Wastewater-based proteomics: A proof-of-concept for advancing early warning system for infectious diseases and immune response monitoring

Problem: What if wastewater could reveal diseases spreading in our communities? Traditional disease surveillance methods have limitations in cost, logistics, and ability to reach everyone. Wastewater-based epidemiology (WBE) has emerged as a promising alternative, providing a population-level view by analysing sewage. However, current WBE methods focus on detecting viral RNA, which alone doesn’t give complete picture of disease spread and community immune responses. 

Method: We introduced a novel approach using proteomics—a way to study proteins. This allows us to detect both disease-specific biomarkers, protein signals that indicate a disease and immune response signatures—protein signs showing our bodies are fighting back, providing a comprehensive view of disease spread and the community’s immune reaction.  

Application: We harnessed the power of mass spectrometry (MS) to detect proteins, specifically both SARS-CoV-2, the COVID-19 virus, as our test case and C-reactive protein (CRP), an indicator of inflammation. Our team developed new MS-based bioanalytical pipelines to measure cause-response associations between a pathogen stressor and immune response. We carefully selected three MS-technologies as they provide different capabilities: UHPLC-QqQ, UHPLC-QTOF, and MALDI-TOF/TOF – to detect low abundance peptides in our samples. UHPLC-QqQ proved to be the best performer, offering the highest selectivity and sensitivity for the target analytes. By analysing wastewater samples collected during periods of varying COVID-19 prevalence, we demonstrated the potential of proteomics for real-time disease surveillance. Our proof-of-concept study lays the foundation for more sophisticated WBE systems. By simultaneously tracking both viral presence and immune responses, we can gain valuable insights into the dynamics of disease outbreaks. 

Paper (s): Wastewater-based proteomics: A proof-of-concept for advancing early warning system for infectious diseases and immune response monitoring – ScienceDirect 

A new paradigm in public health assessment: water fingerprinting for protein markers of public health using mass spectrometry 

Partners: Wessex Water 

Funders: EPSRC EWS-C19 project (EP/V028499/1), Wessex Water Services Ltd and EPSRC Impact Acceleration Account (Project number: EP/R51164X/1, ENTRUST IAA) and UKWIR IPC project (Innovative Pathways Control).