tetano
Editor, Senior Moderator
PLoS One
. 2022 May 19;17(5):e0268296.
doi: 10.1371/journal.pone.0268296. eCollection 2022.
Markers of endothelial cell activation are associated with the severity of pulmonary disease in COVID-19
William O Osburn[SUP] 1 [/SUP], Kimberly Smith[SUP] 1 [/SUP], Lisa Yanek[SUP] 2 [/SUP], Nuria Amat-Alcaron[SUP] 1 [/SUP], David R Thiemann[SUP] 1 [/SUP], Andrea L Cox[SUP] 3 [/SUP], Thorsten M Leucker[SUP] 1 [/SUP], Charles J Lowenstein[SUP] 1 [/SUP]
Affiliations
Abstract
Severe coronavirus disease-19 (COVID-19) is characterized by vascular inflammation and thrombosis. We and others have proposed that the inflammatory response to coronavirus infection activates endothelial cells, leading to endothelial release of pro-thrombotic proteins. These mediators can trigger obstruction of the pulmonary microvasculature, leading to worsening oxygenation, acute respiratory distress syndrome, and death. In the current study, we tested the hypothesis that higher levels of biomarkers released from endothelial cells are associated with worse oxygenation in patients with COVID-19. We studied 83 participants aged 18-84 years with COVID-19 admitted to a single center. The severity of pulmonary disease was classified by oxygen requirement, including no oxygen requirement, low-flow oxygen, high-flow nasal cannula oxygen, mechanical ventilation, and death. We measured plasma levels of two proteins released by activated endothelial cells, von Willebrand Factor (VWF) antigen and soluble P-Selectin (sP-Sel), and a biomarker of systemic thrombosis, D-dimer. Additionally, we explored the association of endothelial biomarker levels with the levels of pro-inflammatory cytokine and chemokines, and vascular inflammation biomarkers. We found that levels of VWF, sP-sel, and D-dimer were increased in individuals with more severe COVID-19 pulmonary disease. Biomarkers of endothelial cell activation were also correlated with proinflammatory cytokines and chemokines. Taken together, our data demonstrate increased levels of VWF and sP-selectin are linked to the severity of lung disease in COVID-19 and correlated with biomarkers of inflammation and vascular inflammation. Our data support the concept that COVID-19 is a vascular disease which involves endothelial injury in the context of an inflammatory state.
. 2022 May 19;17(5):e0268296.
doi: 10.1371/journal.pone.0268296. eCollection 2022.
Markers of endothelial cell activation are associated with the severity of pulmonary disease in COVID-19
William O Osburn[SUP] 1 [/SUP], Kimberly Smith[SUP] 1 [/SUP], Lisa Yanek[SUP] 2 [/SUP], Nuria Amat-Alcaron[SUP] 1 [/SUP], David R Thiemann[SUP] 1 [/SUP], Andrea L Cox[SUP] 3 [/SUP], Thorsten M Leucker[SUP] 1 [/SUP], Charles J Lowenstein[SUP] 1 [/SUP]
Affiliations
- PMID: 35588115
- DOI: 10.1371/journal.pone.0268296
Abstract
Severe coronavirus disease-19 (COVID-19) is characterized by vascular inflammation and thrombosis. We and others have proposed that the inflammatory response to coronavirus infection activates endothelial cells, leading to endothelial release of pro-thrombotic proteins. These mediators can trigger obstruction of the pulmonary microvasculature, leading to worsening oxygenation, acute respiratory distress syndrome, and death. In the current study, we tested the hypothesis that higher levels of biomarkers released from endothelial cells are associated with worse oxygenation in patients with COVID-19. We studied 83 participants aged 18-84 years with COVID-19 admitted to a single center. The severity of pulmonary disease was classified by oxygen requirement, including no oxygen requirement, low-flow oxygen, high-flow nasal cannula oxygen, mechanical ventilation, and death. We measured plasma levels of two proteins released by activated endothelial cells, von Willebrand Factor (VWF) antigen and soluble P-Selectin (sP-Sel), and a biomarker of systemic thrombosis, D-dimer. Additionally, we explored the association of endothelial biomarker levels with the levels of pro-inflammatory cytokine and chemokines, and vascular inflammation biomarkers. We found that levels of VWF, sP-sel, and D-dimer were increased in individuals with more severe COVID-19 pulmonary disease. Biomarkers of endothelial cell activation were also correlated with proinflammatory cytokines and chemokines. Taken together, our data demonstrate increased levels of VWF and sP-selectin are linked to the severity of lung disease in COVID-19 and correlated with biomarkers of inflammation and vascular inflammation. Our data support the concept that COVID-19 is a vascular disease which involves endothelial injury in the context of an inflammatory state.