This study describes wastewater concentrations of SARS-CoV-2 at seven different sampling locations in Southern Nevada (ranging from 4.2 to 8.7 log10 gc/L) and highlights several key variables affecting those concentrations, including COVID-19 incidence, sample type, and service area population. This information is important for implementing wastewater-based epidemiology, but it also provides insight relevant to the design and regulation of potable reuse systems. Specifically, smaller systems may be more prone to influent concentration spikes that can drive enteric pathogen risk during disease outbreaks. It may be possible to leverage reactor hydraulics to achieve peak “averaging” in these scenarios, although it then becomes important to consider how elevated risks at the lower percentiles potentially offset benefits at the upper percentiles. Informed by SARS-CoV-2 concentration dynamics, the current study simulated relative risk for a hypothetical enteric pathogen. Simulated reactor hydraulics (i.e., dispersion) increased pathogen concentrations by up to 2.6 logs at lower percentiles but also decreased concentrations by up to 1.1 logs at the upper percentiles that sometimes drive public health risk. Collectively, these data highlight the importance of considering outbreak conditions, pathogen spikes, and peak “averaging” in the design and operation of treatment systems and in the development of regulatory frameworks.