BackgroundPollinosis, commonly known as seasonal allergic rhinoconjuctivitis or hay fever, is the world’s most prevalent allergic disorder, posing substantial health and economic impacts. This study explores the application of wastewater-based epidemiology (WBE) to assess the population-scale burden of pollinosis by correlating antihistamine markers in wastewater with airborne pollen data.MethodsOver two years, 251 wastewater samples – each representing a 24-hour period with excreta from approximately 471,000 individuals – were collected in Zurich (Switzerland). Eleven antihistamine markers were analyzed in the samples using liquid chromatography high-resolution mass spectrometry (LC-HRMS). The relationship between wastewater antihistamine loads – primarily fexofenadine selected due to its high concentrations and stability – and airborne pollen concentrations of 47 taxa was investigated using a linear non-negative least squares regression model.ResultsThe wastewater loads of second-generation antihistamines, namely bilastine, cetirizine, and fexofenadine, displayed a strong seasonal correlation with airborne pollen patterns. For fexofenadine about half of its annual usage was linked to episodes of acute pollen exposure. A noted delay and persistence in consumption implied enduring symptoms following exposure. Grass pollen accounted for a quarter of annual consumption, indicating high population allergy burden. Increases in fexofenadine loads during periods without known allergenic pollen suggested additional triggers for allergy symptoms, potentially yew pollen.ConclusionsThe striking correlation between second-generation antihistamines in wastewater and pollen suggests that WBE is a viable tool to assess population-scale allergy burden. Deciphering the interplay between pollen allergen exposure, prevalence, and symptom severity, requires further research, which would benefit from advancements in automated pollen measurements and the institutionalization of WBE.