Role of endothelium activation biomarkers in prediction COVID-19 related intra-Hospital Mortality

ABSTRACT

Background: Endothelial damage and hypercoagulability are major players behind the hemostatic derangement in SARS-CoV-2 infection. Aims: In this prospective cohort study of COVID-19 patients, we aimed to assess the role of circulating endothelial activation/damage biomarkers in predicting in-hospital mortality. Methods: Clinical data of 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 analyzed. 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, 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 Ddimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). Patients with a moderate and severe ARDS (i.e. PaO2/FiO2 ≤200%) have considerably higher vWF and sTM levels, and lower t-PA/PAI-1 values compared to patients in the mild ARDS group (i.e. PaO2/FiO2 >200%). 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, we generated a linear score with 3-risk groups (AUC 0.903) that provided a cumulative incidence of death of 0 % in the low-, 32% in the intermediate-, and 78% in the high-risk group ( P < 0.001). Conclusions: In conclusion, our study provides an extensive overview of the endothelial damage induced by SARSCoV-2 infection in hospitalized patients with virus-induced pneumonia and different degrees of disease severity. In addition, despite the small sample size and the need for the external validation, we could generate an accurate score based on circulating vWF to predicting mortality in severe COVID-19 patients.