Association between Age-Adjusted Endothelial Activation and Stress Index and Intensive Care Unit Mortality in Patients with Severe COVID-19

Background: Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea.Methods: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (10⁹ cells/L)] and age-EASIX (EASIX×age) were calculated and log₂-transformed.Results: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log₂ age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log₂ age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p<0.001). log₂ age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001).Conclusion: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.