A global lipid map of severe fever with thrombocytopenia syndrome virus infection reveals glycerophospholipids as novel prognosis biomarkers.

Unlabelled: Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease caused by a novel bunyavirus characterized by high fever, thrombocytopenia, and multiple organ damage. While lipids play an important role in viral infections, the specific alterations in lipid metabolism during SFTSV infection remain unclear. This study aimed to elucidate the global lipid metabolic profiles of SFTS patients with mild, severe, and fatal outcomes. A total of 60 SFTS patients, consisting of 30 mild, 15 severe and 15 fatal patients, and 30 healthy controls, were enrolled for the investigation of global lipidomics in serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our findings revealed global alterations in the lipid signature induced by SFTSV infection and further confirmed that the glycerophospholipid metabolism pathway was profoundly affected during the progression of mild, severe, and fatal outcomes in SFTS patients. Importantly, LysoPC (20:0) and LysoPC (P-16:0) are strongly correlated with the clinical parameters of SFTSV infection. Furthermore, we demonstrated the substantial prognostic value of LysoPC (20:0) and LysoPC (P-16:0) by receiver operating characteristic (ROC) curve analysis, providing evidence for their remarkable value as prognostic biomarkers for predicting SFTS clinical outcomes. In particular, LysoPC (20:0) and LysoPC (P-16:0), along with APTT, yielded superior prognostic performance for fatal SFTS [area under the curve (AUC) = 98.4%], outperforming routine clinical parameters. Collectively, our findings revealed the lipidomic landscape after SFTSV infection, which offers new insights into the mechanisms of SFTS disease progression and suggests that targeting lipid metabolism may serve as a potential therapeutic strategy.

Importance: This study systematically investigated the lipid landscape profile of SFTS-infected patients with different clinical outcomes. Our results revealed a global alteration in the lipid signature, particularly the glycerophospholipid metabolic pathway, induced by SFTSV infection. Notably, LysoPC (20:0) and LysoPC (P-16:0) presented remarkable prognostic value as novel biomarkers for SFTSV infection and may contribute to the prognosis of SFTS progression and appropriate interventions.