Relative Sensitivity of Saliva and Upper Airway Swabs for Initial Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Ambulatory Patients
2021; Elsevier BV; Volume: 23; Issue: 3 Linguagem: Inglês
10.1016/j.jmoldx.2020.12.008
ISSN1943-7811
Autores Tópico(s)Dental Research and COVID-19
ResumoSaliva has been proposed as an alternative to upper airway swabs when testing for severe acute respiratory syndrome coronavirus 2. Although some studies have suggested higher viral loads and clinical sensitivity when testing saliva, studies have been relatively small and have given rise to contradictory results. To better understand the relative performance characteristics of saliva and upper airway samples, I performed a rapid systematic review (registered on PROSPERO as CRD42020205035), focusing on studies that included at least 20 subjects who provided diagnostic saliva and upper airway samples on the same day, which were tested by nucleic acid amplification methods and for which a confusion matrix could be constructed for based on a composite reference standard. Nineteen studies comprising 21 cohorts that met predetermined acceptance criteria were identified following a search of PubMed, medRxiv, and bioRxiv. Seven of these cohorts were incorporated into a meta-analysis using a random effects model, which suggests that nasopharyngeal swabs are somewhat more sensitive than saliva samples for the diagnosis of early disease in ambulatory patients, such as in drive-through centers or community health centers. Nevertheless, the difference is modest, and the reduced need for personal protective equipment for saliva sampling may justify the difference. Conclusions are limited by the significant heterogeneity of disease prevalence in the study populations and variation in the approaches to saliva sample collection. Saliva has been proposed as an alternative to upper airway swabs when testing for severe acute respiratory syndrome coronavirus 2. Although some studies have suggested higher viral loads and clinical sensitivity when testing saliva, studies have been relatively small and have given rise to contradictory results. To better understand the relative performance characteristics of saliva and upper airway samples, I performed a rapid systematic review (registered on PROSPERO as CRD42020205035), focusing on studies that included at least 20 subjects who provided diagnostic saliva and upper airway samples on the same day, which were tested by nucleic acid amplification methods and for which a confusion matrix could be constructed for based on a composite reference standard. Nineteen studies comprising 21 cohorts that met predetermined acceptance criteria were identified following a search of PubMed, medRxiv, and bioRxiv. Seven of these cohorts were incorporated into a meta-analysis using a random effects model, which suggests that nasopharyngeal swabs are somewhat more sensitive than saliva samples for the diagnosis of early disease in ambulatory patients, such as in drive-through centers or community health centers. Nevertheless, the difference is modest, and the reduced need for personal protective equipment for saliva sampling may justify the difference. Conclusions are limited by the significant heterogeneity of disease prevalence in the study populations and variation in the approaches to saliva sample collection. Rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection is important for treatment of symptomatic individuals, for disrupting transmission by asymptomatic carriers, and for understanding the dynamics of infection in communities.1Tu Y.