Tianyan Chen,1,* Yawen Liu,2,* Yuan Liu,1 Nannan Hu,1 Yan Dai,1 Chuanlong Zhu,1 Yaping Han,1 Ke Jin,1 Jun Li1 

1Department of Infectious Disease, the First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Clinical Medical Engineering, the First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun Li; Ke Jin, Department of Infectious Disease, the First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Email dr-lijun@vip.sina.com; penghaoren2001@126.com

Purpose: Hyperactive immune responses in severe fever with thrombocytopenia syndrome (SFTS) is considered to associated with disease severity, prognosis and complications. This article aims to evaluate the validity of complement C3a, C5a, and sC5b-9 in predicting the severity and clinical outcomes in SFTS.
Patients and Methods: Patients diagnosed with SFTS at the First Affiliated Hospital with Nanjing Medical University from March to November 2021 were enrolled in this retrospective analysis. The study evaluated C3a, C5a, and sC5b-9 levels between SFTS patients and healthy controls. The diagnostic and prognostic efficiency of C3a, C5a, and sC5b-9 for SFTS was assessed utilizing receiver operating characteristic (ROC) curve analysis. Correlation analysis was performed to examine the relationships between these complement components and clinical laboratory parameters in SFTS patients.
Results: A total of 67 hospitalized SFTS patients were enrolled. SFTS patients exhibited significantly higher concentrations of C3a, C5a, and sC5b-9 compared to healthy controls. Non-survival and severe SFTS patients had notably higher C3a and sC5b-9 levels than survival and mild, respectively. ROC curve analysis revealed that C3a and sC5b-9 demonstrated effective performance for distinguishing severity in SFTS patients, with the area under the curve (AUC) of 0.784 (95% CI: 0.671– 0.896, p < 0.001) and 0.703 (95% CI: 0.573– 0.832, p = 0.005), respectively. The correlation analysis indicated that C3a and sC5b-9 positively correlated with SFTS RNA, CRP, PCT, ALT, AST, ALP, LDH, CK, HBDH, APPT, TT and D-dimer, while C3a negatively correlated with PLT.
Conclusion: This study revealed abnormalities in complement components among patients with SFTS. C3a and sC5b-9 levels show promise as biomarkers for linking with disease severity and prognosis, potentially providing therapeutic targets for the management of SFTS patients and guide future mechanistic research.

Keywords: severe fever with thrombocytopenia syndrome, complement anaphylatoxins, sC5b-9, risk factors