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

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 o...

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Published in:	Frontiers in immunology Vol. 12; p. 634416
Main Authors:	Luft, Thomas, Wendtner, Clemens-Martin, Kosely, Florentina, Radujkovic, Aleksandar, Benner, Axel, Korell, Felix, Kihm, Lars, Bauer, Matthias F., Dreger, Peter, Merle, Uta
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 23.06.2021
Subjects:	Adolescent Adult Aged Aged, 80 and over angiopoietin-2 (Ang-2) Biomarkers - metabolism COVID-19 - diagnosis COVID-19 - mortality EASIX endothelial activation and stress index Endothelial Cells - physiology Female Hematopoietic Stem Cell Transplantation Hospitalization Humans Immunology Male Middle Aged Prognosis Prospective Studies Respiration, Artificial SARS-CoV-2 - physiology SARS-CoV2 (COVID- 19) Severity of Illness Index soluble thrombomodulin suppressor of tumorigenicity 2 (ST2) Survival Analysis Transplantation, Homologous Treatment Outcome Young Adult angiopoietin-2 (Ang-2) soluble thrombomodulin prediction of outcome endothelial activation and stress index suppressor of tumorigenicity 2 (ST2) EASIX SARS-CoV2 (COVID- 19)
ISSN:	1664-3224, 1664-3224
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Abstract	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. 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. 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. EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.
AbstractList	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.BACKGROUNDThe 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.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.METHODSSARS-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.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.RESULTSEASIX 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.EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.CONCLUSIONEASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance. 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. 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. 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. EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance. BackgroundThe 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.MethodsSARS-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.ResultsEASIX 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.ConclusionEASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.
Author	Benner, Axel Bauer, Matthias F. Dreger, Peter Kosely, Florentina Wendtner, Clemens-Martin Radujkovic, Aleksandar Luft, Thomas Merle, Uta Korell, Felix Kihm, Lars
AuthorAffiliation	2 Munich Clinic Schwabing, Academic Teaching Hospital, Ludwig-Maximilians University (LMU) , Munich , Germany 7 Department of Internal Medicine IV, University of Heidelberg , Heidelberg , Germany 1 Department of Internal Medicine V, University of Heidelberg , Heidelberg , Germany 4 Division of Biostatistics, German Cancer Research Center , Heidelberg , Germany 6 Institute of Laboratory Diagnostics, Hygiene and Transfusion Medicine, Hospital Ludwigshafen , Ludwigshafen , Germany 3 Medical Department B, Hospital Ludwigshafen , Ludwigshafen , Germany 5 Department of Internal Medicine I, University of Heidelberg , Heidelberg , Germany
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Copyright	Copyright © 2021 Luft, Wendtner, Kosely, Radujkovic, Benner, Korell, Kihm, Bauer, Dreger and Merle. Copyright © 2021 Luft, Wendtner, Kosely, Radujkovic, Benner, Korell, Kihm, Bauer, Dreger and Merle 2021 Luft, Wendtner, Kosely, Radujkovic, Benner, Korell, Kihm, Bauer, Dreger and Merle
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Keywords	angiopoietin-2 (Ang-2) soluble thrombomodulin prediction of outcome endothelial activation and stress index suppressor of tumorigenicity 2 (ST2) EASIX SARS-CoV2 (COVID- 19)
Language	English
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Helena Stabile, Sapienza University of Rome, Italy This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology Reviewed by: Saikat Majumder, University of Pittsburgh, United States; Tatiani Uceli Maioli, Federal University of Minas Gerais, Brazil
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Snippet	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... BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that...
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SubjectTerms	Adolescent Adult Aged Aged, 80 and over angiopoietin-2 (Ang-2) Biomarkers - metabolism COVID-19 - diagnosis COVID-19 - mortality EASIX endothelial activation and stress index Endothelial Cells - physiology Female Hematopoietic Stem Cell Transplantation Hospitalization Humans Immunology Male Middle Aged Prognosis Prospective Studies Respiration, Artificial SARS-CoV-2 - physiology SARS-CoV2 (COVID- 19) Severity of Illness Index soluble thrombomodulin suppressor of tumorigenicity 2 (ST2) Survival Analysis Transplantation, Homologous Treatment Outcome Young Adult
Title	EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients
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