{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:27:59Z","timestamp":1791232079109,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019s test were used to evaluate the robustness of the findings and possible small-study effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u00a0=\u00a02.08, 95% CI: 1.40-2.76; P&amp;lt;0.01). Substantial heterogeneity was observed (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a094%, P&amp;lt;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\u2019s 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\n                      <jats:italic>post hoc<\/jats:italic>\n                      , 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420251149587.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1903694","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:22:35Z","timestamp":1786076555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum interleukin-10 levels and mortality in severe fever with thrombocytopenia syndrome: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanan","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University","place":["Zhenjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zanzan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University","place":["Zhenjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University","place":["Zhenjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University","place":["Zhenjiang, China"]},{"name":"Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(14)70718-2","article-title":"Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis","volume":"14","author":"Liu","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1010095","article-title":"Fever with thrombocytopenia associated with a novel bunyavirus in China","volume":"364","author":"Yu","year":"2011","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3201\/eid2505.181463","article-title":"Endemic severe fever with thrombocytopenia syndrome, 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