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

Oindrila Paul (Department of Physiology), JianQin Tao (University of Pennsylvania), Evgenia Arguiri (University of Pennsylvania), Melpo Christofidou-Solomidou (University of Pennsylvania), Nikita Jain (Department of Physiology), Shampa Chatterjee (University of Pennsylvania)

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.

NIHR56HL139559