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Wastewater-Based Epidemiology (WBE) has become a powerful tool for assessing disease occurrence in communities. This study investigates the coronavirus disease 2019 (COVID-19) epidemic in the United States during 2023–2024 using wastewater data from 189 wastewater treatment plants in 40 states and the District of Columbia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pepper-mild mottle virus normalized SARS-CoV-2 RNA concentration data were compared with COVID-19 hospitalization admission data at both national and state levels. We further investigate temporal features in wastewater viral RNA abundance, with peak timing and cross-correlation lag analyses indicating that wastewater SARS-CoV-2 RNA concentrations precede hospitalization admissions by 2 to 12 days. Lastly, we demonstrate that wastewater treatment plant size has a significant effect on the variability of measured SARS-CoV-2 RNA concentrations. This study highlights the effectiveness of WBE as a non-invasive, timely and resource-efficient disease monitoring strategy, especially in the context of declining COVID-19 clinical reporting. [ABSTRACT FROM AUTHOR]