Is oropharyngeal sampling a reliable test to detect SARS-CoV-2?
Authors: Tobias Todsen, Nikolai Kirkby, Thomas Benfield
Journal: The Lancet Infectious Diseases (2021)

We would like to congratulate Nicole Tsang and colleagues on their clinically relevant systematic review and meta-analysis of the diagnostic performance of different sampling methods to detect SARS-CoV-2 by RT-PCR.1Tsang NNY So HC Ng KY Cowling BJ Leung GM Ip DKM Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.Lancet Infect Dis. 2021; (published online April 12.)https://doi.org/10.1016/S1473-3099(21)00146-8Summary Full Text Full Text PDF PubMed Scopus (177) Google Scholar The authors concluded that, compared with a nasopharyngeal swab, a pooled nasal and oropharyngeal swab offered the best alternative sampling approach to diagnose SARS-CoV-2 infection, followed by saliva and nasal swabs. Oropharyngeal swabs were not recommended for diagnosis because of low sensitivity and positive predictive value. In the meta-analysis, the gold standard was nasopharyngeal swab, such that any other sample that gave a positive SARS-CoV-2 RT-PCR test (eg, saliva, nasal swab, or oropharyngeal swab) was categorised as a false positive if the nasopharyngeal sample was negative for the same individual. We are concerned that this approach might have introduced bias. To illustrate, we used data from a study by Xiong Wang and colleagues,2Wang X Tan L Wang X et al.Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously.Int J Infect Dis. 2020; 94: 107-109Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar which was included in Tsang and colleagues' review. In this study,2Wang X Tan L Wang X et al.Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously.Int J Infect Dis. 2020; 94: 107-109Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar 192 individuals were concomitantly tested using a nasopharyngeal and an oropharyngeal swab, of whom 19 (10%) tested positive by one or both tests. Seven (37%) of 19 patients had tests that were concordant and 12 (63%) were discordant; seven of 12 were positive by nasopharyngeal swab and five were positive by oropharyngeal swab. In their meta-analysis, Tsang and colleagues calculated the sensitivity of the oropharyngeal swab to be 50% (seven of 14) and the specificity to be 93% (178 of 192).1Tsang NNY So HC Ng KY Cowling BJ Leung GM Ip DKM Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.Lancet Infect Dis. 2021; (published online April 12.)https://doi.org/10.1016/S1473-3099(21)00146-8Summary Full Text Full Text PDF PubMed Scopus (177) Google Scholar However, if the reference had been any positive sample from the upper airway, the sensitivity of a nasopharyngeal swab would have been reduced from 100% to 74%, and the sensitivity of an oropharyngeal swab would have increased from 50% to 63%—ie, the difference would have been 11 percentage points and not the 50 percentage points reported by Tsang and colleagues. Nevertheless, a nasopharyngeal swab would remain numerically more sensitive than an oropharyngeal swab.1Tsang NNY So HC Ng KY Cowling BJ Leung GM Ip DKM Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.Lancet Infect Dis. 2021; (published online April 12.)https://doi.org/10.1016/S1473-3099(21)00146-8Summary Full Text Full Text PDF PubMed Scopus (177) Google Scholar Nasopharyngeal swabbing is a challenging procedure and improper sample collection is known to contribute to false-negative results.3Kinloch NN Ritchie G Brumme CJ et al.Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results.J Infect Dis. 2020; 222: 899-902Crossref PubMed Scopus (68) Google Scholar We think that the reference for assessing different sampling methods must be a sample method that tests positive in any upper airway sample, because RT-PCR has a very high specificity to detect SARS-CoV-2. This view is also that of WHO, which recommends combining nasopharyngeal and oropharyngeal swabs to improve diagnostic accuracy.4WHOCOVID-19 clinical management: living guidance. Version WHO/2019-nCoV/clinical/2021.1. World Health Organization, GenevaJan 25, 2021https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1Date accessed: May 15, 2021Google Scholar Further research is warranted to improve the evidence base on, and guide recommendations for, the optimal sampling technique that yields the highest diagnostic accuracy among individuals presenting in ambulatory care.5Todsen T Tolsgaard M Folke F et al.SARS-CoV-2 in saliva, oropharyngeal and nasopharyngeal specimens.Dan Med J. 2021; 68A01210087PubMed Google Scholar We declare no competing interests. Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysisOur 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. Full-Text PDF Is oropharyngeal sampling a reliable test to detect SARS-CoV-2? – Authors' replyWe thank Tobias Todsen and colleagues for their comments on our recent systematic review and meta-analysis comparing the diagnostic performance of different sampling methods to detect SARS-CoV-2 by RT-PCR.1 Based on the findings of one included study,2 they questioned whether any positive sample from the upper airway would be a better gold standard than the traditional nasopharyngeal swab. This method corresponds with a practice that has also been used previously by a small number of studies.3,4 Here, we repeat the random-effects meta-analysis, including all 23 studies and using any positive respiratory sample as the reference gold standard. Full-Text PDF