I have long been frustrated that people tend to lump the effects of COVID into two buckets – (1) infections in young persons that tend to be asymptomatic or mild and (2) infections in the elderly that may land them in the hospital or even result in death. Both extremes certainly exist and are common outcomes, but there is so much more in the middle. There are children and young adults who die and there are young adults who develop very severe illness and may suffer disabling complications including heart attacks, strokes and residual lung disease, deconditioning and PTSD following prolonged mechanical ventilation. Further, there is another set of people with an average age in their late thirties or early forties that develop long-term, disabling effects long after they appear to have recovered from their COVID infection called “long-haulers,” who I have previously written about. We need to change he discussion of COVID from one of full recovery or death to one of a spectrum of disease outcomes, including many outcomes that we simply do not understand yet, nor have we had sufficient time to know the long-term effects. One complication of COVID on this spectrum is myocarditis.
The subject of today’s article is myocarditis, a complication of COVID that has been recognized since April, but has recently attained attention due, in part, to the occurrence of this condition in college and pro athletes and some attention-getting decisions about whether college teams would play football this season, in no small part due to concerns about myocarditis.
What is myocarditis?
Myocarditis is inflammation of heart muscle – the myocardium. It may be caused by many different things, but viral infections are among the most common. Among the most common viruses to cause myocarditis are adenoviruses (a group of viruses that cause cold-like illness, pneumonia, diarrhea and pink eye in people of all ages), coxsackievirus (the cause of hand, foot and mouth disease in children) and other enteroviruses (viruses that enter the body through the intestine and generally cause cold symptoms).
How does myocarditis present?
The classic presentation of viral myocarditis is a report of a viral-like illness with fever, muscle aches and upper respiratory symptoms followed by the onset shortness of breath, chest pain and/or palpitations, and fast and/or irregular heart-beats. Not everyone recounts a preceding viral-like illness, but in those that do, the symptoms of heart failure may present over a few days to a few weeks after the viral illness.
When these patients are evaluated, they may have abnormal electrocardiograms, an echocardiogram may be normal or may show a reduction in the heart’s pumping effectiveness, or a cardiac MRI may show areas of swelling or inflammation in the wall of the heart, or even scarring. In addition, a blood test for troponin, a protein in heart muscle, may be elevated indicating that the heart muscle cells have been damaged.
How does a viral illness cause myocarditis?
We haven’t been sure whether the virus actually attacks or invades the heart muscle cells or whether the inflammation associated with the virus or the immune response to the virus is what harms the heart muscle, or possibly both mechanisms could be at play. A recent study (Lindner et al, JAMA Cardiology, July 27) in patients with myocarditis from COVID who died showed that the causative virus, SARS-CoV-2 could be detected attacking and invading heart muscle cells.
What happens to patients with viral myocarditis?
We don’t yet know for patients with myocarditis from COVID. Before COVID, patients with viral myocarditis often recover on their own or with anti-inflammatory medications in a matter of months. Most will recover their full heart function. However, some patients can experience life-threatening arrhythmias and some patients go on to develop serious heart failure. A weakness in pumping of both sides of the heart is one of the main predictors of death in patients with severe myocarditis.
So, what do we know about myocarditis in COVID patients?
The first case of COVID-19 infection in a patient that resulted in fulminant myocarditis as a complication was reported on April 10 in a 63-year-old man with no history of heart disease or underlying hypertension. This patient had elevated levels of the heart muscle protein, troponin, in his blood, enlargement of part of his heart, low pumping movement of his heart muscle and the pumping effectiveness of his heart was reduced by 40 – 50 percent (LVEF 32%). In this particular case, the patient’s heart function largely recovered, however he died of secondary infection on the 33rd day of hospitalization.
