COVID-19 Research Grant
Prof Faisel Khan, University of Dundee
Summary: Inflammation in the body caused by COVID-19 might be responsible for harmful effects on the blood vessels, and blood cells, called neutrophils, might be the link. This project will study whether increased activation of neutrophils contributes to development of long-term disease of the blood vessels in COVID-19 patients and whether reducing their activation with drug treatment has beneficial effects. Targeting neutrophils in this way could be a treatment option for reducing blood vessel and heart complications in patients with COVID-19.
COVID-19, which is caused by the virus SARS-CoV-2, is having a devastating impact on health worldwide. The major cause of death in patients who have COVID-19 results from development of complications in the lungs. However, the harmful effect of COVID-19 is excessively high in people who have pre-existing diseases of the heart and blood vessels. Also, COVID-19 can cause ‘new’ damage to the heart and blood vessels in people who have no pre-existing disease. The lining of blood vessels, called endothelium, acts as a barrier and first point of contact for the virus that causes COVID-19. From recent research studies, there is evidence that the virus causes damage to the endothelium which in turn leads to disease of the heart and blood vessels, particularly the very small blood vessels, called microvessels.
It is thought that inflammation in the body caused by COVID-19 might be responsible for some of the harmful effects on the blood vessels. Inflammation is a protective mechanism activated by the body’s immune system to fight infection, remove harmful toxins and help in the healing process. However, inflammation can also have detrimental effects on the human body, especially when it does not resolve and becomes persistent, as in COVID-19.
Professor Khan and his team believe that abnormal activation of a type of white blood cell, called the neutrophil, that is important in the body’s immune response, might be the link between COVID-19 and damage to the blood vessels. Importantly, Professor James Chalmers and colleagues have recently shown that a new drug, called brensocatib, reduces the abnormal activation of neutrophils and improve the symptoms of patients who have bronchiectasis, a lung disease that is caused by inflammation.
The aims of the project are to explore whether: –
- abnormally high activation of neutrophils, caused by inflammation, is responsible for long term damage to the endothelium and small blood vessels in COVID-19 patients.
- reducing activation of neutrophils with the drug brensocatib reduces damage to the endothelium and improves the function of the blood vessels.
The team will assess the function of the small blood vessels over 12 months in 120 patients who have had COVID-19 to see if this is abnormal compared with healthy people who have not had COVID-19. They will apply small amounts of chemicals to the skin and use a laser machine, which measures blood flow in the microvessels, to assess how well the blood vessels are working. They will also take blood samples to measure the activation of neutrophils and see if high levels of activation are linked to blood vessel damage.
Also, they will use these methods in 100 patients who have been hospitalised with COVID-19, to compare the effects of the drug brensocatib against a dummy drug (placebo) on the activation of neutrophils and function of the blood vessels. These measurements will be carried out before and after 28 days of treatment.
The study will show whether increased activation of neutrophils contributes to development of long-term disease of the blood vessels in COVID-19 patients and whether reducing their activation with drug treatment has beneficial effects. Targeting neutrophils in this way could be an important treatment option for reducing blood vessel and heart complications in people who have COVID-19.