-P. O'Leary T.J. Testing for severe acute respiratory syndrome–coronavirus 2: challenges in getting good specimens, choosing the right test, and interpreting the results.Crit Care Med. 2020; 48: 1680-1689Crossref PubMed Scopus (13) Google Scholar Although the use of flocked swabs to obtain nasopharyngeal (NP) specimens for testing has constituted the gold standard for upper respiratory system (URS) sampling, uses of specimens obtained by swabbing the oropharynx, midturbinate, and anterior nares (AN; alias nasal) have all served as alternatives, both as a result of supply shortages and because these sites can be self-sampled, reducing clinician exposure and the need for personal protective equipment. Saliva, which can also be obtained without clinician assistance, has been proposed as a safe, easy, and comfortable way to obtain samples for coronavirus disease 2019 (COVID-19) testing,2Wyllie A.L. Fournier J. Casanovas-Massana A. Campbell M. Tokuyama M. Vijayakumar P. et al.Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2.N Engl J Med. 2020; 383: 1283-1286Crossref PubMed Scopus (634) Google Scholar but published studies have been based on heterogeneous study populations and have given conflicting results.3Rose D. Ranoa E. Holland R.L. Alnaji F.G. Green K.J. Wang L. Brooke C.B. Burke M.D. Fan T.M. Hergenrother P.J. Saliva-based molecular testing for SARS-CoV-2 that bypasses RNA extraction.BioRxiv. 2020; ([Epub] doi:10.1011/2020.06.18.159434)PubMed Google Scholar, 4Landry M.L. Criscuolo J. Peaper D.R. Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients.J Clin Virol. 2020; 130: 104567Crossref PubMed Scopus (109) Google Scholar, 5Pasomsub E. Watcharananan S.P. Boonyawat K. Janchompoo P. Wongtabtim G. Suksuwan W. Sungkanuparph S. Phuphuakrat A. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.Clin Microbiol Infect. 2020; ([Epub ahead of print] doi:10.1016/j.cmi.2020.05.001)Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar, 6Griesemer S. Van Slyke G. Ehrbar D. Strle K. Yildirim T. Centurioni D. Walsh A. Chang A. Waxman M. St George K. Evaluation of specimen types and saliva stabilization solutions for SARS-CoV-2 testing.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.16.20133041)Google Scholar, 7Hanson K.E. Barker A.P. Hillyard D.R. Gilmore N. Barrett J.W. Orlandi R.R. Shakir S.M. Self-collected anterior nasal and saliva specimens versus healthcare worker-collected nasopharyngeal swabs for the molecular detection of SARS-CoV-2.J Clin Microbiol. 2020; 58 (e01824-20)Crossref PubMed Scopus (115) Google Scholar, 8Becker D. Sandoval E. Amin A. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. De Hoff P. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting.medRxiv. 2020; ([Epub] doi:10.1101/2020.05.11.20092338)Google Scholar In this article, we set out to answer the question. "When nucleic acid amplification tests for SARS-CoV-2 are employed for initial diagnosis, what is the relative sensitivity for detection of virus when saliva samples are used rather than nasopharyngeal, oropharyngeal, midturbinate, or anterior nares swabs?" To answer this question, I conducted a rapid systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles,9McGrath T.A. Alabousi M. Skidmore B. Korevaar D.A. Bossuyt P.M.M. Moher D. Thombs B. McInnes M.D.F. Recommendations for reporting of systematic reviews and meta-analyses of diagnostic test accuracy: a systematic review.Syst Rev. 2017; 6: 194Crossref PubMed Scopus (105) Google Scholar using analysis that relies on a composite reference standard (CRS)10Baughman A.L. Bisgard K.M. Cortese M.M. Thompson W.W. Sanden G.N. Strebel P.M. Utility of composite reference standards and latent class analysis in evaluating the clinical accuracy of diagnostic tests for pertussis.Clin Vaccin Immunol. 