EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Thomas Luft, Clemens-Martin Wendtner, Florentina Kosely, Aleksandar Radujkovic, Axel Benner, Felix Korell, Lars Kihm, Matthias F Bauer, Peter Dreger, Uta Merle, Thomas Luft, Clemens-Martin Wendtner, Florentina Kosely, Aleksandar Radujkovic, Axel Benner, Felix Korell, Lars Kihm, Matthias F Bauer, Peter Dreger, Uta Merle

Abstract

Background: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19.

Methods: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions.

Results: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha.

Conclusion: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.

Keywords: EASIX; SARS-CoV2 (COVID- 19); angiopoietin-2 (Ang-2); endothelial activation and stress index; prediction of outcome; soluble thrombomodulin; suppressor of tumorigenicity 2 (ST2).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Luft, Wendtner, Kosely, Radujkovic, Benner, Korell, Kihm, Bauer, Dreger and Merle.

Figures

Figure 1
Figure 1
Outcome of COVID-19 patients according to EASIX. Outcome of COVID-19 patients according to EASIX (cut-off 2) in the training cohort (left panels) and the validation cohort (right panels). (A) Cumulative incidence of severe courses of disease (mechanical ventilation and/or death, V/D). (B) Kaplan-Meier plots of overall survival.
Figure 2
Figure 2
Endothelial markers and EASIX. Boxplots of serum levels of endothelial markers according to the EASIX cut-off: angiopoietin-2 (ANG2), suppressor of tumorigenicity-2 (ST2), soluble thrombomodulin (sTM), CXCL8 (interleukin-8), CXCL9 (monokine induced by gamma interferon, MIG), interleukin-18 (IL18) and IL18 binding protein A (IL18BPa). P-values for Kruskal-Wallis tests, n=87. Spearman-rho correlation coefficients with EASIX as continuous variable (n=87): ANG2 0.355, p

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