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.

Keywords: COVID-19; coronavirus; pandemics; pyroptosis; thrombosis.

Figure.

Graphs showing the comparison between the coronavirus disease 2019 (COVID-19), H1N1, and control groups regarding TNF (tumor necrosis factor)-α, IL (interleukin)-6, ICAM-1 (intercellular adhesion molecule 1); in percentage per high-power fields (HPF), and caspase-1 tissue expression (in Allred score). TNF-α is remarkably high in the alveolar septal cells (black arrowheads) and the alveolar-capillary cells (black arrows) of the COVID-19 case than in the H1N1 case. Alveolar lumens are identified with asterisks. IL-6 tissue expression is remarkably high in the endothelial cells (black arrows) of the COVID-19 case than in the H1N1 case. ICAM-1 tissue expression is remarkably higher in the endothelial cells (black arrows) of the COVID-19 case than in the H1N1 case. Caspase-1 is higher in the endothelial cells of the COVID-19 case than in the H1N1 case. Kruskal-Wallis test was used for P values. Scale bars=50 µm.