Cytokine Indicators Associated with Disease Severity in Severe Fever with Thrombocytopenia Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVE

The purpose of this study is to study cytokine indicators for the identification of severe fever with thrombocytopenia syndrome (SFTS) severity.

METHODS

We searched the literature in PubMed, Embase, and Web of Science published before 7 April 2026. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed.

RESULTS

A total of 22 articles were eventually included in our study. Our findings demonstrate that circulating concentrations of Interleukin-6 (IL-6) (SMD = 2.02, 95% CI: 1.53-2.51, I2 = 95.2%), Interleukin-10 (IL-10) (SMD = 1.18, 95% CI: 0.92-1.44, I2 = 71.3%), Interleukin-8 (IL-8) (SMD = 0.91, 95% CI: 0.61-1.20, I2 = 69%), Tumor necrosis factor-alpha (TNF-α) (SMD = 0.70, 95% CI: 0.43-0.96, I2 = 64.6%), Interferon-gamma (IFN-γ) (SMD = 1.32, 95% CI: 0.69-1.95, I2 = 89.1%), Interleukin-1 beta (IL-1β) (SMD = 1.78, 95% CI: 0.85-2.71, I2 = 94.8%), Monocyte chemoattractant protein-1 (MCP-1) (SMD = 1.15, 95% CI: 0.80-1.50, I2 = 46.1%), Interferon-alpha (IFN-α) (SMD = 1.53, 95% CI: 0.38-2.68, I2 = 89.6%), Granulocyte Colony-Stimulating Factor (G-CSF) (SMD = 1.79, 95% CI: 0.99-2.59, I2 = 68.1%) and Inducible protein 10 (IP-10) (SMD = 1.11, 95% CI: 0.60-1.62, I2 = 58.3%) are significantly elevated in patients with severe SFTS compared with those with mild disease, whereas Transforming Growth Factor-beta (TGF-β) (SMD = -0.51, 95% CI: -0.78--0.24, I2 = 6.0%) and RANTES (SMD = -0.10, 95% CI: -0.40-0.20, I2 = 0.0%) levels are reduced in the severe group.

CONCLUSIONS

By analyzing the cytokine indicators of SFTS patients, we have found some indicators that are representative of SFTS severity. Our findings provide a clinically actionable basis for early severity prediction and further useful evidence for clinicians to manage severe patients efficiently.