Plasma copper and endothelial injury markers in sepsis: A prospective observational study

Endothelial injury is central to sepsis, and altered copper homeostasis may be involved in inflammatory and oxidative stress responses. This study examined the association between plasma copper (Cu) concentrations, endothelial injury markers, inflammatory burden, illness severity, and 28-day mortality in patients with sepsis.

This prospective observational study enrolled 100 ICU patients with sepsis between March and December 2025. Patients were classified as survivors or non-survivors according to 28-day outcomes. Plasma Cu, VE-cadherin, and Syndecan-1 (SDC-1) were measured within 24 h of admission. Correlation, logistic regression, receiver operating characteristic (ROC), and sensitivity analyses were performed.

Plasma Cu concentrations were markedly elevated in non-survivors compared to survivors. Non-survivors also exhibited higher plasma VE-cadherin and SDC-1 levels. Plasma Cu was positively correlated with VE-cadherin, SDC-1, APACHE II score, SOFA score, PCT, and CRP. The correlations between Cu and PCT or CRP were weak. Plasma Cu showed moderate discriminatory ability for 28-day mortality, whereas PCT and CRP did not show discriminatory ability in this cohort. In multivariable logistic regression and sensitivity analyses, plasma Cu was not independently associated with 28-day mortality after adjustment for illness severity, lactate, or inflammatory burden.

Plasma Cu was associated with endothelial injury markers, inflammatory markers, illness severity, and 28-day mortality in patients with sepsis. However, Cu was not an independent predictor of mortality after adjustment. These findings suggest that plasma Cu may reflect an inflammation-related endothelial injury and severity phenotype rather than serve as a stand-alone prognostic biomarker.