Revisiting the Potential Role of Urine in Wastewater Surveillance for COVID-19 and Beyond

The overperformance of wastewater testing during near-source surveillance, especially in venues where defecation is presumed to be de minimis, such as aircraft and nonresidential schools, suggests the possibility of a non-fecal source. To revisit the possibility of urine as an input, data were compiled from 45 studies on SARS-CoV-2 RNA in the urine of 1924 COVID-19 patients. In general, the reporting quality was extremely low. The estimated pooled prevalence of urinary SARS-CoV-2 RNA shedding is 11.3% (95% CI: 8.4–14.3), which roughly agrees with previous reviews. However, the 2-fold prediction interval and wide range of observed prevalences warrant careful consideration of the variability between studies. Among the eight studies reporting sufficient methodological details to estimate the volume of urine being assayed in a single PCR reaction (i.e., the equivalent sample volume, ESV), the RNA urinary shedding prevalence was normally distributed (r² = 1.00) as a function of the ESV. The explanatory power of the ESV suggests the rarity of SARS-CoV-2 RNA in urine could be a methodological artifact. The findings demonstrate that clinical studies designed for clinically relevant hypotheses could produce data subject to important biases relevant to assessing the feasibility of wastewater surveillance.