2008; 15: 106-114Crossref PubMed Scopus (66) Google Scholar based on both swabs and saliva samples; this approach is not biased against either sample type. The study is registered on PROSPERO (https://www.crd.york.ac.uk/prospero; CRD42020205035), but a complete protocol has not been published. PubMed, medRxiv, and bioRxiv were searched over the interval from January 1, 2020, to August 17, 2020. Preliminary searches showed that a combination of the terms COVID-19 and saliva was able to capture all or nearly all relevant articles in which synonymous terms, such as SARS-CoV-2, novel coronavirus, or oral fluid, appeared. For this reason, a simple search string for saliva COVID-19 sensitivity was used with all three databases to identify articles for further screening. Several additional articles were identified after initial peer review. Following the initial identification of articles, the titles and abstracts were screened to eliminate articles not meeting the prespecified inclusion criteria. Articles remaining after this process were rescreened, particularly because many of the articles reviewed were in the form of research letters that did not have an abstract. Ultimately, 19 articles that met inclusion criteria were available for analysis, as shown in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram11Moher D. Liberati A. Tetzlaff J. Altman D.G. The PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6: 194Crossref Scopus (49820) Google Scholar (Supplemental Figure S1). To be included in this systematic review, studies were required to include a minimum of 20 individual subjects; each subject must have had both a saliva specimen and at least one of several URS swab specimens [nasopharyngeal swabs (NPSs), oropharyngeal swabs, midturbinate swabs, or AN (or nasal) swabs] obtained on the same day. Articles that reported on tongue and cheek swabbing, without a specific effort to soak up saliva, were not included. Each of these specimens must have undergone analysis for SARS-CoV-2 sequences using either an isothermal amplification or an RT-PCR–based method. Results must have been reported in a manner that allowed construction of a confusion matrix, based on a single sample-pair per patient, including the saliva- and upper airway–based test. If an article reported patients who were tested multiple times, and a confusion matrix could not be constructed that reflected results of the first NPS/saliva pair, that study was excluded. Studies in which discrepant analysis was used to resolve diagnostic conflicts between the two sites were not to be included unless data could be analyzed independently of the discrepant analysis. In the event that multiple time points were included in one of the included studies, only the first time point was to be used in my analysis. If confusion matrices could only be constructed from data involving multiple time points from the same patients, the study was excluded. No attempt was made to obtain data from the investigators involved in these published studies. When articles that were identified on bioRxiv or medRxiv were compared with those on PubMed, an additional six duplicate articles were eliminated. Four articles that were not identified by the search strategy were added.1Tu Y.-P. O'Leary T.J. Testing for severe acute respiratory syndrome–coronavirus 2: challenges in getting good specimens, choosing the right test, and interpreting the results.Crit Care Med. 2020; 48: 1680-1689Crossref PubMed Scopus (13) Google Scholar The potential for bias associated with each study was evaluated using the QUADAS212Whiting P.F. Rutjes A.W.S. Westwood M.E. Mallett S. Deeks J.J. Reitsma J.B. Leeflang M.M.G. Sterne J.A.C. Bossuyt P.M.M. Quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies.Ann Intern Med. 2011; 155: 529-536Crossref PubMed Scopus (9066) Google Scholar,13Schueler S. Schuetz G.M. Dewey M. The revised QUADAS-2 tool.Ann Intern Med. 2012; 156 (author reply 323-324): 323Crossref PubMed Scopus (63) Google Scholar instrument. The risk of spectrum bias was assessed from the perspective of testing as an initial diagnostic method for ambulatory patients; the bias assessment does not constitute a judgement on the quality of the study, which may have been performed to demonstrate assay validity, assessment of recovery, or other purposes different than that for which I evaluated potential bias. Seven articles with a low risk of bias that were deemed appropriate to include in a meta-analysis were analyzed using a diagnostic effects model (der Simion–Laird),14DerSimonian R. Laird N. Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188Abstract Full Text PDF PubMed Scopus (31444) Google Scholar as implemented by OpenMetaAnalyst15Wallace B.C. Dahabreh I.J. Trikalinos T.A. Lau J. Trow P. Schmid C.H. Closing the gap between methodologists and end-users: R as a computational back-end.J Stat Softw. 2012; 49: 1-15Crossref Scopus (843) Google Scholar software program. A predetermined data extraction form included study author, type of study, inclusion and exclusion criteria, setting, sample types, swab types, transport medium, manufacturer or description of nucleic acid amplification assays, as well as space to record study results in the form of confusion matrices. After initial compilation and tabulation of data, a second review was undertaken to determine whether saliva samples involved coughing or in other ways included sputum in the sample; this step was not part of the original protocol. Because the choice of any particular sample type as a gold standard provides a biased estimate of relative sensitivity, which compared with all other sample types, a CRS10Baughman A.L. Bisgard K.M. Cortese M.M. Thompson W.W. Sanden G.N. Strebel P.M. Utility of composite reference standards and latent class analysis in evaluating the clinical accuracy of diagnostic tests for pertussis.Clin Vaccin Immunol. 2008; 15: 106-114Crossref PubMed Scopus (66) Google Scholar was computed for each study on the basis of all sample types included in the study, when possible. For one study in which results were not presented in a manner that made this possible, a CRS was computed individually for comparisons of each upper airway sample with the saliva sample. Equivocal results and assay failures were not used in the calculation of sensitivity or in the construction of the CRS for each study. Confidence limits for sensitivity were computed using the Newcombe efficient score method,16Newcombe R.G. Two-sided confidence intervals for the single proportion: comparison of seven methods.Stat Med. 1998; 17: 857-872Crossref PubMed Scopus (3293) Google Scholar as implemented in the Vassarstats Clinical Calculator 1 (http://vassarstats.net, last accessed January 12, 2021) (Table 1).3Rose D. Ranoa E. Holland R.L. Alnaji F.G. Green K.J. Wang L. Brooke C.B. Burke M.D. Fan T.M. Hergenrother P.J. Saliva-based molecular testing for SARS-CoV-2 that bypasses RNA extraction.BioRxiv. 2020; ([Epub] doi:10.1011/2020.06.18.159434)PubMed Google Scholar, 4Landry M.L. Criscuolo J. Peaper D.R. Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients.J Clin Virol. 2020; 130: 104567Crossref PubMed Scopus (109) Google Scholar, 5Pasomsub E. Watcharananan S.P. Boonyawat K. Janchompoo P. Wongtabtim G. Suksuwan W. Sungkanuparph S. Phuphuakrat A. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.Clin Microbiol Infect. 2020; ([Epub ahead of print] doi:10.1016/j.cmi.2020.05.001)Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar, 6Griesemer S. Van Slyke G. Ehrbar D. Strle K. Yildirim T. Centurioni D. Walsh A. Chang A. Waxman M. St George K. Evaluation of specimen types and saliva stabilization solutions for SARS-CoV-2 testing.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.16.20133041)Google Scholar, 7Hanson K.E. Barker A.P. Hillyard D.R. Gilmore N. Barrett J.W. Orlandi R.R. Shakir S.M. Self-collected anterior nasal and saliva specimens versus healthcare worker-collected nasopharyngeal swabs for the molecular detection of SARS-CoV-2.J Clin Microbiol. 2020; 58 (e01824-20)Crossref PubMed Scopus (115) Google Scholar, 8Becker D. Sandoval E. Amin A. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. De Hoff P. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting.medRxiv. 