Wastewater-based epidemiology for comprehensive community health diagnostics in a national surveillance study: Mining biochemical markers in wastewater.

This manuscript showcases results from a large scale and comprehensive wastewater-based epidemiology (WBE) study focussed on multi-biomarker suite analysis of both chemical and biological determinants in 10 cities and towns across England equating to a population of ∼7 million people. Multi-biomarker suite analysis, describing city metabolism, can provide a holistic understanding to encompass all of human, and human-derived, activities of a city in a single model: from lifestyle choices (e.g. caffeine intake, nicotine) through to health status (e.g. prevalence of pathogenic organisms, usage of pharmaceuticals as proxy for non-communicable disease, NCD, conditions or infectious disease status), and exposure to harmful chemicals due to environmental and industrial sources (e.g. pesticide intake via contaminated food and industrial exposure). Population normalised daily loads (PNDLs) of many chemical markers were found, to a large extent, driven by the size of population contributing to wastewater (especially NCDs). However, there are several exceptions providing insights into chemical intake that can inform either disease status in various communities or unintentional exposure to hazardous chemicals: e.g. very high PNDLs of ibuprofen in Hull resulting from its direct disposal (confirmed by ibuprofen/2-hydroxyibuprofen ratios) and bisphenol A (BPA) in Hull, Lancaster and Portsmouth likely related to industrial discharge. An importance for tracking endogenous health markers such as 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, an oxidative stress marker) as a generic marker of health status in communities was observed due to increased levels of HNE-MA seen at Barnoldswick wastewater treatment plant that coincided with higher-than-average paracetamol usage and SARS-CoV-2 prevalence in this community. PNDLs of virus markers were found to be highly variable. Being very prevalent in communities nationwide during sampling, SARS-CoV-2 presence in wastewater was to a large extent community driven. The same applies to the fecal marker virus, crAssphage, which is very prevalent in urban communities. In contrast, norovirus and enterovirus showed much higher variability in prevalence across all sites investigated, with clear cases of localized outbreaks in some cities while maintaining low prevalence in other locations. In conclusion, this study clearly demonstrates the potential for WBE to provide an integrated assessment of community health which can help target and validate policy interventions aimed at improving public health and wellbeing.