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 (23-40 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.