Antigen-based rapid diagnostic testing or alternatives for diagnosis of symptomatic COVID-19: A simulation-based net benefit analysis

Background SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) can diagnose COVID-19 rapidly and at low cost, but their lower sensitivity than nucleic acid amplification testing (NAAT) has limited clinical adoption. Methods We compared Ag-RDT, NAAT, and clinical judgment alone for diagnosing symptomatic COVID-19. We considered an outpatient setting (10% COVID-19 prevalence among the patients tested, 3-day NAAT turnaround) and a hospital setting (40% prevalence, 24-hour NAAT turnaround). We simulated transmission from cases and contacts and relationships between time, viral burden, transmission, and case detection. We compared diagnostic approaches using a measure of net benefit that incorporated both clinical and public health benefits and harms of intervention. Results In the outpatient setting, we estimated that using Ag-RDT instead of NAAT to test 200 individuals could have a net benefit equivalent to preventing all symptomatic transmission from one person with COVID-19 (one “transmission-equivalent”). In the hospital setting, net benefit analysis favored NAAT, and testing 25 patients with NAAT instead of Ag-RDT achieved one “transmission-equivalent” of incremental benefit. In both settings, Ag-RDT was preferred to NAAT if NAAT turnaround time exceeded two days. Both Ag-RDT and NAAT provided greater net benefit than management based on clinical judgment alone, unless intervention carried minimal harm and was provided equally regardless of diagnostic approach. Conclusions For diagnosis of symptomatic COVID-19, the speed of diagnosis with Ag-RDT is likely to outweigh its lower accuracy compared to NAAT wherever NAAT turnaround times are two days or longer. This advantage may be even greater if Ag-RDTs are also less expensive.