Even in Mild Cases, Covid-19 Could Damage the Heart

Early on in the pandemic, it became clear that a large percentage of the deaths caused by Covid-19 were related to cardiovascular problems. In March, a study revealed that more than 25% of people hospitalized for the novel coronavirus had signs of heart damage, and nearly a third of those people had no underlying cardiovascular disease. A more recent evaluation of autopsies performed on people who died from Covid-19 found inflammation and injury to the heart in 86% of cases.

Perhaps even more alarming, evidence of heart damage has not only been reported in serious cases of Covid-19, but also in mild or asymptomatic ones. One study looking at college athletes who’d tested positive for the virus but had mild or even no symptoms found signs of inflammation in cardiac MRI scans in 15% of the athletes. And researchers from Germany found that 78% of people who’d recovered from Covid-19 showed similar abnormalities on MRI scans of their hearts taken two months later.

These findings have caused some experts to raise the question of whether Covid-19 should be categorized as a disease of the heart as well as a respiratory infection, and if everyone who tests positive for the virus should be screened for cardiovascular complications. But other scientists and clinicians have pushed back, saying that panic over the virus’s effect on the heart, especially in mild cases, is premature.

An abnormal MRI could mean myocarditis — or it could not

At the root of the debate is whether or not the abnormal cardiac MRIs in people with mild or asymptomatic Covid-19 are evidence of cardiovascular damage that could cause serious complications, like heart failure or arrhythmias. One interpretation of the abnormalities seen in the scans is that they are evidence of myocarditis — inflammation of the heart cells caused by the body’s immune response to a viral infection. In many cases, myocarditis resolves on its own without any lingering issues, but in approximately 1% of people, it can cause sudden death, typically prompted by vigorous exercise. Clinicians have virtually no way of telling which way a case will go.

“Based on what we know from other viruses, myocarditis could potentially be deadly. It is one of the most significant causes of sudden cardiac death in athletes,” says Saurabh Rajpal, MD, a cardiologist at Ohio State University who published the study on cardiac abnormalities in college athletes. “I want to be clear that we’re not saying that Covid can do that, but we have that knowledge from other viral myocarditis […] Most of these cases recover, but a small minority could progress into more severe conditions.”

Not everyone is convinced that the scans depict myocarditis, though. The MRIs show changes that are often seen with the inflammatory condition, but not exclusively. They can indicate other forms of heart damage as well, such as genetic cardiac disorders or inflammatory illnesses like lupus or sarcoidosis. The only way to diagnose myocarditis for certain is with a biopsy of heart tissue, which neither of the studies on mild Covid-19 cases did.

“All of my pathology friends would say that [the studies] do not fit a pathologic definition [of myocarditis] because there is no pathology. I think that’s one simple answer,” says Leslie Cooper, MD, chair of the Department of Cardiovascular Medicine at the Mayo Clinic in Florida and founder of the Myocarditis Foundation. “The more complicated answer, which is, I think, more accurate, is to say that amongst the disorders that cause these imaging features in the heart, myocarditis [is one].”

The real question, Cooper says, is whether the abnormal scans, whatever their cause, lead to serious clinical problems. “Do you have an increased risk of sudden death? If you play sports, will your heart stop? Or will you get cardiomyopathy and heart failure? And that is the critical question that we do not have an answer to.”

The issue of what doctors see on the scans versus what that actually means for patients is so contentious that in September, 51 cardiologists and radiologists signed an open letter asking medical professional societies to recommend against cardiac MRI scans for people who tested positive for the novel coronavirus but were asymptomatic.

Many physicians worry that people — and organizations — will make or recommend major life changes based on these scans without knowing whether or not the results are clinically meaningful. For example, the German cardiac MRI paper is cited as having influenced the Big 10 and the Pac 12 conferences’ decisions to not participate in NCAA football this year — a decision both conferences have recently walked back.

A few organizations tentatively agreed with the letter. In a statement to the medical trade publication MedScape Today, a representative from the American Heart Association said, “The American Heart Association’s position on this is that in general we agree that routine cardiac MRI should not be conducted unless in the course of a study.” The American College of Cardiology, on the other hand, declined to take a stand.

Adding to the confusion is a debate over how novel, and therefore how notable, the abnormal scans really are. It’s well known that severe infections from several viruses, including influenza, respiratory syncytial virus, and coxsackievirus, can cause myocarditis and other forms of cardiovascular injury. Higher rates of heart attacks often overlap with particularly bad flu seasons. But no one has looked at whether signs of cardiovascular damage emerge after mild infections with these viruses.

“We don’t do MRIs in other illnesses. Say, if you had a bad influenza, for example, we don’t routinely do MRI in that setting, so we don’t know if you would see this same feature in other similar disorders or in people who were asymptomatic,” Cooper says.

It’s possible that a typical case of the flu or even a common cold caused by one of the other coronaviruses could temporarily affect the heart without causing any long-term damage. However, there’s no research on the matter, simply because scientists and doctors haven’t had a reason to look without any symptoms to indicate that there’s a problem with the heart.

