statement: Study protocol: Registered on PROSPERO (CRD42020203415). Statistical code and data set: All data and analytic code used in this study are contained in the article and supplemental content.
                Corresponding Author: Jonathon R. Campbell, PhD, McGill University, Office 3D.13, 5252 Boulevard de Maisonneuve O, Montreal, QC H4A 3S5, Canada; e-mail, jonathon.campbell@ 123456mail.mcgill.ca .
                Current Author Addresses: Dr. Bastos: 5252 Boulevard de Maisonneuve O, Office 3D.54, Montreal, QC H4A 3S5, Canada.
                Ms. Perlman-Arrow: 5252 Boulevard de Maisonneuve O, Office 3D.55, Montreal, QC H4A 3S5, Canada.
                Dr. Menzies: 5252 Boulevard de Maisonneuve O, Office 3D.58, Montreal, QC H4A 3S5, Canada.
                Dr. Campbell: 5252 Boulevard de Maisonneuve O, Office 3D.13, Montreal, QC H4A 3S5, Canada.
                Author Contributions: Conception and design: M.L. Bastos, S. Perlman-Arrow, D. Menzies, J.R. Campbell.
                Analysis and interpretation of the data: M.L. Bastos, S. Perlman-Arrow, D. Menzies, J.R. Campbell.
                Drafting of the article: M.L. Bastos, J.R. Campbell.
                Critical revision of the article for important intellectual content: M.L. Bastos, S. Perlman-Arrow, D. Menzies, J.R. Campbell.
                Final approval of the article: M.L. Bastos, S. Perlman-Arrow, D. Menzies, J.R. Campbell.
                Statistical expertise: M.L. Bastos, J.R. Campbell.
                Obtaining of funding: D. Menzies, J.R. Campbell.
                Administrative, technical, or logistic support: S. Perlman-Arrow, J.R. Campbell.
                Collection and assembly of data: M.L. Bastos, S. Perlman-Arrow, J.R. Campbell.
                Correction: This article was corrected on 22 January 2021 to fix misalignment of 9 row headings in the figure.
                Author information
                https://orcid.org/0000-0003-0582-8870
                https://orcid.org/0000-0002-2257-0624
                https://orcid.org/0000-0003-1601-4514
                https://orcid.org/0000-0003-2341-2166
                Article
                aim-olf-M206569
                10.7326/M20-6569
                7822569
                33428446
                ed8e8c1c-bada-4c8c-a75b-e7bfdeab39c2
                Copyright @ 2021

                This article is made available via the PMC Open Access Subset for unrestricted re-use for research, analyses, and text and data mining through PubMed Central. Acknowledgement of the original source shall include a notice similar to the following: "© 2020 American College of Physicians. Some rights reserved. This work permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited." These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                Categories
                Reviews
                9871, Saliva
                3122457, COVID-19
                2892, Systematic reviews
                9971, Research laboratories
                3006, Prevention, policy, and public health
                5733, Nurses
                2237, Outpatients
                6354, Upper respiratory tract infections
                2357, Health care providers
                9895, Clinical trial reporting
                early, Currently Online First
                coronavirus, Coronavirus Disease 2019 (COVID-19)
                poc-eligible, POC Eligible

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