2020; ([Epub] doi:10.1101/2020.05.11.20092338)Google Scholar,17L'Helgouach N. Champigneux P. Santos-Schneider F. Molina L. Espeut J. Alali M. Baptiste J. Cardeur L. Dubuc B. Foulongne V. Galtier F. Makinson A. Marin G. Picot M.-C. Prieux-Lejeune A. Quenot M. Checa-Robles F.J. Salvetat N. Vetter D. Reynes J. Molina F. EasyCOV: LAMP based rapid detection of SARS-CoV-2 in saliva.medRxiv. 2020; ([Epub] doi:10.1101/2020.05.30.20117291)Google Scholar, 18Miller M. Jansen M. Bisignano A. Mahoney S. Wechsbergrg C. Albanese N. Castillo L. Farinas P. Lazarin G.A. Jaremko M. Validation of a self-administrable, saliva-based RT-qPCR test detecting SARS-CoV-2.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.05.20122721)Google Scholar, 19Güçlü E. Koroglu M. Yürümez Y. Toptan H. Kose E. Güneysu F. Karabay O. Comparison of saliva and oro-nasopharyngeal swab sample in the molecular diagnosis of COVID-19.Rev Assoc Med Bras. 2020; 66: 1116-1121Crossref PubMed Scopus (20) Google Scholar, 20Wong S.C.Y. Tse H. Siu H.K. Kwong T.S. Chu M.Y. Yau F.Y.S. Cheung I.Y.Y. Tse C.W.S. Poon K.C. Cheung K.C. Wu T.C. Chan J.W.M. Cheuk W. Lung D.C. Posterior oropharyngeal saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Clin Infect Dis. 2020; 71: 2939-2946Crossref PubMed Scopus (55) Google Scholar, 21Iwasaki S. Fujisawa S. Nakakubo S. Kamada K. Yamashita Y. Fukumoto T. Sato K. Oguri S. Taki K. Senjo H. Sugita J. Hayasaka K. Konno S. Nishida M. Teshima T. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva.J Infect. 2020; 81: e145-e147Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 22Byrne R.L. Kay G.A. Kontogianni K. Brown L. Collins A.M. Cuevas L.E. Ferreira D. Fraser A.J. Garrod G. Hill H. Menzies S. Mitsi E. Owen S.I. Williams C.T. Hyder-Wright A. Adams E.R. Cubas-Atienzar A.I. Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.Emerg Infect Dis. 2020; 26: 2769-2770Crossref Scopus (41) Google Scholar, 23Jamal A.J. Mozafarihashjin M. Coomes E. Powis J. Li A.X. Paterson A. et al.Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Clin Infect Dis. 2020; ([Epub ahead of print] doi:10.1093/cid/ciaa848)Crossref Scopus (134) Google Scholar, 24McCormick-Baw C. Morgan K. Gaffney D. Cazares Y. Jaworski K. Byrd A. Molberg K. Cavuoti D. Saliva as an alternate specimen source for detection of SARS-CoV-2 in symptomatic patients using Cepheid Xpert Xpress SARS-CoV-2.J Clin Microbiol. 2020; 58 (e01109-20)Crossref PubMed Scopus (93) Google Scholar, 25Yokota I. Shane P.Y. Okada K. Unoki Y. Yang Y. Inao T. Sakamaki K. Iwasaki S. Hayasaka K. Sugita J. Nishida M. Fujisawa S. Teshima T. Mass screening of asymptomatic persons for SARS-CoV-2 using saliva.Clin Infect Dis. 2020; ([Epub ahead of print] doi:10.1093/cid/ciaa1388)Crossref PubMed Scopus (102) Google Scholar, 26Kojima N. Turner F. Slepnev V. Bacelar A. Deming L. Kodeboyina S. Klausner J.D. Self-collected oral fluid and nasal swab specimens demonstrate comparable sensitivity to clinician-collected nasopharyngeal swab specimens for the detection of SARS-CoV-2.Clin Infect Dis. 2020; ([Epub ahead of print] doi:10.1093/cid/ciaa1589)Crossref Scopus (87) Google Scholar, 27SoRelle J.A. Mahimainathan L. McCormick-Baw C. Cavuoti D. Lee F. Thomas A. Sarode R. Clark A.E. Muthukumar A. Saliva for use with a point of care assay for the rapid diagnosis of COVID-19.Clin Chim Acta. 2020; 510: 685-686Crossref PubMed Scopus (18) Google Scholar, 28Dogan O.A. Kose B. Agaoglu N.B. Yildiz J. Alkurt G. Kendir Demirkol Y. Irvem A. Dinler-Doganay G. Doganay L. Does sampling saliva increase detection of SARS-CoV-2 by RT-PCR? comparing saliva with oro-nasopharyngeal swabs.J Virol Methods. 