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COVID Creates Inflammatory Response In Tissues: Prof Faisel Khan

In an insightful chat with BW Healthcareworld, Prof Faisel Khan, Deputy Head of Systems Medicine Division, Professor of Cardiovascular Sciences, University of Dundee, speaks about the health complications associated with COVID-19 and more. Excerpts:

COVID is a respiratory disease, then why and how is it on a spree of attacking different organs along with multiple syndromes?

COVID-19 is thought of as a respiratory disease, but we know now that cardiovascular complications are one of the major associated threats, partly due to the way the virus gets into the body.

The reason it affects these multi organ systems is because SARS-COV-2 has a spike protein which will attach to an enzyme, called ACE2, as a vehicle to get into all our cells. 

Most major diseases are related to inflammation and this virus creates a huge inflammatory response in our tissues. When you get inflammation, you activate processes which will cause damage to lots of organs. Respiratory, kidney, brain and cardiovascular diseases are hugely affected by inflammation. 

ACE2 is very highly expressed on the lining of all blood vessels, the endothelium. The entry into the endothelium is a prominent feature of this virus and part of the reason why it causes so much blood vessel damage. Our research is looking at the consequences on the blood vessels of people who've had this virus.

How is damaging blood vessels different from a blood clot caused by COVID?

One of the main factors that determines clot formation is the function of the endothelium. These cells are your first line of defence against pathogens in the blood and this lining controls lots of important factors related to cardiovascular disease, such as the diameter of the blood vessel. Healthy blood vessel have larger diameters to allow more blood flow but the lining also controls clotting as well as inflammation and metabolism.

The more blood vessel are damaged, the more likely you are to form a clot. COVID essentially is not doing anything different from the normal processes that cause clots. It's merely accelerating them because of the huge inflammation it creates.

What is the probable cause of heart attack among the patients who recover from COVID?

COVID isn’t necessarily causing cardiac disease in a new way, but the inflammatory response makes heart attacks more likely by increasing existing risk factors. It can cause lots of different abnormalities within the cardiovascular system and lead to myocarditis, arrhythmias and – as we have already discussed – clotting.

Not everybody who has COVID is going to have a heart attack or, more broadly, experience heart disease, but the inflammatory mechanisms that are activated by COVID increases the likelihood of these events.

Does COVID causing damage to blood vessels also create coronary arteries blockage? If yes, then how is it different from the usual blockages?

Once again, inflammation is the key factor here. It isn’t a different type of blockage. COVID can cause clots in the coronary arteries because of the damage to the lining amplified by inflammation which affects the clotting system. It is mainly the same underlying process as if you were overweight or had diabetes, high cholesterol or any other factor that increases your cardiovascular disease risk.

It is like the way that seasonal flu leads to an increase of heart attack during that winter period. Flu cause a similar systemic inflammatory response that activates all these issues which predispose people to more heart related problems. That is why people who have existing cardiovascular disease are high list for getting vaccinated against both seasonal flu and COVID.

What made you believe that neutrophil could be a possible link to COVID causing blood vessels damage?

We know that from existing research that neutrophils play a very important role in the immune system fighting infection. In a condition like diabetes, which has a large cardiovascular component, the way the neutrophil interacts with the lining of the blood vessel is a key player in causing damage to the blood vessel.

If you have a high number of neutrophils in your body because of COVID, then you have a poorer overall outcome. When patients get COVID, they are more likely to experience some other complications related to the cardiovascular system, but the mechanisms underlying that haven't been deciphered. That is part of what we are trying to discover.

When neutrophils are activated, by COVID or by another mechanism, these cells in the blood will pass through the endothelium and lodge themselves inside the blood vessel wall. When there, they activate lots of other harmful processes like oxidative stress and release other proteins called neutrophil extracellular traps or NETS. From other studies, such as in diabetes, these are known to be related to poor cardiovascular outcome. We think that the interaction between NETS and the endothelium is a key factor to damaging that blood vessel wall and then promoting all the other problems like the clotting, like the narrowing of the blood vessel. From there, it also contributes further to inflammation and becomes something of a vicious cycle.

At present is there any solution available to prevent such damage?

There is no specific treatment for managing the problems associated with the cardiovascular system. Doctors try and keep the inflammation under control and that's why treatment and studies to date have focused on various drugs and intravenous steroids.

These treatments target the inflammatory process rather than directly targeting the heart directly, but by reducing inflammation they also help to reduce cardiovascular consequences.

Ensuring that blood pressure, cholesterol and other cardiovascular risk factors are optimally managed is also important.

Have you been able to identify any specific age group that has high risk of coming under its grip?

We are still carrying out our studies and so have not analysed any data according to age. Generally, however, the older you are, the more existing cardiovascular risk factors you're likely to have and the worse the consequences of COVID infection are likely to be in cardiovascular terms. That’s why people who naturally have more comorbidities related to age have been targeted for vaccination first to ensure they are protected. 

That said, younger people with risk factors like high blood pressure and diabetes are also more likely to be more adversely affected by COVID than the general population.



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