Kinetics of viral load and cytokines in severe fever with thrombocytopenia syndrome

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Japan, and Korea, which is characterized by high fever, thrombocytopenia, and high mortality. It is hypothesized that a cytokine storm plays an important role in the pathophysiology of SFTS. However, limited data have been published on the detailed kinetics of the viral load and cytokine profiles throughout the course of this disease. Objectives: We investigated the patterns of changes in cytokines and viral load in SFTS patients. Study design: During the admission period of patients, RNA was extracted from plasma and quantified by reverse transcription polymerase chain reaction. In addition, cytokine bead arrays were performed for the 18 cytokines and chemokines selected for testing. Results: The median time from admission to the negative conversion of SFTS viremia was 17.0 days. When censored patients were found to be negative for viral load at discharge, the median duration of viral shedding was 13.0 days (95% CI, 5.4-20.6). Interferon (IFN)-alpha, interleukin (IL)-10, and IFN-gamma-induced protein (IP)-10 concentrations significantly increased in the early course of disease and then decreased during the hospital stay. However, the concentrations of tumor necrosis factor-alpha, IL-1 beta, IL-12p40, IL-13, IL-17A, Regulated on Activation and Normally T-cell Expressed and Secreted (RANTES), and vascular endothelial growth factor (VEGF) increased during the late course of disease. Initial IP-10 levels during hospital days 1-4 were the most significantly correlated with initial viral load (r = 0.88, P < .01). Conclusion: SFTS viremia persisted until weeks 2-3 and was highly correlated with initial plasma IP-10 levels. In addition, IFN-alpha, IL-10, and IP-10 were associated with the initial cytokine storm in SFTS.