2021; 290: 114049Crossref PubMed Scopus (22) Google Scholar, 29Rao M. Rashid F.A. Sabri F.S.A.H. Jamil N.N. Zain R. Hashim R. Amran F. Kok H.T. Samad M.A.A. Ahmad N. Comparing nasopharyngeal swab and early morning saliva for the identification of SARS-CoV-2.Clin Infect Dis. 2020; ([Epub ahead of print] doi:/10.1093/cid/ciaa1156)Crossref Scopus (91) Google Scholar Criteria for performing a formal meta-analysis were as follows: i) studies used the same amplification technology (such as RT-PCR); ii) studies used the same upper airway sample site (AN, midturbinate, and NP could be included together, but not admixed with studies based on oropharynx samples); iii) studies enrolled a similar patient mix (eg, symptomatic, asymptomatic, or hospitalized) and similar clinical environment (drive-through/community health center or hospital).Table 1Study Characteristics and Sampling Method SensitivityAuthorsPatient characteristicsSettingPotential for spectrum bias∗Potential for spectrum bias was evaluated in terms of the enrolled cohort. Although a group of 200 consecutively enrolled hospital patients would not be considered as experiencing selection bias, it would be viewed as having a high potential for spectrum bias (with regards to this study) because all patients were sufficiently ill as to require hospitalization. Similarly, a group of patients selected on the basis of RT-PCR Ct values would be considered biased (no matter what those values were).nPositive, %Sensitivity, % (95% CI)SalivaNP swabOP swabNasal self-swabRose3Rose D. Ranoa E. Holland R.L. Alnaji F.G. Green K.J. Wang L. Brooke C.B. Burke M.D. Fan T.M. Hergenrother P.J. Saliva-based molecular testing for SARS-CoV-2 that bypasses RNA extraction.BioRxiv. 2020; ([Epub] doi:10.1011/2020.06.18.159434)PubMed Google ScholarNot statedDrive-through testing centerLow100989 (51–99)100 (63–100)Jamal17L'Helgouach N. Champigneux P. Santos-Schneider F. Molina L. Espeut J. Alali M. Baptiste J. Cardeur L. Dubuc B. Foulongne V. Galtier F. Makinson A. Marin G. Picot M.-C. Prieux-Lejeune A. Quenot M. Checa-Robles F.J. Salvetat N. Vetter D. Reynes J. Molina F. EasyCOV: LAMP based rapid detection of SARS-CoV-2 in saliva.medRxiv. 2020; ([Epub] doi:10.1101/2020.05.30.20117291)Google ScholarSymptomatic inpatients with COVID-19HospitalHigh189488 (66–98)94 (69–100)Landry4Landry M.L. Criscuolo J. Peaper D.R. Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients.J Clin Virol. 2020; 130: 104567Crossref PubMed Scopus (109) Google ScholarSymptomatic outpatientsDrive-through testing centerLow1242886 (69–95)94 (79–99)Pasomsub5Pasomsub E. Watcharananan S.P. Boonyawat K. Janchompoo P. Wongtabtim G. Suksuwan W. Sungkanuparph S. Phuphuakrat A. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.Clin Microbiol Infect. 2020; ([Epub ahead of print] doi:10.1016/j.cmi.2020.05.001)Abstract Full Text Full Text PDF PubMed Scopus (216) Google ScholarSymptomatic, asymptomatictravelers and contactsHospital respiratory infection clinicLow2001186 (62–96)90 (68–98)Dogan18Miller M. Jansen M. Bisignano A. Mahoney S. Wechsbergrg C. Albanese N. Castillo L. Farinas P. Lazarin G.A. Jaremko M. Validation of a self-administrable, saliva-based RT-qPCR test detecting SARS-CoV-2.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.05.20122721)Google ScholarHospitalized, possible COVID-19, moderateto severe diseaseHospitalHigh1613758 (45–71)92 (81–97)93 (83–98)Yokota19Güçlü E. Koroglu M. Yürümez Y. Toptan H. Kose E. Güneysu F. Karabay O. Comparison of saliva and oro-nasopharyngeal swab sample in the molecular diagnosis of COVID-19.Rev Assoc Med Bras. 2020; 66: 1116-1121Crossref PubMed Scopus (20) Google ScholarAsymptomaticAirportLow17630.280 (30–99)100 (46–100)Yokota19Güçlü E. Koroglu M. Yürümez Y. Toptan H. Kose E. Güneysu F. Karabay O. Comparison of saliva and oro-nasopharyngeal swab sample in the molecular diagnosis of COVID-19.Rev Assoc Med Bras. 2020; 66: 1116-1121Crossref PubMed Scopus (20) Google ScholarAsymptomaticContact tracingLow1612994 (81–98)87 (74–95)Byrne20Wong S.C.Y. Tse H. Siu H.K. Kwong T.S. Chu M.Y. Yau F.Y.S. Cheung I.Y.Y. Tse C.W.S. Poon K.C. Cheung K.C. Wu T.C. Chan J.W.M. Cheuk W. Lung D.C. Posterior oropharyngeal saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Clin Infect Dis. 2020; 71: 2939-2946Crossref PubMed Scopus (55) Google ScholarSymptomatic patientsHospitalHigh1101386 (56–97)Griesemer6Griesemer S. Van Slyke G. Ehrbar D. Strle K. Yildirim T. Centurioni D. Walsh A. Chang A. Waxman M. St George K. Evaluation of specimen types and saliva stabilization solutions for SARS-CoV-2 testing.