Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
PLoS One. 2022 May 19;17(5):e0268296. doi: 10.1371/journal.pone.0268296. eCollection 2022.
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.
严重的 2019 冠状病毒病（COVID-19）的特征是血管炎症和血栓形成。我们和其他人已经提出，冠状病毒感染的炎症反应会激活内皮细胞，导致内皮细胞释放促血栓蛋白。这些介质可引发肺微血管阻塞，导致氧合恶化、急性呼吸窘迫综合征和死亡。在目前的研究中，我们测试了这样一个假设，即来自内皮细胞的生物标志物水平越高，与 COVID-19 患者的氧合越差相关。我们研究了 83 名年龄在 18 至 84 岁之间的 COVID-19 患者，他们都入住了一家单中心医院。通过氧需求对肺病的严重程度进行分类，包括不需要氧气、低流量氧气、高流量鼻导管氧气、机械通气和死亡。我们测量了两种由激活的内皮细胞释放的蛋白，即血管性血友病因子（VWF）抗原和可溶性 P 选择素（sP-Sel），以及一种全身性血栓形成的生物标志物，D-二聚体。此外，我们还探讨了内皮生物标志物水平与促炎细胞因子和趋化因子以及血管炎症生物标志物水平之间的关联。我们发现，在 COVID-19 肺病更严重的个体中，VWF、sP-sel 和 D-二聚体的水平增加。内皮细胞激活的生物标志物也与促炎细胞因子和趋化因子相关。总之，我们的数据表明，VWF 和 sP 选择素的水平升高与 COVID-19 肺病的严重程度相关，并与炎症和血管炎症的生物标志物相关。我们的数据支持这样一种概念，即 COVID-19 是一种血管疾病，涉及到炎症状态下的内皮损伤。
