Kurt Randall Stenmark, M.D.

Kurt Randall Stenmark, M.D.

Institution: University of Colorado Anschutz Medical Campus

Project: Role of hypoxia and complement in lung endothelial cell injury in COVID-19

Grant(s): COVID-19 Respiratory Virus Research Award

The lung disease caused by SARS-Cov2 is the main cause of death in patients with COVID-19. We will study whether the virus attack of lung endothelial cells in the smallest pulmonary blood vessels leads to activation of immune proteins called complement, and subsequent cell injury. It appears that in COVID-19, activated complement, which is usually beneficial against invading organisms, leads to endothelial cell injury. This in turn causes cell death, increased inflammation and clotting. We will test this hypothesis in studies using human lung endothelial cells in the small vessels of the lung infected by SARS-Cov2 and subjected to lack of oxygen (hypoxia), which is a frequent complication in COVID-19 patients. We will also use human lungs of patients who died of COVID-19 to show lung endothelial injury, evidence of virus infection, complement activation, and inflammation. These studies can lead to ways to minimize lung endothelial cell injury by COVID-19 and support blockade of complement to treat patients with lung disease due to COVID-19.

Update:

Much to our surprise, our extensive study of human lung microvascular endothelial cells in the lab does not support the hypothesis that the endothelial abnormalities (inflammation and coagulation) in COVID lung disease require or are the result of productive SARS-CoV-2 infection. Our results do however confirm an important enhancing effect of low oxygen on SARS-CoV-2 induced endothelial dysfunction. They suggest that targeting the complement system (part of the immune system that plays a crucial role in defense against common pathogens) appears to be a potential therapeutic option in some patients with COVID-19.

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