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.16.20133041)Google ScholarSymptomatic patients and asymptomatic contacts in a known hotspotDrive-through testing centerLow2274187 (78–93)98 (92–100)92 (84–97)Griesemer6Griesemer S. Van Slyke G. Ehrbar D. Strle K. Yildirim T. Centurioni D. Walsh A. Chang A. Waxman M. St George K. Evaluation of specimen types and saliva stabilization solutions for SARS-CoV-2 testing.medRxiv. 2020; ([Epub] doi:10.1101/2020.06.16.20133041)Google ScholarSymptomatic and asymptomaticMedical center testing tentLow2365.250 (22–78)100 (70–100)42 (16–71)Miller21Iwasaki S. Fujisawa S. Nakakubo S. Kamada K. Yamashita Y. Fukumoto T. Sato K. Oguri S. Taki K. Senjo H. Sugita J. Hayasaka K. Konno S. Nishida M. Teshima T. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva.J Infect. 2020; 81: e145-e147Abstract Full Text Full Text PDF PubMed Scopus (171) Google ScholarSymptomatic or asymptomatic with previous positive PCRPhysician officesHigh914097 (84–100)94 (80–99)Hanson7Hanson K.E. Barker A.P. Hillyard D.R. Gilmore N. Barrett J.W. Orlandi R.R. Shakir S.M. Self-collected anterior nasal and saliva specimens versus healthcare worker-collected nasopharyngeal swabs for the molecular detection of SARS-CoV-2.J Clin Microbiol. 2020; 58 (e01824-20)Crossref PubMed Scopus (115) Google Scholar†Data are not presented in a way that allows generation of a composite reference that includes all three specimen types. Sensitivity values of saliva samples and nasal samples are each computed from separate composite references that include saliva/NP and nasal/NP, respectively.SymptomaticDrive-through testing centerLow3542494 (86–98)93 (85–97)86 (77–93)L'Helgouach22Byrne R.L. Kay G.A. Kontogianni K. Brown L. Collins A.M. Cuevas L.E. Ferreira D. Fraser A.J. Garrod G. Hill H. Menzies S. Mitsi E. Owen S.I. Williams C.T. Hyder-Wright A. Adams E.R. Cubas-Atienzar A.I. Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.Emerg Infect Dis. 2020; 26: 2769-2770Crossref Scopus (41) Google ScholarAsymptomatichealth care workersHospitalHigh924.3100 (40–100)0 (0–60)Iwasaki23Jamal A.J. Mozafarihashjin M. Coomes E. Powis J. Li A.X. Paterson A. et al.Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Clin Infect Dis. 2020; ([Epub ahead of print] doi:10.1093/cid/ciaa848)Crossref Scopus (134) Google ScholarSymptomatic, some previously diagnosedwith COVID-19HospitalHigh761390 (54–99)90 (54–99)Becker8Becker D. Sandoval E. Amin A. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. De Hoff P. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Hoff P.D.E. Diets A. Leonetti N. Lim Y.W. Elliott C. Laurent L. Grzymski J. Lu J.T. Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting.medRxiv. 2020; ([Epub] doi:10.1101/2020.05.11.20092338)Google ScholarProbably symptomatic‡Although the article did not explicitly identify these patients as symptomatic, at the time the work was done symptomatic patients were the focus of most community testing.Community testing environmentLow772060 (33–83)100 (93–100)SoRelle24McCormick-Baw C. Morgan K. Gaffney D. Cazares Y. Jaworski K. Byrd A. Molberg K. Cavuoti D. Saliva as an alternate specimen source for detection of SARS-CoV-2 in symptomatic patients using Cepheid Xpert Xpress SARS-CoV-2.J Clin Microbiol. 2020; 58 (e01109-20)Crossref PubMed Scopus (93) Google Scholar§NP samples were tested using RT-PCR, whereas the saliva samples were tested using ID NOW. 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