Tsang NNY, So HC, Ng KY, et al. Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis. Lancet Infect Dis. 2021 Apr 12. pii: S1473-3099(21)00146-8. doi: 10.1016/S1473-3099(21)00146-8.

BACKGROUND: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods.

METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation.

FINDINGS: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 =30%) was observed in studies on saliva and nasal swabs.

INTERPRETATION: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens.

FUNDING: Hong Kong Research Grants Council.

Ratings by Clinicians (at least 3 per Specialty)
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Hospital Doctor/Hospitalists
Internal Medicine
Family Medicine (FM)/General Practice (GP)
Emergency Medicine
General Internal Medicine-Primary Care(US)
Public Health
Infectious Disease
Comments from MORE raters

Emergency Medicine rater

This meta-analysis evaluated the performance of sampling methods of SARS-CoV-2 RT-PCR. The authors included 23 studies (7973 patients and 16762 samples). Pooled nasal and throat swabs demonstrated highest sensitivity (97%), followed by nasal swabs (86%), and saliva (85%). Throat swabs had the lowest sensitivity at 68%. Specificities were high for all collection methods. Self-collection and healthcare-collected specimens demonstrated similar test characteristics. Throat swabs should not be used for diagnosis, but the other swabs evaluated are promising. In particular, nasal and saliva swabs are not as uncomfortable as nasopharyngeal swabs, which are considered the current gold standard. There are several limitations including significant heterogeneity in saliva and nasal swabs and disease prevalence. The study setting and type of swab were also skewed. Finally, the meta-analysis focused on patients with COVID symptoms or history of exposure presenting in an ambulatory setting.

Family Medicine (FM)/General Practice (GP) rater

Very important information that deserves wide dissemination because it could increase the availability of testing.

General Internal Medicine-Primary Care(US) rater

This metanalysis of studies in 7973 patients showed that compared with the gold standard of nasopharyngeal swabs, pooled saliva and nasal swabs were the best, nasal swabs and pharyngeal swabs were satisfactory, but throat swabs did not perform as well.

General Internal Medicine-Primary Care(US) rater

Interesting. As more testing is required for travel, etc, this becomes important. Example, to travel to Jamaica to certain resorts you need a negative PCR nasal from a CLIA-certified lab within 72 hours of departing by air. The resort does the same within 3 days of returning stateside. Not sure what others are doing. The self-testing that is done in this community: They take it home and then drop it back, which is why it does not qualify for travel outside of the USA. Whose throat was swabbed?

General Internal Medicine-Primary Care(US) rater

They evaluated test performance only in outpatients/ambulatory patients, not hospitalized patients. So, PPV and NPV cannot be extrapolated to inpatients where prevalence of disease may be different. Otherwise, very useful, timely, and clinically relevant.

Hospital Doctor/Hospitalists rater

This is a relevant study as it highlights newer and less invasive alternatives to effectively detect the presence of SARS-CoV-2, which can facilitate its detection in the community.

Infectious Disease rater

Useful but not surprising information.