Antipyretic Surveillance in Wastewater: A Tool for Assessing Public Health and Tracking Ongoing “Disease X”

Wastewater-based epidemiology (WBE) based on viral surveillance has proven effective in combating COVID-19. More recently, symptom-based drug monitoring has gained traction with the expansion of wastewater monitoring systems worldwide. However, its integration into predictive models to support public health management and its comparative value relative to viral surveillance remain underexplored. Here, we monitored ibuprofen and acetaminophen in wastewater in Beijing, China, during the COVID-19 surge and postpandemic phases. By combining antipyretic concentrations with known human excretion rates, we estimated the number of individuals with fever and incorporated this into the SEIR model (I_p-I_s-I_a) that includes asymptomatic infections. Notably, there is a systematic lead of the antipyretic-based incidence compared to the SARS-CoV-2-derived incidence, indicating that the antipyretic signal leads throughout the surge period. In the postpandemic scenario with alternating prevalence of COVID-19 and influenza, the antipyretic levels reflected the population-wide infection dynamics for both diseases. As fever is an important physiological response to infection, discrepancies between antipyretic usage and molecular biosurveillance data may serve as early signals of emerging fever-inducing “Disease X”. This study highlights the potential of integrating antipyretic biomarkers into WBE to improve the early detection of outbreaks and support public health preparedness.