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Could Targeting Endothelial Cells Diminish COVID-19 Symptoms?

TARGETING endothelial cells in patients with coronavirus disease (COVID-19) with severe lung disease may provide a novel approach to restoring normal lung function, according to a recent study from Stony Brook University, Stony Brook, New York, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) receptors to infect and damage epithelial cells in the upper respiratory track. Within alveoli, the tiny air sacs in the lung, oxygen and carbon dioxide molecules are exchanged to and from the bloodstream across an epithelial–endothelial barrier. However, the process by which SARS-CoV-2 dysregulates vascular function causing an acute respiratory distress syndrome in COVID-19 patients remains to be solved.

Led by microbiology and immunology researcher, Prof Erich Mackow, the team investigated this mechanism by analysing SARS-CoV-2 infection in human endothelial cells of COVID-19 patients from the lung, heart, kidney, and brain. Prof Mackow noted: “Our research revealed that endothelial cells lack ACE2 receptors and that endothelial cells were only SARS-CoV-2 infected after expressing ACE2 receptors in them. Since endothelial cell functions are dysregulated by SARS-CoV-2, these findings suggest a novel mechanism of regulation that does not require viral infection.”

These findings suggest that the endothelium is indirectly activated, potentially due to surrounding tissue damage, and provide a basis for further research to therapeutically target and restore normal endothelial cell function. The team’s research also focussed on endothelial cells and ACE2 functions in COVID-19 to assess the mechanisms of capillary inflammation and clotting within vessels. Commenting on the findings, Prof Mackow added: “If endothelial cells are not infected or directly damaged, they can still direct inflammation and clotting by just being activated.”

This research highlights the potential to therapeutically target the activation of the endothelium to resolve coagulation and inflammatory COVID-19 symptoms. Moving forward, the team is also investigating how endothelial cells are activated by SARS-CoV-2 or in response to other SARS-CoV-2 infected lung cells that express ACE2.