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Estimating the prevalence of infectious disease in a community is useful for public health resource allocation, policy making, and messaging. When diseases such as COVID-19 become endemic in the community it is essential to have passive indicators that do not depend on voluntary testing data. Our team is working with public health departments to use wastewater to inform our understanding of COVID-19 prevalence in communities throughout Illinois. We have developed a generalized methodology to improve the predictive power of wastewater from treatment plants in the Chicago area. Connecting measured SARS-CoV-2 RNA to community prevalence is challenging, due to variations in the contributing population, the variable rate of wastewater flow, and the complexity of wastewater media, which impacts RNA decay rates and lab measurement accuracy. To quantify the impact of these factors we also track …