Endothelial Dysfunction and Thrombosis in Patients With COVID-19—Brief Report

Abstract

Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff’s efforts to avoid fatal outcomes. One of the health professionals’ goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management

“…10 It has been suggested that the virus instigates the process of pyroptosis , an inflammatory form of programmed cell death observed upon infection with intracellular pathogens, which could contribute to the endothelial cell death after COVID-19 infection and could increase proinflammatory cytokine releases, such as interleukin (IL)-1 beta and IL-18. 11 Both these pathologic processes of endothelial dysfunction and pyroptosis might lead to systemic thrombotic events. 11 Monitoring of coagulation indices in severely ill COVID-19 patients seems imperative to identify those patients at increased thromboembolic risk and to adjust thromboprophylaxis accordingly.…”

“…11 Both these pathologic processes of endothelial dysfunction and pyroptosis might lead to systemic thrombotic events. 11 Monitoring of coagulation indices in severely ill COVID-19 patients seems imperative to identify those patients at increased thromboembolic risk and to adjust thromboprophylaxis accordingly.…”

Thrombosis and Coagulopathy in COVID-19: Current Understanding and Implications for Antithrombotic Treatment in Patients Treated With Percutaneous Coronary Intervention

“…Endothelial dysfunction induces inflammation and vascular remodeling ( 38 ), which are associated with severe COVID-19. Endotheliopathy or endothelial dysfunction, including endothelial activation, endotheliitis, and thrombotic events, is an indicator of coagulopathy in COVID-19 patients ( 33 , 34 , 39 ).…”

“…Upregulation of vascular endothelial growth factor and downregulation of E-cadherin expression enhance the permeability of endothelial cells in COVID-19 patients ( 41 ). In addition, biopsy of lung tissues of COVID-19 patients shows upregulation of interleukin-6 (IL-6), tumor necrosis factor-α, intercellular adhesion molecule-1, and caspase-1 expression ( 39 ). Further, quantitative analysis showed a significant increase in expression levels of von Willebrand factor antigen and soluble P-selectin, which are markers of endothelial cell and platelet activation, in COVID-19 patients admitted to intensive care units ( 34 ).…”

COVID-19 and vascular disorders (literature review)

“…При иммуногистохимическом исследовании посмертных препаратов легких пациентов, умерших от SARS-CoV-2-инфекции, было выявлено повышение экспрессии маркеров эндотелиальной дисфункциимолекулы межклеточной адгезии 1-го типа (ICAM-1) и каспазы-1. Авторы [41] связывают экспрессию молекулы ICAM-1 с формированием стойкого эндотелиита. Активация каспазы-1 с высвобождением провоспалительных цитокинов играет важную роль в механизмах развития пироптоза, который ведет к фрагментации эндотелиоцитов и их гибели.…”