PM2.5 Exposure and the Prognosis of Severe Fever with Thrombocytopenia Syndrome: An Integrated Epidemiological and Experimental Study.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with substantial mortality. While fine particulate matter (PM2.5) is a recognized risk factor for multiple infectious diseases, its role in the prognosis of SFTS remains unexplored. In a cohort of 3583 hospitalized SFTS patients, we found that long-term pre-admission exposure to ambient PM2.5 was significantly associated with an increased risk of SFTS-attributable death, with a corresponding hazard ratio of 1.16 (95% CI: 1.04 and 1.30) per 10 μg/m3 increment. Exploratory mediation analysis suggested that viral load partially explains this association. In a model-based counterfactual burden assessment, we estimated that 137 SFTS-attributable deaths in Xinyang during 2010-2022 might have been potentially avoidable under a hypothetical scenario in which annual PM2.5 concentrations complied with the Chinese National Ambient Air Quality Standards. Complementary experimental studies showed that PM2.5 pre-exposure exacerbated SFTSV infection, increasing viral replication and tissue injury. Transcriptomic analyses implicated mitochondrial redox metabolism and reactive-oxygen-species-related pathways, while ROS/MDA measurements and N-acetylcysteine intervention supported PM2.5-induced oxidative priming as a plausible upstream contributing mechanism for enhanced SFTSV replication and disease severity. In summary, this study provides epidemiological evidence linking long-term PM2.5 exposure to poorer SFTS prognosis and suggests a biologically plausible role of oxidative stress-related redox imbalance. These findings highlight the potential relevance of air-quality improvement for reducing severe outcomes of SFTS in endemic regions.