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Core biomarkers and early detection criteria of cytokine storm triggered by infectious diseases: A systematic review
Junyu Yin1, Xianxu Huang1, Xin Ou1
1Center of Clinical Epidemiology and Biobank, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
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 (23-40 pg/mL), IL-10 (57 pg/mL), CRP (46-100 mg/L), serum ferritin (250-1000 ng/mL), and D-dimer (1.5-4.9 μg/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 analyzes confirmed the robustness of these findings, with moderate heterogeneity observed for CRP (I²=70.9%). IL-6 (23-40 pg/mL) and IL-10 (57 pg/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.
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