Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis | Public Health | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.153.100.128. Please contact the publisher to request reinstatement.
1.
Marty  FM, Chen  K, Verrill  KA.  How to obtain a nasopharyngeal swab specimen.   N Engl J Med. 2020;382(22):e76. doi:10.1056/NEJMvcm2010260 PubMedGoogle Scholar
2.
Jamal  AJ, Mozafarihashjin  M, Coomes  E,  et al; Toronto Invasive Bacterial Diseases Network COVID-19 Investigators.  Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).   Clin Infect Dis. 2020;ciaa848. doi:10.1093/cid/ciaa848 PubMedGoogle Scholar
3.
Pasomsub  E, Watcharananan  SP, Boonyawat  K,  et al.  Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.   Clin Microbiol Infect. 2020;S1198-743X(20)30278-0. Published online May 15, 2020. doi:10.1016/j.cmi.2020.05.001PubMedGoogle Scholar
4.
Ridgway  JP, Pisano  J, Landon  E, Beavis  KG, Robicsek  A.  Clinical sensitivity of severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests for diagnosing coronavirus disease 2019.   Open Forum Infect Dis. 2020;7(8):a315. doi:10.1093/ofid/ofaa315 PubMedGoogle ScholarCrossref
5.
Liberati  A, Altman  DG, Tetzlaff  J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.   BMJ. 2009;339:b2700. doi:10.1136/bmj.b2700 PubMedGoogle ScholarCrossref
6.
Butler-Laporte  G, Lawandi  A, McDonald  E, Lee  T. Saliva PCR for the diagnosis of SARS-CoV-2: a systematic review and meta-analysis. PROSPERO 2020 CRD42020206551. Accessed September 15, 2020. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206551
7.
Kjaergard  LL, Villumsen  J, Gluud  C.  Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.   Ann Intern Med. 2001;135(11):982-989. doi:10.7326/0003-4819-135-11-200112040-00010 PubMedGoogle ScholarCrossref
8.
Dechartres  A, Altman  DG, Trinquart  L, Boutron  I, Ravaud  P.  Association between analytic strategy and estimates of treatment outcomes in meta-analyses.   JAMA. 2014;312(6):623-630. doi:10.1001/jama.2014.8166 PubMedGoogle ScholarCrossref
9.
Whiting  PF, Rutjes  AW, Westwood  ME,  et al; QUADAS-2 Group.  QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.   Ann Intern Med. 2011;155(8):529-536. doi:10.7326/0003-4819-155-8-201110180-00009 PubMedGoogle ScholarCrossref
10.
Ling  DI, Pai  M, Schiller  I, Dendukuri  N.  A Bayesian framework for estimating the incremental value of a diagnostic test in the absence of a gold standard.   BMC Med Res Methodol. 2014;14:67. doi:10.1186/1471-2288-14-67 PubMedGoogle ScholarCrossref
11.
Graham  PL, Moran  JL.  Robust meta-analytic conclusions mandate the provision of prediction intervals in meta-analysis summaries.   J Clin Epidemiol. 2012;65(5):503-510. doi:10.1016/j.jclinepi.2011.09.012 PubMedGoogle ScholarCrossref
12.
Riley  RD, Higgins  JPT, Deeks  JJ.  Interpretation of random effects meta-analyses.   BMJ. 2011;342:d549. doi:10.1136/bmj.d549 PubMedGoogle ScholarCrossref
13.
Plummer  M. rJAGS: Bayesian graphical models using MCMC. Published November 6, 2019. Accessed September 15, 2020. https://cran.r-project.org/web/packages/rjags/index.html
14.
R Development Core Team.  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2019.
15.
Akgun Dogan  O, Kose  B, Agaoglu  NB,  et al.  Does sampling saliva increase detection of SARS-CoV-2 by RT-PCR? comparing saliva with oro-nasopharyngeal swabs.  Preprint. Posted online July 28, 2020.  medRxiv. 2020.2007.2026.20158618. Google Scholar
16.
Becker  D, Sandoval  E, Amin  A,  et al.  Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting.  Preprint. Posted online May 17, 2020.  medRxiv. doi:10.1101/2020.05.11.20092338Google Scholar
17.
Byrne  RL, Kay  GA, Kontogianni  K,  et al.  Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.  Preprint. Posted online July 11, 2020.  medRxiv. doi:10.1101/2020.07.09.20149534Google Scholar
18.
Kojima  N, Turner  F, Slepnev  V,  et al.  Self-collected oral fluid and nasal swab specimens demonstrate comparable sensitivity to clinician-collected nasopharyngeal swab specimens for the detection of SARS-CoV-2.  Published online October 19, 2020.  Clin Infect Dis. doi:10.1093/cid/ciaa1589 PubMedGoogle Scholar
19.
Teo  AKJ, Choudhury  Y, Tan  IB,  et al.  Validation of saliva and self-administered nasal swabs for COVID-19 testing.  Preprint. Posted online August 14, 2020.  medRxiv. doi:10.1101/2020.08.13.20173807 Google Scholar
20.
