Diagnostic performance of antigen testing for severe acute respiratory syndrome coronavirus 2

To the Editor:

We read the brief report by Villaverde et al¹ in which the authors posit a low diagnostic performance of antigen testing for severe acute respiratory syndrome coronavirus 2 in children. We agree that reverse transcriptase polymerase chain reaction (RT-PCR) testing is the diagnostic gold standard and that it would be desirable to perform timely RT-PCR testing in every suspect case, which unfortunately is not realistic. After a detailed consideration of their article, we want to offer the following remarks.

When validating a diagnostic tool a proper definition of the gold standard is required.² The authors claimed that testing targeted E and RdRp genes,¹ but no description of the RT-PCR kit or kits that were used were presented, nor were the definitions of “positive RT-PCR test” specified in terms of the required number of replicated genes and the cycle threshold cut-off values. Because in a pandemic setting even a low viral load in a symptomatic patient should prompt a coronavirus disease 2019 (COVID-19) diagnosis,³ the quantitative aspect of this issue seems to be minor in contrast to the reproducibility issues.

In addition, the study is stated to be retrospective,¹ so it is unclear why (and how many) patients were asked consent for paired sampling, and when the sample size was estimated. If patients truly were enrolled retrospectively, selection criteria and whether paired sampling was standard of care in the participating centers should be clarified. Simply put, a diagnostic test validation study should not have a retrospective design.²

Lastly, we want to remark that 98 out of every 100 negative-testing patients in the study were not infected by severe acute respiratory syndrome coronavirus 2,¹ which should be reassuring for clinicians in their everyday emergency department practice.