Differential Short-term and Long-term Metabolic and Cytokine Responses to Infection of Severe Fever with Thrombocytopenia Syndrome Virus

Abstract Introduction Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS bunyavirus (SFTSV), which has a wide geographic distribution. The primary clinical manifestations of SFTS are fever and thrombocytopenia, with multiorgan failure being the leading cause of death. While most patients recover with treatment, little is known about the potential long-term metabolic effects of SFTSV infection. Objectives The aim of this study was to light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals. Methods In this study, we used untargeted metabolomics to obtain the relative abundance of plasma metabolites from 14 SFTS patients, 18 IgG positive healthy controls and 20 IgG negative healthy controls, respectively, using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). Additionally, the concentrations of 12 cytokines were quantified through mean fluorescence intensity (MFI) measurements. Results and Conclusion We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparison and alalyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, we propose that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients, potentially providing a new perspective for the treatment of SFTS patients.