Identification of early prediction biomarkers of severity in patients with severe fever with thrombocytopenia syndrome based on plasma proteomics.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease. Given its rapid disease progression and high mortality rate, early warning is crucial in improving the outcomes, However, to date, relevant comprehensive predictors or an effective prediction model are still poorly explored. Methods: A plasma proteomic profile was performed at early stages in patients with SFTS. Functional clustering analysis was used to select the candidate proteins and then validate their expression by ELISA. A cohort consisting of 190 patients with SFTS was used to develop the predictive model for severe illness and subsequently validate it in a new cohort consisting of 93 patients with SFTS. Results: A significant increase in plasma proteins associated with various functional clusters, such as the proteasomal protein catabolic process, phagocytosis, and humoral immune response, was observed in severe SFTS patients. High levels of four proteins including NID1, HSP90α, PSMA1, and VCAM1 were strongly correlated with multi-organ damage and disease progression. A prediction model was developed at the early stage to accurately predict severe conditions with the area under the curve of 0.931 (95% CI, 0.885, 0.963). Conclusion: The proteomic signatures identified in this study provide insights into the potential pathogenesis of SFTS. The predictive models have substantial clinical implications for the early identification of SFTS patients who may progress to severe conditions.