A central role for the vascular endothelium in COVID‑19 pathogenesis

Licht, Christoph | $583,472

Ontario Hospital for Sick Children 2020 CIHR Operating Grant

COVID‑19 is a respiratory disease that can lead to a severe lung infection and death in seniors and patients with additional illnesses. Recent studies have recognized severe cardiovascular injury mainly in children and young adults even in the absence of the typical lung disease. Importantly, there are currently no validated vaccines or treatments for COVID-19. Serious and life-threatening cases of COVID‑19 involve uncontrolled immune responses. One important part of the immune system’s first line of defense is the complement system, which typically helps to clear invaders and damaged cells. Recent studies implicated complement as important in COVID-19, as it is known to activate the inner lining of blood vessels, the vascular endothelium. Endothelial activation leads to the attraction of inflammatory cells, which adds to an « inflammatory storm » and increases the risk of blood clotting, together closing a vicious cycle of blood vessel destruction and poor outcome. In a health care system crisis like the current COVID‑19 pandemic, identification of patients in highest need for treatment and early determination of likely patient outcomes are urgently needed. We aim to address these needs by (i) investigating the mechanisms, by which complement injures and activates the endothelium, and (ii) identifying the resulting biological markers (biomarkers) reflecting inflammation and endothelial injury, and correlating them with the outcome of COVID‑19 patients, thus establishing a COVID‑19 risk score. Our study will help to fight the current COVID‑19 pandemic in two ways: (i) identifying complement as important mechanism of inflammation and blood vessel injury will allow for trialing available complement blockers in COVID‑19 patients; (ii) identifying biomarkers predicting patient outcomes will help determining patients in biggest need for help, and – in a desperate shortage of resources – identifying the ones who might have a chance to survive.

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