Front Immunol. 2026 Aug 7;17:1903694. doi: 10.3389/fimmu.2026.1903694. eCollection 2026.
ABSTRACT
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, is an emerging tick-borne infectious disease associated with substantial case fatality and poses a considerable public health burden. Interleukin-10 (IL-10), an important anti-inflammatory and immunoregulatory cytokine, may reflect the magnitude of immune dysregulation in SFTS. This systematic review and meta-analysis primarily aimed to evaluate the association between serum IL-10 levels and mortality in patients with SFTSV infection. As a secondary exploratory objective, we assessed the threshold-based prognostic accuracy of IL-10 for fatal outcomes when sufficient data were available.
METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP were searched from database inception to October 11, 2025. Prospective and retrospective cohort studies, and case-control studies reporting serum IL-10 levels in survivors and non-survivors with laboratory-confirmed SFTSV infection were eligible. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale (NOS) and risk of bias using the Quality In Prognosis Studies (QUIPS) tool for studies on prognostic factors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool for studies contributing threshold-based prognostic accuracy data. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a prespecified random-effects model. Sensitivity analyses, subgroup analyses, meta-regression, funnel plots, and Egger’s test were used to evaluate the robustness of the findings and possible small-study effects.
RESULTS: Twelve studies involving 1,270 patients with SFTSV infection were included, comprising 290 non-survivors and 980 survivors. Serum IL-10 levels were significantly higher in non-survivors than in survivors (pooled SMD = 2.08, 95% CI: 1.40-2.76; P<0.01). Substantial heterogeneity was observed (I 2 = 94%, P<0.01), and the 95% prediction interval crossed zero. Sensitivity analyses generally preserved the direction of the association, including an analysis restricted to studies not requiring conversion from medians and quantiles; however, substantial residual heterogeneity and the limited number of directly reported datasets indicated considerable uncertainty regarding the magnitude of the pooled effect. Subgroup analyses according to study design showed a directionally consistent association, whereas exploratory meta-regression found no statistically significant relationship between study-level IL-10 concentration and effect size. Funnel-plot asymmetry and Egger’s regression test indicated possible small-study effects; however, the extreme between-study heterogeneity limited the ability to distinguish selective publication from methodological or clinical variability. Threshold-based prognostic-accuracy analyses suggested potential discriminatory value for mortality prediction, but they were based on only three studies using post hoc, non-validated cut-off values and therefore remained exploratory. The certainty of evidence for the association between IL-10 levels and mortality was rated as very low because of residual confounding, inconsistency, indirectness, and possible small-study effects.
CONCLUSION: Elevated serum IL-10 levels were associated with mortality in SFTS; however, the certainty of evidence was very low. IL-10 should therefore be considered a candidate prognostic biomarker requiring further prospective validation rather than a clinically established stand-alone prognostic tool.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251149587.
PMID:42630216 | PMC:PMC13493291 | DOI:10.3389/fimmu.2026.1903694
