Pulmonary Endothelial Activation with COVID-19: Possible Role of Reactive Oxygen Species

ABSTRACT

Introduction Recent research suggests that endothelial activation plays a role in COVID-19 pathogenesis by promoting a pro-coagulative and pro-inflammatory state. However, the mechanism by which the endothelium is activated in COVID-19 is unclear. Objective To investigate the mechanism by which COVID-19 activates the pulmonary endothelium. Hypothesis The pulmonary endothelium generates reactive oxygen species (ROS) upon exposure to the ?inflammatory load? of the systemic circulation. Methods COVID-19 was recreated in vitro and ex vivo, by exposing human lung endothelial cells (EC) or donor human lung slices (human precision-cut lung slices or huPCLS) to medium supplemented with serum from COVID-19 affected subjects. Sera were acquired from patients with COVID-19 infection admitted to the Intensive Care Unit of the Hospital at the University of Pennsylvania. ROS (fluorescent dye, CellROX) and intercellular adhesion molecule (ICAM-1) levels were assessed by fluorescence labeling and imaging. Results Both EC activation (as monitored by ROS production) and pro-inflammatory phenotype (as assessed by ICAM-1), were significantly higher with COVID-19 as compared to normal subjects. Conclusions The endothelium is activated with COVID-19 via ROS production;thus, the ROS produced drive a pro-inflammatory phenotype by inducing the expression of ICAM-1, a pivotal marker of endothelium inflammation. As ROS mediates EC activation and inflammation during COVID-19, ROS blockade could be a therapeutic target in maintaining vascular health.