Introduction: Sepsis is a life-threatening organ dysfunction caused by infection and is a common postsurgical complication. Despite the discovery of numerous biomarkers of sepsis, only a few are utilized in clinical practice due to limited diagnostic specificity and prognostic utility. Soluble Suppression of Tumorigenicity 2 (sST2), a decoy receptor in the IL-33/ST2 pathway, has been emerging as a potential biomarker of sepsis with relevance to immune modulation and tissue injury; however, the findings across studies have been diverse. This study aimed to systematically review the literature published in this context and perform a meta-analysis to obtain the pooled results of the diagnostic and prognostic utility of sST2 in sepsis. Methods: The databases PubMed, Scopus, and Web of Science were searched for studies published up to 20 July 2025. Risk of bias was assessed using the ROBINS-I tool for non-randomized studies. Data on study characteristics, patient demographics, sST2 levels in sepsis cases, controls, survivors and non-survivors, and predictability were extracted. Meta-analysis was performed using RevMan to determine differences in sST2 levels across sepsis cases and controls, as well as survivors and non-survivors. Pooled estimates were expressed as standardized mean differences (SMD) using a random-effects model. Sensitivity analysis was conducted to investigate the influence of each study on the pooled estimate and overall heterogeneity. Results: Thirteen studies were included, and we found significantly higher sST2 levels in sepsis cases as compared to controls (SMD = 1.42, 95% CI: 0.97–1.87, P < 0.00001, I 2 = 89%). Sepsis survivors had significantly lower sST2 levels than non-survivors (SMD = −0.79, 95% CI: −1.23 to −0.35, P = 0.0004, I 2 = 87%). Significant heterogeneity (I 2 : 89% and 87%) observed in the analyses was suggestive of substantial clinical and methodological differences between studies. Sensitivity analysis demonstrated no changes in the statistical significance when each study was excluded one at a time, indicating a consistent direction of association. Conclusion: sST2 is significantly elevated in sepsis and is associated with survival. Our findings highlight sST2 as a promising adjunct biomarker for the early detection and prognostication of sepsis, with potential relevance that warrants targeted investigation in perioperative and surgical populations. Despite the consistent direction of association, the magnitude of the pooled estimates should be cautiously interpreted due to high heterogeneity.
Bhattarai et al. (Fri,) studied this question.