An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients

HALFON, P.; PENARANDA, G.; KHIRI, H.; GARCIA, V.; DROUET, H.; PHILIBERT, P.; PSOMAS, C.; DELORD, M.; ALLEMAND-SOURRIEU, J.; RETORNAZ, F.; CHARPIN, C.; Gonzales, T.; PEGLIASCO, H.; ALLARDET-SERVENT, J.

Background: Diagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19. Methods: From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RTqPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates. Results: The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%;81%), 99% (95% CI95%;100%), 99% (95%CI 93%;100%), and 78% (95%CI 70%;85%), 0.28 (95%CI 0.21;0.39), and 72 (95%CI 10;208) respectively. Sensitivity was higher for patients with Ct [≤] 25 regardless of TSO: TSO [≤] 4 days 92% (95%CI 75%;99%), TSO > 4 days 100% (95%CI 54%;100%), and asymptomatic 100% (95%CI 78%;100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed. Conclusions: This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.