THE AUTHOR REPLIES

I thank Dr. Saha-Chaudhuri (1) for her observations. Saha-Chaudhuri raises some important cautions about pooled testing. Pooled testing is most advantageous when applied to a population with a low prevalence rate. It should not be used for symptomatic people and is of limited value for those in high-risk settings like nursing homes.

As Saha-Chaudhuri points out (1), a typical assay has a limit of detection, and one must account for effects of dilution when specimens are to be pooled. However, analytical studies have found little reduction in sensitivity for reverse transcription polymerase chain reaction (RT-PCR) even with up to a 32-fold mix of a positive specimen with negative specimens (2). Based on confirmatory pilot work, 10-fold pooling is currently being used at the National Institutes of Health to perform a weekly screen of asymptomatic on-campus staff, so that positive persons can be quarantined and offered care and their contacts can be traced. Pooling is now also being used in the state of Nebraska, in Germany, and in Rwanda. The gold-standard RT-PCR test for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has specificity approaching 100%. While there are evidently false-negative results, especially prior to the development of symptoms (3), the problem may not primarily be with the assay itself. For both practical and biological reasons, sometimes little or no virus is captured in a nasopharyngeal swab, but there is reason to suspect that during those times infectivity would also be low.

A major remaining issue with testing has to do with the unfortunate fact that the swabbing procedure itself is unpleasant, and people will want to avoid it. We hope that a nasal swab or a saliva-based test can be effective enough to replace nasopharyngeal swabbing.

Saha-Chaudhuri points out the dangers of “clearing” people to return to work (1), but the same caution applies for individual testing. No one is really “clear,” as you could be negative today and positive tomorrow; but regular screens of asymptomatic people will find the infected people early and provide an important tool for controlling the spread of this disease. We mustn’t let the perfect be the enemy of the good, and we need to be able to help return people to their connected and productive lives.

ACKNOWLEDGMENTS

Conflict of interest: none declared.

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