LAUSR

To the Editor We read with interest the editorial regarding the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic tests as a screening tool in populations with low prevalence. We agree that use of antibody tests for the novel coronavirus have the potential to be useful for clinical and population health applications. This is particularly true when the prevalence of antibodies in the tested population is at least 10% or greater. As the authors show, lower prevalence results in suboptimal positive predictive values even for serologic tests that have 99% specificity. Of concern to us is how the authors chose to represent the clinical sensitivity of the 10 serologic tests that had been granted emergency use authorization (not approval) by the Food and Drug Administration (FDA) as of April 30, 2020. The sensitivities shown in Table 1 of their article are acknowledged as being derived from information on the FDA website. However, rather than reporting sensitivity (positive percent agreement) relative to the day of coronavirus disease 2019 (COVID-19) symptom onset or diagnosis, the authors chose to calculate sensitivity using the total of all specimens tested, without regard to the timing of sample collection (personal communication from authors). In our opinion, reporting sensitivity in this way is misleading, as it understates the optimal sensitivity, defined as the ability of a test to detect SARS-CoV-2 antibodies when they are present. No test is able to detect antibodies that are not present because they have not yet been produced or are at a concentration that is well below analytical sensitivity, as will happen in very early infection. The authors justified their calculation of sensitivity by stating that the tested population may not always be several days to weeks away from diagnosis. While this is true, the same could be said for any serologic test that is used as a screening test. As an example, the sensitivities of HIV antibody tests are calculated from individuals known to contain antibodies or from seroconversion panels. It is well known that tests for infectious disease antibodies will have lower sensitivities if used in very recently infected patients. The same is true for the novel coronavirus. Calculating and reporting antibody test sensitivity without regard to onset of infection is a practice to be avoided.