Parallel Analysis of Pharmaceuticals and Viruses in Wastewater: An Untargeted Approach to Tracking Population-Level Respiratory Illness Burden

1Wastewater-based surveillance is widely used for the detection and tracking of priority respiratory pathogens. In this study, pharmaceuticals are tracked in wastewater as an untargeted indicator of symptoms related to acute respiratory infections and influenza-like illnesses, such as coughing, fever, and pain, coincident to respiratory viral loads. From January 2021 to June 2024, wastewater samples from ten wastewater treatment plants across Switzerland serving 23% of the population were analyzed. The analysis encompassed 15 pharmaceuticals and priority respiratory viruses SARS-CoV-2, respiratory syncytial virus, influenza A, and influenza B. Pharmaceutical data were further benchmarked against national clinical surveillance data on a broader range of respiratory pathogens. The pharmaceutical compounds dextrorphan (indicative of dextromethorphan), pheniramine, clarithromycin, acetaminophen, and codeine showed a strong correlation with respiratory viral loads. This enabled the estimation of pathogen-specific and cumulative symptom burdens in the population. Additionally, notable increases in pharmaceutical loads without corresponding increases in viral loads in 2021 and 2024 signaled high community symptom burdens linked to unsurveilled pathogens. The study demonstrates that pharmaceutical surveillance can inform respiratory disease burden and highlights the broader potential of integrated surveillance to assess population-scale symptoms, indicating emerging public health threats beyond those routinely monitored.