Vogels  CBF, Brackney  D, Wang  J,  et al.  SalivaDirect: simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance.  Preprint. Posted online September 28, 2020.  medRxiv. doi:10.1101/2020.08.03.20167791Google Scholar
21.
Yokota  I, Shane  PY, Okada  K,  et al.  Mass screening of asymptomatic persons for SARS-CoV-2 using saliva.   Clin Infect Dis. Published online September 25, 2020. doi:10.1093/cid/ciaa1388PubMedGoogle Scholar
22.
Miller  M, Jansen  M, Bisignano  A,  et al.  Validation of a self-administrable, saliva-based RT-qPCR test detecting SARS-CoV-2.  Preprint. Posted online June 9, 2020.  medRxiv. doi:10.1101/2020.06.05.20122721Google Scholar
23.
Caulley  L, Corsten  M, Eapen  L,  et al.  Salivary detection of COVID-19.   Ann Intern Med. Published online August 28, 2020. doi:10.7326/M20-4738PubMedGoogle Scholar
24.
Hanson  KE, Barker  AP, Hillyard  DR,  et al.  Self-collected anterior nasal and saliva specimens versus health care worker-collected nasopharyngeal swabs for the molecular detection of SARS-CoV-2.   J Clin Microbiol. 2020;58(11):e01824-20. doi:10.1128/JCM.01824-20 PubMedGoogle Scholar
25.
McCormick-Baw  C, Morgan  K, Gaffney  D,  et al.  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(8):e01109-20. doi:10.1128/JCM.01109-20 PubMedGoogle Scholar
26.
Cheuk  S, Wong  Y, Tse  H,  et al.  Posterior oropharyngeal saliva for the detection of SARS-CoV-2.   Clin Infect Dis.Published online June 21, 2020. PubMedGoogle Scholar
27.
Iwasaki  S, Fujisawa  S, Nakakubo  S,  et al.  Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva.   J Infect. 2020;81(2):e145-e147. doi:10.1016/j.jinf.2020.05.071 PubMedGoogle ScholarCrossref
28.
Landry  ML, Criscuolo  J, Peaper  DR.  Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients.   J Clin Virol. 2020;130:104567. doi:10.1016/j.jcv.2020.104567PubMedGoogle Scholar
29.
Williams  E, Bond  K, Zhang  B, Putland  M, Williamson  DA.  Saliva as a noninvasive specimen for detection of SARS-CoV-2.   J Clin Microbiol. 2020;58(8):e00776-20. doi:10.1128/JCM.00776-20 PubMedGoogle Scholar
30.
Goldfarb  DM, Tilley  P, Al-Rawahi  GN,  et al.  Self-collected saline gargle samples as an alternative to healthcare worker collected nasopharyngeal swabs for COVID-19 diagnosis in outpatients.  Preprint. Posted online September 14, 2020.  medRxiv. doi:10.1101/2020.09.13.20188334 Google Scholar
31.
Chau  NVV, Thanh Lam  V, Thanh Dung  N,  et al; OUCRU COVID-19 research group.  The natural history and transmission potential of asymptomatic SARS-CoV-2 infection.   Clin Infect Dis. 2020;71(10):2679-2687. doi:10.1093/cid/ciaa711PubMedGoogle ScholarCrossref
32.
Wyllie  AL, Fournier  J, Casanovas-Massana  A,  et al.  Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2.   N Engl J Med. 2020;383(13):1283-1286. doi:10.1056/NEJMc2016359 PubMedGoogle ScholarCrossref
33.
Rao  M, Rashid  FA, Sabri  FSAH,  et al.  Comparing nasopharyngeal swab and early morning saliva for the identification of SARS-CoV-2.   Clin Infect Dis. Published online August 6, 2020. doi:10.1093/cid/ciaa1156PubMedGoogle Scholar
34.
To  KK, Tsang  OT, Yip  CC,  et al.  Consistent detection of 2019 novel coronavirus in saliva.   Clin Infect Dis. 2020;71(15):841-843. doi:10.1093/cid/ciaa149 PubMedGoogle ScholarCrossref
35.
Boulware  DR, Pullen  MF, Bangdiwala  AS,  et al.  A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19.   N Engl J Med. 2020;383(6):517-525. doi:10.1056/NEJMoa2016638 PubMedGoogle ScholarCrossref
36.
Campbell  JR, Uppal  A, Oxlade  O,  et al.  Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs.   CMAJ. 2020;192(40):E1146-E1155. doi:10.1503/cmaj.201128PubMedGoogle ScholarCrossref
37.
Van Lancker  W, Parolin  Z.  COVID-19, school closures, and child poverty: a social crisis in the making.   Lancet Public Health. 2020;5(5):e243-e244. doi:10.1016/S2468-2667(20)30084-0 PubMedGoogle ScholarCrossref
38.
Stage  HB, Shingleton  J, Ghosh  S, Scarabel  F, Pellis  L, Finnie  T.  Shut and re-open: the role of schools in the spread of COVID-19 in Europe.  Preprint. Posted online June 26, 2020.  medRxiv. doi:10.1101/2020.06.24.20139634 Google Scholar
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Characterizing imperfect gold standards.
    Elizabeth Jenny-Avital |
    Coupling PCR tests (nasopharyngeal, saliva) with serial antibody titer might better characterize the performance characteristics of PCR viz false negative and false positive PCR tests....or teach us more about the imperfection of antibody tests.
    CONFLICT OF INTEREST: None Reported
    Original Investigation
    January 15, 2021

    Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Royal Victoria Hospital, Montréal, Québec, Canada
    • 2Department of Critical Care Medicine, National Institutes of Health, Clinical Center, Bethesda, Maryland
    • 3Centre for Outcomes Research, McGill University Health Centre, Montréal, Québec, Canada
    • 4Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Québec, Canada
    • 5Division of General Internal Medicine, Department of Medicine, McGill University, Montréal, Québec, Canada
    JAMA Intern Med. 2021;181(3):353-360. doi:10.1001/jamainternmed.2020.8876
    Key Points

    Question  Is saliva nucleic acid amplification testing (NAAT) comparable to nasopharyngeal NAAT, the current noninvasive criterion standard test for diagnosis of coronavirus disease 2019?

    Findings  In this systematic review and latent class meta-analysis adjusting for the imperfect reference standard, saliva NAAT had a similar sensitivity and specificity to that of nasopharyngeal NAAT.

    Meaning  Given the ease of use and good diagnostic performances, these findings suggest that saliva NAAT represents an attractive alternative to nasopharyngeal swab NAAT and may significantly bolster massive testing efforts.

    Abstract

    Importance  Nasopharyngeal swab nucleic acid amplification testing (NAAT) is the noninvasive criterion standard for diagnosis of coronavirus disease 2019 (COVID-19). However, it requires trained personnel, limiting its availability. Saliva NAAT represents an attractive alternative, but its diagnostic performance is unclear.

    Objective  To assess the diagnostic accuracy of saliva NAAT for COVID-19.

    Data Sources  In this systematic review, a search of the MEDLINE and medRxiv databases was conducted on August 29, 2020, to find studies of diagnostic test accuracy. The final meta-analysis was performed on November 17, 2020.

    Study Selection  Studies needed to provide enough data to measure salivary NAAT sensitivity and specificity compared with imperfect nasopharyngeal swab NAAT as a reference test. An imperfect reference test does not perfectly reflect the truth (ie, it can give false results). Studies were excluded if the sample contained fewer than 20 participants or was neither random nor consecutive. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the risk of bias.

    Data Extraction and Synthesis  Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed for the systematic review, with multiple authors involved at each stage of the review. To account for the imperfect reference test sensitivity, we used a bayesian latent class bivariate model for the meta-analysis.

    Main Outcomes and Measures  The primary outcome was pooled sensitivity and specificity. Two secondary analyses were performed: one restricted to peer-reviewed studies, and a post hoc analysis limited to ambulatory settings.

    Results  The search strategy yielded 385 references, and 16 unique studies were identified for quantitative synthesis. Eight peer-reviewed studies and 8 preprints were included in the meta-analyses (5922 unique patients). There was significant variability in patient selection, study design, and stage of illness at which patients were enrolled. Fifteen studies included ambulatory patients, and 9 exclusively enrolled from an outpatient population with mild or no symptoms. In the primary analysis, the saliva NAAT pooled sensitivity was 83.2% (95% credible interval [CrI], 74.7%-91.4%) and the pooled specificity was 99.2% (95% CrI, 98.2%-99.8%). The nasopharyngeal swab NAAT had a sensitivity of 84.8% (95% CrI, 76.8%-92.4%) and a specificity of 98.9% (95% CrI, 97.4%-99.8%). Results were similar in secondary analyses.

    Conclusions and Relevance  These results suggest that saliva NAAT diagnostic accuracy is similar to that of nasopharyngeal swab NAAT, especially in the ambulatory setting. These findings support larger-scale research on the use of saliva NAAT as an alternative to nasopharyngeal swabs.

    ×