Since then, we have seen heart muscle involvement in many cases of patients sick enough to have required hospitalization. But, myocarditis is not the only manifestation of heart disease from COVID. COVID actually produces a pro-thrombotic state, i.e., a greatly increased tendency of the blood to clot abnormally. This has resulted in some patients experiencing significant pulmonary embolism (blood clots to the lungs), which if severe can impair the functioning of the right side of the heart; myocardial infarction, i.e., heart attacks due to blood clotting in the arteries that provide the blood supply to the heart muscle; and clotting of stents in coronary arteries producing heart attacks in those who previously had angina, underwent a cardiac catheterization and were found to have a blockage in their coronary artery for which a metal strut of a sort is placed in the artery to open up the blood flow through that artery. In addition, some patients with COVID develop a shock-like state, and we know that the imbalance between the oxygen and metabolic requirements during shock and the lower supply can cause abnormalities in the heart muscle and a release of troponin into the blood, thereby making this condition difficult, if not impossible, to distinguish from myocarditis.
More recently, patients who recovered from COVID have been evaluated with cardiac MRI looking for signs of myocardial involvement. It should be noted that we have not generally screened asymptomatic patients recovering from other viruses to look for evidence of myocarditis, so we don’t know if asymptomatic myocarditis is a common occurrence with other viruses.
These recent studies showed that a significant percentage of persons who recovered from COVID, including those who experienced relatively mild illness were found to have cardiac MRI evidence of myocarditis, including athletes.
The long-term impact of COVID-19 myocarditis, including the majority of mild cases, remains unknown. In symptomatic patients, especially those with significant involvement of their heart and impairment to their heart’s pumping effectiveness, there is a risk of arrhythmia as well as progression to fulminant heart failure and cardiogenic shock. But, for those who are asymptomatic, whose myocarditis is being picked up incidentally on cardiac imaging, we simply do not know yet why they developed this complication, what the risks are, whether some will go on to develop significant cardiac problems, or whether all of these individuals will recover with time.
Perhaps it is not surprising that myocarditis can result from infection by the SARS-CoV-2 virus since its target, the ACE2 receptor protein, can be found in the cell membranes of heart muscle cells. But, a report in July garnered a lot of attention.
In a study in JAMA Cardiology published on July 27, Puntmann et al reported that in a cohort of 100 patients recently recovered from COVID-19, “cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.”
53% of the patients were male and the mean age was 49 years. The median time interval between COVID-19 diagnosis and the cardiac MRI study was 71 (range 64-92) days. 67% of the patients were considered to have had mild illness and recovered at home, while 33% required hospitalization. At the time of the cardiac MRI study, 76% of the patients had elevated levels of the heart muscle protein, troponin, in their blood signifying heart muscle injury.
As of the time of the cardiac MRI study, 17% of patients reported atypical chest pain, 20% reported palpitations, 36% reported ongoing shortness of breath and general exhaustion, of whom 25 noted symptoms during less-than-ordinary daily activities, such as a household chore. The authors conclude their paper by stating, “although the long-term health effects of these findings cannot yet be determined, several of the abnormalities described have been previously related to worse outcome in inflammatory cardiomyopathies.”
Also recently, cases of post-COVID myocarditis have been reported in college and professional athletes. We are awaiting a medical publication that is rumored to show that approximately 15 percent of Big Ten football players who were infected with COVID demonstrated evidence of myocarditis in follow-up evaluations. However, until this paper is peer-reviewed and published, we don’t have any of the details we need to draw conclusions from this.
From everything we know thus far, the clinical presentation of SARS-CoV-2 myocarditis varies among cases. Some patients may present with no symptoms and the myocarditis is detected only because of a screening protocol for athletes, some may present with relatively mild symptoms, such as fatigue and mild shortness of breath, whereas others report chest pain or chest tightness on exertion. Some patients do deteriorate, showing symptoms of tachycardia (fast heart beat) and acute-onset heart failure with cardiogenic shock. In these severe cases, patients may also present with signs of right-sided heart failure. The most emergent presentation is fulminant myocarditis, defined as ventricular dysfunction and heart failure generally within 2–3 weeks of contracting the virus. This complication occurred in a beloved nurse practitioner who was in her 40s and cared for children at St. Luke’s.
While the acute inflammation and injury to the heart are the current focus receiving attention, the long-term effects of healed myocarditis are completely unknown. We have seen in patients with other forms of myocarditis that in the process of healing, scarring of the heart muscle can disrupt the normal electrical pathways of the heart and result in life-threatening arrhythmias, even when the acute inflammation has resolved.
