Core Biomarkers and Early Detection Criteria of Cytokine Storm Triggered by Infectious Diseases: A Systematic Review and Meta Analysis.

OBJECTIVE: Cytokine storm (CS) is a critical immunopathological mechanism contributing to disease severity, organ failure, and mortality in infectious diseases. However, standardized clinical diagnostic criteria, particularly for early-stage CS, remain lacking. This systematic review and meta-analysis aimed to identify core diagnostic biomarkers and summarize early detection criteria for CS. METHODS: PubMed, Scopus, Embase, and the Cochrane Library were searched for eligible studies published between 2001 and 2025. Study selection, quality assessment, and data extraction were conducted according to predefined criteria. RESULTS: 15 studies were included. Interleukin-6 (IL-6), Interleukin-10 (IL-10), C-reactive protein (CRP), serum ferritin and D-dimer were identified as core biomarkers of CS. Eight studies proposed quantitative diagnostic thresholds, including IL-6 (23-40pg/mL), IL-10 (57pg/mL), CRP (46-100mg/L), serum ferritin (250-1000ng/mL), and D-dimer (1.5-4.9μg/mL), while nine studies relied on qualitative biomarker changes and/or clinical manifestations. Meta-analysis demonstrated that elevated levels of IL-6 (OR=11.43), CRP (OR=4.85), serum ferritin (OR=9.61), D-dimer (OR=4.60), and IL-10 (OR=7.97) were significantly associated with increased in-hospital mortality. Subgroup and sensitivity analyses confirmed the robustness of these findings, with moderate heterogeneity observed for CRP (I²=70.9%). IL-6 (23-40pg/mL) and IL-10 (57pg/mL) may serve as potential early detection criteria for CS. CONCLUSION: IL-6, IL-10, serum ferritin, CRP, and D-dimer represent core diagnostic biomarkers of CS and are significantly associated with increased in-hospital mortality in infectious diseases.