BackgroundTesting plays a critical role in treatment and prevention responses to the COVID-19 pandemic. Compared to nucleic acid tests (NATs), antigen-detection rapid diagnostic tests (Ag-RDTs) can be more accessible, but typically have lower sensitivity and specificity. By quantifying these trade-offs, we aimed to inform decisions about when an Ag-RDT would offer greater public health value than reliance on NAT.MethodsFollowing an expert consultation, we selected two use cases for analysis: rapid identification of people with COVID-19 amongst patients admitted with respiratory symptoms in a ‘hospital’ setting and early identification and isolation of people with mildly symptomatic COVID-19 in a ‘community’ setting. Using decision analysis, we evaluated the health system cost and health impact (deaths averted and infectious days isolated) of an Ag-RDT-led strategy, compared to a strategy based on NAT and clinical judgement. We adopted a broad range of values for ‘contextual’ parameters relevant to a range of settings, including the availability of NAT and the performance of clinical judgement. We performed a multivariate sensitivity analysis to all of these parameters.ResultsIn a hospital setting, an Ag-RDT-led strategy would avert more deaths than a NAT-based strategy, and at lower cost per death averted, when the sensitivity of clinical judgement is less than 90%, and when NAT results are available in time to inform clinical decision-making for less than 85% of patients. The use of an Ag-RDT is robustly supported in community settings, where it would avert more transmission at lower cost than relying on NAT alone, under a wide range of assumptions.ConclusionsDespite their imperfect sensitivity and specificity, Ag-RDTs have the potential to be simultaneously more impactful, and have a lower cost per death and infectious person-days averted, than current approaches to COVID-19 diagnostic testing.