VASCULAR

do with the receptors that the virus binds to when it gets into the cells. For a virus to get into a cell, it has to attach to a surface protein membrane, a protein on the surface of the cells. It turns out that the receptor to which the COVID-19 attaches is a protein called ACE2, angiotensin converting enzyme 2. The function of this ACE2 is to break down angiotensin 2, a vasal constrictor.

If you have a dysfunction of this receptor because it is being occupied by the virus, then you have a tendency to vasoconstrict (narrowing of blood vessels). And it turns out this ACE2 protein is found in large amounts on endothelial cells and vascular smooth muscle cells. Interestingly enough, they found a lot in the lungs as well, which is one of the major organs affected by COVID.

If the virus protein binds to the ACE2, and the ACE2 is found in good amounts on endothelial cells — which is the lining of the blood vessels — some people feel that the way that the vessels get damaged is because the endothelial cells are getting screwed up basically by the virus attaching directly to the ACE2 protein.

Can you talk about what kind of vascular complications seen in COVID patients?

The most common vascular complication that people with COVID-19 get is not arterial. It’s venous. It’s the high incidence of deep vein thrombosis, pulmonary emboli and micro pulmonary emboli.

The second one would be stroke. I’ve read some reports where up to 5 to 6 percent of patients who have a severe COVID infection where they’re hospitalized — so we’re not talking about somebody with a sore throat, staying at home — experience some sort of cerebral vascular thrombotic event.

Now, some might argue that, well, is it really a direct effect of the virus on the blood vessel like we thought? Or is it really the fact that these patients who are severely diseased, they tend to get some cardiac dysfunction, as well as arrhythmias, which arrhythmias can then predispose to stroke? There’s some sort of debate back and forth.

I’ve personally seen a lot of case reports in the vascular literature about young people who are otherwise asymptomatic people, under the age of 50, showing up with strokes. There have been reports from New York City, in particular, that have described some of these events. There was even a paper that actually was mentioning how often they have seen this.

They were saying that, in general, they may see one case every couple months, and now they’ve been seeing one or two cases a week of young people with otherwise no atherosclerotic risk factor who come in with this, and then later on they test them and they found that they are COVID-positive.

The other thing that people have described as well is people who present with acute limb ischemia (a blockage), which is obviously an arterial problem. Just like the stroke is an arterial problem of the vessels in the neck and the cerebral, this is an arterial problem in the leg.

There have been some case reports of people, again, with no obvious risk factors, who actually were hospitalized with COVID, and they presented with limb ischemia. The interesting thing (is that this is) despite being on prophylactic doses of heparin (a blood thinner). People who are sick, they usually put them on something to thin the blood prophylactically, very low dose, to prevent clots from happening. So these people develop these despite the fact that they were being treated with heparin prophylaxis.

So they’re still developing these blood clots even when they’re on medications to prevent them?

We’re not talking full-dose medications. We’re talking prophylactic pills. It’s not like you’re completely thinning out their blood. You’re giving them the usual prophylaxis that you would give to anybody who’s hospitalized, who’s not ambulating very much, because anybody who’s sick, doesn’t walk, is at risk of developing clots.

Can you talk about how we’re seeing some of these severe complications in people who are young but may have some underlying conditions, such as high blood pressure or obesity?

Any kind of comorbidity is going to increase your risk of complications from any problem that you might develop.

Hypertension, as you know, is something that’s going to damage you over the long term. It’s not going to damage you over the short term. It’s something that takes years before you see the side effects.

Nobody’s found a good explanation, or at least provided an explanation that I could find, as to why these people seem to be more predisposed to having complications from the disease, other than possibly what I was saying about the ACE2.

There’s been papers saying that people who are on ACE inhibitors are protected. There’s been other papers saying people who are on ACE inhibitors are not protected, ACE inhibitors being a blood pressure medication. So we really don’t know, and the current recommendation, the best I can tell, is if you’re on it, don’t stop that medication. If you’re not on it, don’t start it just because of the COVID virus.

Is it unusual to see this type of vascular component with what we initially thought was primarily a respiratory illness? We’ve learned that COVID can cause problems throughout the body.

It’s a little more than we expected, but it’s not totally unusual, because we see these sorts of complications in people who are critically ill from other problems.

The reason people are concerned is the impression — again, it’s an impression — that maybe it’s happening more often than we would have expected. But is it totally unexpected to see these problems? I would say no.

We know that many of these patients who become severely ill have long roads to recovery, and they may still be on blood thinners when they are discharged from the hospital. Is it clear yet how long they may need to be on those?

We don’t (know). The only paper I could find on the subject is a paper that was published by the Italian Coagulation

Hematology Society. These guys in Italy, based on their experience, are saying that prophylactic doses of the anticoagulants heparin or Lovenox or something along those lines should be continued for 14 days after the patient has been discharged home. They are readily admitting that there have been no large trials on that, and their experience is saying, if you send them home after they’ve been critically ill and you don’t anticoagulate them, they’re seeing some people bounce back with problems in terms of clotting.

You’re not talking about sending them on a full dose. In anticoagulants, there’s prophylactic doses and there’s therapeutic doses. So prophylactic doses are for people who don’t have the problem and you’re trying to obviously prevent them from getting the problem.

And then there’s the therapeutic, which is, OK, the guy was in the hospital, had a pulmonary embolism, and now he’s being sent home on a therapeutic dose. Obviously the one who had those things, they need to go home on a therapeutic dose. Those are the ones who have a risk of bleeding complications. But if you sent somebody out on a prophylactic dose, the risk of bleeding is very, very, very small.

Can you talk about why some of these patients are ending up on dialysis, in kidney failure?

Any time you’re basically sick to the point of requiring a ventilator, you have one organ failure. When you have one organ failure, you’re obviously not perfusing well. The systemic inflammatory response that is affecting your lungs is also affecting your system in general, and you get what is called acute kidney injury. Anybody who’s critically ill on a ventilator is at significant risk of developing it.

It’s not necessarily a direct effect of the virus, although we go back to this ACE2 protein. It is found in a significant amount in the renal tubules. But still, despite that, the majority of the mechanism is because of being critically ill, and acute kidney injury happens with being critically ill. I don’t think it’s unique to the COVID situation.