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

Abstract

Background: Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies.

Methods: We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data.

Results: We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting.

Conclusions: These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

Keywords: Epidemiology; Infectious diseases; Population screening.

Fig. 1. Diagnostic sensitivity of RT-PCR and rapid antigen tests.

Specifying an incubation period of 4.4 days (to symptom onset; vertical dashed line), the estimated diagnostic sensitivity of an RT-PCR test based on data from Hellewell et al. (black stars) and rapid antigen test LumiraDx (light-blue squares); Sofia (green diamonds); BinaxNOW (yellow triangles); BD Veritor (dark-red circles); and CareStart (purple hexagram) based on percent positive agreement data from Emergency Use Authorization documentation over the course of infection.

Fig. 2. Probability of post-quarantine transmission.

Specifying a negative-binomial distribution for expected post-quarantine transmission, 35.1% of infections being asymptomatic, a 24-h delay in obtaining RT-PCR test results, no delay in receiving rapid antigen test results, an incubation period of 4.4 days, self-isolation upon symptom onset, and the diagnostic sensitivity curve for RT-PCR based on data from Hellewell et al, the probability of post-quarantine transmission when conducting an RT-PCR test only on exit (solid line; black stars) and the rapid antigen tests (dashed lines) LumiraDx (light-blue squares); Sofia (green diamonds); BinaxNOW (yellow triangles); BD Veritor (dark-red circles); and CareStart (purple hexagram) performed a on exit and b on both entry and exit; and the fraction of the 18 rapid antigen tests whose use conferred a lower probability of post-quarantine transmission than did an RT-PCR test conducted 24 h before exit from quarantine, when the rapid antigen test was conducted c on exit and d on both entry and exit. The whiskers denote the 95% credible interval based on 1,000 samples of an RT-PCR diagnostic sensitivity curve and rapid antigen percent positive agreement curve conducted through importance sampling.

Fig. 3. Effective reproduction number in the context of different frequencies of serial testing.

Specifying 35.1% of infections as asymptomatic, a 24-h delay in obtaining RT-PCR test results, no delay in receiving rapid antigen test results, an incubation period of 4.4 days, self-isolation upon symptom onset, and a RT-PCR diagnostic sensitivity curve informed by data from Hellewell et al., a the expected effective reproduction number with serial testing using an RT-PCR test (black) and the rapid antigen tests LumiraDx (light-blue); Sofia (green); BinaxNOW (yellow); BD Veritor (dark-red); and CareStart (purple); and b for serial testing every day to every 14 days with a zero- to five-day delay (black to light gray) in obtaining the results for an RT-PCR test and isolation of positives in comparison to no testing (solid gray line). c The mean reduction of the effective reproduction number (with no self-isolation upon symptom onset) of the 18 RA tests (green circles), of RT-PCR with a one-day delay (black stars), and no test (gray line), with self-isolation upon symptom onset. d The fraction of rapid antigen tests of the 18 tests that had an effective reproduction number (R_E) below one for testing frequencies ranging from every day to every 14 days and isolating positives. The whiskers denote the 95% credible interval based on 1,000 samples of an RT-PCR diagnostic sensitivity curve and rapid antigen percent positive agreement curve.

Fig. 4. The effective reproduction number, and risk of one or more false positives, for varying frequencies of serial testing with RT-PCR and rapid antigen tests.

Specifying 35.1% of infections being asymptomatic, a 24-h delay before receiving RT-PCR results, no delay before receiving rapid antigen test results, an incubation period of 4.4 days, self-isolation upon symptom onset, and a RT-PCR diagnostic sensitivity curve informed by data from Hellewell et al., the expected transmission with serial testing using RT-PCR test with no delay to five-day delay (black stars gradient) in obtaining test results and the rapid antigen test LumiraDx (light-blue squares); Sofia (green diamonds); BinaxNOW (yellow triangles); BD Veritor (dark-red circles); and CareStart (purple hexagrams) for testing everyday to every 14 days and isolating positives (small dots: longer time between tests; larger dots: shorter time between tests) and the corresponding probability of at least one false positive over a two-week period (x axis).