Comparative analyses of FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation

Abstract

Rapid antigen (RA) tests are being increasingly employed for detection of COVID-19 infections in implementations of quarantine and surveillance. We conducted a comparative analysis of quarantine durations, testing frequencies, and false-positive rates for all of the 18 RA tests for which emergency use authorization (EUA) has been given by the FDA and a nasopharyngeal RT-PCR test. For each test, we employed a mathematical model of imminent infections to calculate the effective reproductive number in the context of the test used for quarantine or serial testing strategy. We informed the model with data on test specificity and temporal diagnostic sensitivity, convolved with a data-driven profile of COVID-19 infectiousness across the disease time course. Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the duration of quarantine and the turnaround time of testing results. When quarantines are shorter than five days, our results suggest that an RA test on entry to and on exit from quarantine would reduce onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to require a minimum frequency of every six days. RA tests reduce RE below one when conducted at a minimum frequency that ranges from every six days to every eight days—depending on the type of RA test—with a median of seven days. Our analysis also highlights that the risk of onward transmission during serial testing increases with the delay in obtaining the results. False-positives were found to be more frequent with RA tests, an issue that could be mitigated with clinical and RT-PCR follow-up. Accounting for the specific diagnostic traits of RA tests, they are an important component of the tool set for policy decision-making, and can serve as a viable alternative to RT-PCR in efforts to control the spread of disease.

Testing for COVID-19 is Much More Effective When Performed Immediately Prior to Social Mixing

“…Independent academic investigations into the relative sensitivity for each rapid antigen test across the disease time course in a practical real-world implementation would enable increasingly accurate quantification of transmission. In a comparison of these real-world tests to those in a controlled clinical setting, a previous study demonstrated that there was similar effectiveness under these different conditions [ 23 ]. Therefore, we expect the effectiveness of each rapid antigen test presented here to be consistent in real-world implementation.…”

“…Our computations use a RT-PCR diagnostic sensitivity curve that was constructed by piecewise mapping using the Cartesian pairing of the relative infectivity—obtained by dividing the infectivity profile by the magnitude of the peak infectivity—to diagnostic sensitivity from the pre- and post-peak infectivity ( Supplementary Figure S1 ). Specifying an incubation period and corresponding distribution from Ashcroft et al [ 22 ], the baseline RT-PCR diagnostic sensitivity curve was obtained from a log-Normal distribution functional form [ 23 ] fit to the serial testing data of 27 healthcare workers from Hellewell et al [ 24 ] using a maximum likelihood approach [ 23 , 24 ]—restricting the time of peak diagnostic sensitivity to the time of peak infectivity ( Supplementary Figure S1 ). The functional form of this RT-PCR diagnostic sensitivity curve and distribution of the incubation period differs from that used in Hellewell et al [ 24 ].…”

“…From our RT-PCR diagnostic sensitivity curve, we constructed diagnostic sensitivity curves for each rapid antigen test using their temporal percent positivity agreement with RT-PCR-indicating that the diagnostic sensitivity of the rapid antigen can be no higher than that of RT-PCR. Specifically, the diagnostic sensitivity of the rapid antigen test at time t is determined by multiplying the diagnostic sensitivity of the RT-PCR test at time t by the percent positive agreement at time t. For each rapid antigen test, a linear logit model was fitted to the percent positive agreement data with a RT-PCR test from the time of symptom onset using a maximum likelihood approach [23]. To determine the percent positive agreement of the rapid antigen test during the incubation period, we used an interpolation function of the infectivity based on the Cartesian pairing of the infectivity and the percent positive agreement.…”

“…The authors acknowledge a degree of textual manuscript overlap with Wells et al [ 23 ] and Wells et al [ 55 ] arising from commonality of methodology regarding the collection and analysis of the percent positive agreement data for all the rapid antigen tests with RT-PCR.…”