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

Abstract

Background: Endothelial activation and stress index (EASIX) reflects endothelial dysfunctionor 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 evaluatethe clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality incritically ill patients with COVID-19 in South Korea. Methods: Secondary analysis was performed using clinical data retrospectively collectedfrom 22 nationwide hospitals in South Korea between January 1, 2020, andAugust 31, 2021. Patients were at least 19 years old and admitted to the ICU for severeCOVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactatedehydrogenase (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 yearswith 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±1.52vs. 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 betterarea under the receiver operating characteristic curve than of the sequential organ failureassessment (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 betterdiscriminatory ability than the SOFA score in predicting ICU mortality.