We 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. We calculated the sensitivity and negative predictive value (NPV) for each sampling approach (table ).
Table.
Sensitivity and NPV of sampling approaches using nasopharyngeal swab or any positive specimen as the reference comparator
|
Nasopharyngeal swab as reference comparator |
Any positive specimen as reference comparator |
|||
|---|---|---|---|---|
| Sensitivity | NPV | Sensitivity | NPV | |
| Pooled nasal and throat swab | 0·97 (0·93–1·00) | 0·99 (0·98–1·00) | 0·97 (0·93–1·00) | 0·99 (0·98–1·00) |
| Nasopharyngeal swab | 1·00 (ref) | 1·00 (ref) | 0·94 (0·91–0·97) | 0·99 (0·98–1·00) |
| Saliva | 0·85 (0·75–0·93) | 0·97 (0·94–0·98) | 0·87 (0·78–0·93) | 0·97 (0·94–0·98) |
| Nasal swab | 0·86 (0·77–0·93) | 0·95 (0·88–0·99) | 0·87 (0·80–0·93) | 0·95 (0·88–0·99) |
| Throat swab | 0·68 (0·35–0·94) | 0·96 (0·94–0·98) | 0·75 (0·52–0·92) | 0·96 (0·94–0·98) |
Data in parentheses are 95% CIs. NPV=negative predictive value.
The updated results are consistent with our previous conclusion, with pooled nasal and throat swabs offering the best diagnostic performance with sensitivity maintained at 97%, followed by nasopharyngeal swab (sensitivity changed from 100% to 94%), saliva (85% to 87%), and nasal swabs (86% to 87%). Throat swab (68% to 75%) still ranked as the least sensitive approach, with a 22% lower sensitivity than pooled nasal and throat swab (table). Similar to our previous analysis,1 NPVs were comparable and high (range 95–99%) for all sampling approaches.
Although the sensitivity estimate might numerically vary, our results show that the ranking of diagnostic performance remained consistent with the use of a different reference standard. However, using any positive sample as the gold standard makes it impossible to assess the issue of false positivity, which carries non-trivial health-related, financial, and psychological implications,5 and so effectively negates the possibility of doing a proper assessment of test performance through the calculation of specificity and positive predictive value. Together, these reasons might also explain why nasopharyngeal swabbing is being so widely used as the gold standard for diagnosis of SARS-CoV-2 in clinical practice, most studies, and other systematic reviews we examined in our Article.1
In summary, our updated analysis using the alternative gold standard of any positive sample reaffirmed our recommendation of pooled nasal and throat swabs as the best sampling approach that gives the highest sensitivity for diagnosing SARS-CoV-2 infection in the ambulatory care setting, followed by nasopharyngeal swabs, saliva, and nasal swabs. Throat swabs gave a much lower sensitivity and should not be recommended.
We declare no competing interests.
References
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