Background: Test-trace-isolate programs are an essential part of COVID-19 control that offer a more targeted approach than many other non-pharmaceutical interventions. Effective use of such programs requires methods to estimate their current and anticipated impact. Methods and Findings: We present a mathematical modeling framework to evaluate the expected reductions in the reproductive number, R, from test-trace-isolate programs. This framework is implemented in a publicly available R package and an online application. We evaluated the effects of case detection, speed of isolation, contact tracing completeness and speed of quarantine using parameters consistent with COVID-19 transmission (R0 = 2.5, generation time 6.5 days). We show that R is most sensitive to changes to the proportion of infections detected in almost all scenarios, and other metrics have a reduced impact when case detection levels are low (< 30%). Although test-trace-isolate programs can contribute substantially to reducing R, exceptional performance across all metrics is needed to bring R below one through test-trace-isolate alone, highlighting the need for comprehensive control strategies. Formally framing the dynamical process also indicates that metrics used to evaluate performance of test-trace-isolate, such as the proportion of identified infections among traced contacts, may be misleading. While estimates of program performance are sensitive to assumptions about COVID-19 natural history, our qualitative findings are robust across numerous sensitivity analyses.Conclusions: Effective test-trace-isolate programs first need to be strong in the ”test” com-ponent, as case detection underlies all other program activities. Even moderately effective test-trace-isolate programs are an important tool for controlling the COVID-19 pandemic, and can alleviate the need for more restrictive social distancing measures.
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