AbstractThe COVID-19 has severely affected economies and health systems around the world. Mass testing could work as a powerful alternative to restrain disease dissemination, but the shortage of reagents is a limiting factor. A solution to optimize test usage relies on ‘grouping’ or ‘pooling’ strategies, which combine a set of individuals in a single reaction. To compare different group testing configurations, we developed the poolingr package, which performs an innovative hybrid in silico/in vitro approach to search for optimal testing configurations. We used 6759 viral load values, observed in 2389 positive individuals, to simulate a wide range of scenarios. We found that larger groups (>100) framed into multi-stage setups (up to six stages) could largely boost the power to detect spreaders. Although the boost was dependent on the disease prevalence, our method could point to cheaper grouping schemes to better mitigate COVID-19 dissemination through identification and quarantine recommendation for positive individuals.