Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19
| Autor: | Antoine Rauch, Guillaume Lefèvre, Alain Duhamel, Anne Bauters, Eric Kipnis, Natacha Rousse, Senna Staessens, Pauline Varlet, Sophie Susen, Annabelle Dupont, Julien Labreuche, Bart Staels, Morgan Caplan, Flavien Vincent, Julien Poissy, Marc Lambert, Mickael Rosa, Mouhamed Moussa, Simon F. De Meyer, Julien Goutay, Karine Faure, Fanny Lassalle, Delphine Corseaux, Delphine Garrigue, Emmanuelle Jeanpierre, Peter J. Lenting |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Endothelium Critical Care Multiple Organ Failure 030204 cardiovascular system & hematology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor medicine Humans Complement Activation Liver injury business.industry SARS-CoV-2 Microcirculation COVID-19 Thrombosis Neutrophil extracellular traps Immune dysregulation Liver Failure Acute Middle Aged medicine.disease Complement system Nucleosomes 030104 developmental biology medicine.anatomical_structure Respiratory failure Cytokines Tumor necrosis factor alpha Female Endothelium Vascular Cardiology and Cardiovascular Medicine business Respiratory Insufficiency Biomarkers |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 41(5) |
| ISSN: | 1524-4636 |
| Popis: | Objective: Whether endotheliopathy only mirrors coronavirus disease 2019 (COVID-19) severity or plays an intrinsic role in microvascular thrombosis and organ failure remains unanswered. We assessed whether markers of endothelial damage and immune dysregulation were associated with organ failure, thrombus formation, and death. Approach and Results: Markers of endothelial damage (VWF:Ag [von Willebrand factor antigen], PAI-1 [plasminogen activator inhibitor-1], syndecan-1, TFPI [tissue factor pathway inhibitor], and soluble thrombomodulin), complement activation (C5a and C5b-9), cytokines (IL [interleukin]-6, TNF [tumor necrosis factor]-α, and IL-2R), and neutrophil extracellular traps (cell-free DNA, nucleosomes, and myeloperoxidase-DNA) were measured at intensive care unit admission in 82 patients with COVID-19. We also analyzed the histological composition of thrombi collected in critically ill living patients successfully weaned from extracorporeal membrane oxygenation. Beside respiratory failure, VWF:Ag, PAI-1, TFPI, and syndecan-1 were independently associated with liver injury and multiorgan failure development, underlining the direct role of endotheliopathy in organ failure. Nucleosomes were also associated with liver injury, multiorgan failure, and death which occurred in 38%, 60%, and 27% of patients, respectively. Moreover, dysregulated immune response including cytokines, complement, and neutrophil extracellular traps was associated with markers of endothelial damage, respiratory failure, and liver injury. COVID-19 thrombi retrieved from extracorporeal membrane oxygenation circuitry contained accumulation of neutrophils, VWF, and significantly higher amount of neutrophil extracellular traps when compared with non-COVID-19 thrombi. Conclusions: We provide new associative data supporting that endotheliopathy and dysregulated immune responses are involved in respiratory and liver failure through microvascular damage in patients with severe COVID-19. |
| Databáze: | OpenAIRE |
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