Post-COVID myocarditis in Idaho
I spoke to two experts here in the Treasure Valley to see what they were seeing and what their thoughts about this complication are. I interviewed Dr. Andy Chai, a cardiologist at St. Luke’s Health System who specializes in advanced heart failure and transplant cardiology and who serves as the medical director of St. Luke’s Clinic-Heart Failure and Dr. Nathan Green, an interventional cardiologist with St. Luke’s Health System who serves as the medical director of the Heart and Vascular Service Line at St. Luke’s.
Both doctors indicated that they are seeing cases of myocarditis related to COVID here in Idaho and while these patients have most often ranged in age from their thirties to their fifties, they have also had disease ranging from mild to severe, including patients who have died from their myocarditis.
Both doctors lament how little we know about this condition at this time. They certainly expect that those with myocarditis who have well-preserved heart function, limited areas of involvement of myocardium and low levels of troponin elevation are likely to do well. For others, who have more significant inflammation, we don’t yet know what to expect, but we are managing these cases much like other cases of viral myocarditis and following up with serial evaluations to monitor their progress.
I did ask both doctors about sports this fall and winter given the amount of disease transmission we have in the communities we serve, as well as this yet poorly understood risk of myocarditis in athletes who might become infected. Neither doctor felt that the threat of myocarditis should be the determining factor of whether sports are played. The risk of transmission of COVID among those who participate in sports and to their families, teachers and others is certainly worth consideration of whether middle schools and high schools hold sports events this fall. However, perhaps more important if a school is going to have athletic programs this fall is how strong the operational plans of each school are.
As for an athlete who has seemingly recovered from COVID and now has an abnormal result on a cardiac MRI screening, as to whether that athlete should sit out for the season was a much more difficult decision. One doctor pointed out that we simply do not have good guidelines as to how safe a significant amount of exercise is for someone with myocarditis. Pre-COVID, we were generally only seeing symptomatic patients with viral myocarditis, and we tend to recommend limited exercise such as walking until we see the myocarditis resolve. One doctor suggested that if the athlete’s participation is especially compelling – a professional athlete whose family’s income is at risk, especially when you consider the much more robust safety protocols they have in place and resources available to protect these athletes or a collegiate athlete with aspirations of going pro- it makes it more difficult to tell that athlete they must sit out the season if the myocarditis appears to be subclinical or very mild. However, for student athletes in middle and high school, it seems prudent to exercise more restraint until we know more about this condition.
I then brought up the long-haulers who have significant symptoms and/or disabilities months after supposedly recovering from COVID, some of whom have reported chest pains, palpitations, and/or shortness of breath with relatively mild exertion. I asked whether these individuals need to be evaluated for possible myocarditis and both doctors indicated yes, without any hesitation.
Finally, I asked the doctors a question sure to make any cardiologist cringe. I asked whether in light of the not infrequent occurrence of myocarditis following COVID and the potential for impairment of heart function and certain EKG findings known to place patients at risk, might this be one more reason why people should not take hydroxychloroquine or hydroxychloroquine plus azithromycin for COVID, and both immediately and emphatically agreed that these medications might be even more likely to cause harm in the setting of a COVID patient who has developed myocarditis.
So, I have told you most of what we know at this time about myocarditis in the setting of or following COVID infection. Perhaps it is equally important to tell you what we don’t know.
- We don’t know the prevalence of this complication. In other words, we don’t know what percent of people who are infected with COVID go on to develop myocarditis.
- We don’t know who is at risk for developing myocarditis and what determines who will develop myocarditis and who won’t.
- We don’t yet know the long-term effects of myocarditis. Do most of the people who develop myocarditis recover on their own in a matter of months? Do some have long term heart problems?
- Should we be screening everyone who recovers from COVID for this condition or are there certain individuals who should be screened? If so, when and how often should they be screened?
- For those who have mild myocarditis, is it safe for them to exercise? How much, how often and at what intensity?
- If someone with myocarditis following COVID gets re-infected with COVID, will they develop a recurrence or a worsening of their myocarditis?
No doubt, we will learn more about this condition with time. As we get important new information, I will be sure to share it with you.