Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction

Marina Marchetti; Patricia Gomez-Rosas; Eleonora Sanga; Sara Gamba; Cristina Verzeroli; Laura Russo; Francesco Restuccia; Francesca Schieppati; Ezio Bonanomi; Marco Rizzi; Stefano Fagiuoli; Andrea D'Alessio; Luca Lorini; Anna Falanga

doi:10.1055/s-0041-1731711

TH Open, Table of Contents

CC BY 4.0 · TH Open 2021; 05(03): e253-e263
DOI: 10.1055/s-0041-1731711

Original Article

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction

Marina Marchetti

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Patricia Gomez-Rosas

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

²Hematology Service, Hospital General Regional Tecamac IMSS, Mexico, Mexico

,

Eleonora Sanga

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Sara Gamba

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Cristina Verzeroli

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Laura Russo

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Francesco Restuccia

³Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Francesca Schieppati

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Ezio Bonanomi

³Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Marco Rizzi

⁴Unit of Infectious Diseases, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Stefano Fagiuoli

⁵Department of Internal Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Andrea D'Alessio

⁶Department of Medical Oncology and Internal Medicine, Policlinico San Marco, Zingonia, Bergamo, Italy

,

Luca Lorini

³Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

,

Anna Falanga

¹Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy

⁷School of Medicine, University of Milano Bicocca, Milano, Italy

› Author Affiliations

Abstract

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection.

Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality.

Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed.

Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group.

Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.

Keywords

endothelium - COVID-19 - von willebrand factor - hypercoagulation

Full Text

References

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