Serum-soluble ST2 as a novel biomarker for COVID-19 severity and mortality: A systematic review and meta-analysis

Abstract

Introduction: While numerous biomarkers have demonstrated a link with the prognosis in patients with COVID-19, their practical applicability is constrained due to deficiencies in specificity, inadequate sensitivity, or a limited dynamic response. The objective of this systematic review and meta-analysis was to evaluate the role of the circulating soluble ST2 (sST2) levels as a predictive marker for the severity and mortality associated with COVID-19. Methods: A systematic search was conducted in PubMed/MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases until October 11, 2023 using well-defined search strategy. The occurrence of binary outcomes was determined through the computation of odds ratios (OR) with a 95% confidence interval (CI), employing the Mantel-Haenszel method. For continuous outcomes, the standard mean difference (SMD), along with a 95% CI, was the chosen metric. Pooled analysis was conducted using Stata version 17 (Stata Corp) and Review Manager v. 5.4 software (RevMan). The level of statistical significance was set at p < 0.05. Results: Nine studies, including 1732 patients, met the eligibility criteria. A pooled analysis across trials indicates that sST2 levels are remarkably elevated in COVID-19 patients compared to non-COVID-19 individuals (39.3±44.23 vs. 6.74±6.25; SMD= 3.52; 95%CI: 1.72 to 5.32), significantly higher in severe than non-severe cases (94.07±74.71 vs. 25.53±7.36; SMD=3.87; 95%CI: 2.69 to 5.05), and vary between survivors and non-survivors (43.18±21.54 vs. 119.11±113.98; SMD= -2.84; 95%CI: -4.49 to -1.19), with substantial differences in means and confidence intervals reported across these groups (p<0.001). Discussion: The evidence presented herein highlights sST2 as a promising biomarker for the assessment of COVID-19 severity and prognosis. Its correlation with mortality and severe disease phenotypes positions it as a potential target for therapeutic modulation and a candidate for inclusion in prognostic models.