Myocarditis isn’t the only cardiovascular concern

This isn’t to say that SARS-CoV-2’s potential effect on the heart isn’t serious — it absolutely can be. In a recent article in the journal Science, Eric Topol, MD, a cardiologist and director of the Scripps Research Translational Institute, wrote about the myriad ways SARS-CoV-2 affects the heart, directly and indirectly. “[SARS-CoV-2] can lead to myocarditis (inflammation of the heart), necrosis [death] of its cells, mimicking of a heart attack, arrhythmias, and acute or protracted heart failure (muscle dysfunction),” he writes.

In addition to the rise in arrhythmias and blood clots in people hospitalized for Covid-19, Topol cites an increase in cardiac arrests and sudden deaths outside of the hospital in regions hard hit by the novel coronavirus. There are reports of Covid-19 patients as young as 16 presenting with signs of a heart attack, including abnormal blood tests and electrocardiograms.

“Not only does [the heart] get infected with the virus, but the virus actually replicates in the cardiac cells and makes new infectious particles that can infect other cells.”

There is also mounting evidence that the virus can directly infect heart cells themselves. During autopsies, scientists found the virus in the heart tissue of 24 out of 39 people who died from Covid-19. Two additional studies have shown that SARS-CoV-2 can readily infect, replicate, and destroy heart cells in a petri dish.

“Not only does [the heart] get infected with the virus, but the virus actually replicates in the cardiac cells and makes new infectious particles that can infect other cells,” says Bruce Conklin, MD, a senior investigator at the Gladstone Institutes who led one of the studies. “The full lifecycle is supported by the cardiac cells, so that’s alarming.”

Conklin’s lab showed that the virus caused a unique form of damage to the heart cells, chopping up the muscle tissue in a very specific way. “Like if you’re cutting carrots and somebody wants to cut them exactly an inch apart for their salad,” he says. “As opposed to dicing it up in a random way, which we see in other diseases like genetic cardiomyopathy and some kinds of chemical cardiomyopathies.” The Gladstone scientists found evidence of similar damage in heart tissue from three people who died of Covid-19-related cardiovascular failure.

The question remains, though, whether these cases are the exception or the norm. Despite preliminary data from the studies in asymptomatic college athletes with mild disease, scientists don’t know if the virus only infects heart cells in the most advanced, lethal forms of the disease, or whether people with mild forms of Covid-19 will experience similar damage. It’s possible that the abnormalities seen on the cardiac MRI scans of people who recovered are evidence of direct infection of the heart, or they could very well be myocarditis. It’s also possible that the scans are benign and won’t lead to any lasting problems.

An easy way for doctors to assess how serious cardiovascular abnormalities might be is to look for a protein called troponin in the blood. Troponin is only produced when heart muscle cells are dying, like during a heart attack or a serious case of myocarditis. Since heart cells can’t regenerate, high troponin levels indicate cardiac cell death and more permanent damage. In the German cardiac MRI paper, troponin levels were detectable in 71% of people, but significantly elevated in only 5%. None of the athletes in the Ohio State cardiac MRI study had elevated troponin levels, which suggests there is no permanent damage to the heart.

“It could very well be that some of those people whose pulmonary system is fine are having a severe heart issue which needs medical attention.”

Another issue up for debate is whether some “mild” Covid-19 infections should really be defined as mild. Right now, that evaluation is made based on a pulmonary scale, but that metric might not provide the full picture. “I think you could have severe cardiac effects of Covid-19 with mild pulmonary findings,” says Conklin. “It could very well be that some of those people whose pulmonary system is fine are having a severe heart issue which needs medical attention.”

Cooper, the Mayo Clinic cardiologist, estimates that 15% to 20% of Covid-19 cases, including mild ones on a pulmonary scale, will involve the heart at the time of infection, but less than 1% of those will be serious enough to cause any lasting cardiovascular complications. With more than 33.5 million people infected with the novel coronavirus, however, that’s still a lot of people.

So what does this mean if you were diagnosed with Covid-19 or think you might have the disease?

According to the American Medical Society for Sports Medicine, if you have no symptoms or minimal symptoms, avoid exercise for at least two weeks, or until one week after your symptoms have resolved, whichever is longer. After that, assuming you have no cardiac issues like chest pain or shortness of breath, you can start to ease back into exercising slowly. But listen to your body, and be prepared for your capacity to look a little different for a while. Think going for a walk around the block instead of a run (keep in mind that you should quarantine for at least 10 days since symptoms first appeared plus 24 hours without a fever to make sure you’re no longer infectious to others).

If you’ve had a severe case of Covid-19, your recovery is going to take longer — think months instead of weeks — and you need to check with your doctor before attempting any exercise. And if you ever have any signs of cardiovascular symptoms, either while resting or exercising, you need to see your doctor immediately. They’ll likely recommend you get an EKG and a troponin test, and possibly a cardiac MRI. If those are abnormal or your doctor suspects you have myocarditis or another form of heart damage, expect to be sidelined from any exercise for at least three months and possibly longer. You don’t want to do anything that could strain your heart and cause further damage or, worst-case scenario, a heart attack.

“If you have clinical evidence based upon blood tests that show heart damage in a setting of acute SARS-CoV-2, then we would say three to six months away from [exercise],” Cooper says. “[That’s] based upon other studies that show an increased risk of sudden death and viral replication in the heart with exercise. Again, we’re extrapolating from other viruses to this one. We hope that’s right.”

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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