News & Views: Myocarditis and COVID-19

This article was updated on April 26, 2023.

Myocarditis, or inflammation of the heart, has become a topic of conversation related to COVID-19. As such, we wanted to review the basics of myocarditis as well as take a closer look at what is known about myocarditis following COVID-19 infection or vaccination.

Myocarditis: The basics

The heart wall is composed of three layers: epicardium, myocardium and endocardium. The myocardium is the thickest of these and is the layer responsible for the pumping of the heart. Myocarditis occurs when the myocardium becomes inflamed and can result in abnormal heart rhythms, called arrhythmias. Because of altered beating, other parts of the body may not get enough blood. In severe cases, blood clots can form in the heart causing strokes or heart attacks.

Symptoms

Some people do not experience symptoms; however, common symptoms typically include chest pain, abnormal heartbeat, shortness of breath, fatigue and accumulation of fluid, particularly in the legs, ankles or feet. Children experiencing myocarditis might also experience fainting, difficulties breathing or rapid breathing.

Because myocarditis is often caused by an infection, individuals may also have symptoms related to such, including diarrhea, headache, muscle or joint pain, fever or sore throat.

Causes

Myocarditis can result from a variety of situations, including both infectious and non-infectious mechanisms.

The following pathogens are known causes of myocarditis:

• Viruses, including adenovirus, influenza, hepatitis B, hepatitis C, parvovirus, herpes simplex virus, echoviruses, coxsackievirus, Epstein-Barr virus (EBV), rubella, human immunodeficiency virus and coronaviruses, including SARS-CoV-2
• Bacteria, including staphylococcus, streptococcus, Corynebacterium diphtheriae and Borrelia burgdorferi, the bacteria the causes Lyme disease
• Parasites, including Trypanosoma cruzi and Toxoplasma gondii
• Fungi, including those from the Candida, Aspergillus and Cryptococcus genera

Myocarditis that occurs from infectious causes can be the result of direct action of the pathogen on the heart muscle or indirect mechanisms, such as immune activation.

Non-infectious causes of myocarditis can include medications, including some illegal substances; chemical exposure; radiation or medical conditions, like lupus, Wegener’s granulomatosis, sarcoidosis or some types of arteritis.

Check out this extensive list from the American Heart Association.

Diagnosis

Myocarditis can be diagnosed by blood tests (e.g., serum troponin levels), chest X-rays, electrocardiograms, echocardiograms, MRI, or in some cases by more invasive procedures, such as cardiac catheterization or biopsy.

Treatment

Myocarditis typically resolves on its own in a few weeks, but it could take several months. In some cases, the cause (e.g., an infection) or symptoms may be treated with medications or by mechanical means, like pacemakers, implantable cardioverter defibrillators (ICD), intra-aortic balloon pumps or extracorporeal membrane oxygenation machines (ECMO). In rare cases the damage to the heart may be so severe that the patient requires a heart transplant.

Myocarditis & COVID-19 infection

Myocarditis has been identified following infection with other coronaviruses, including SARS and MERS, but SARS-CoV-2, the cause of COVID-19, appears to have a more significant impact. For example, according to the CDC, myocarditis among inpatients increased by more than 40% during the first year of the COVID-19 pandemic (2020) compared with the previous year (2019). Further, patients hospitalized with a COVID-19 diagnosis were almost 16 times more likely to experience myocarditis than for those hospitalized for other (non-COVID-19-related) reasons. Risk appears to increase with age, and hypertension has been the most common pre-existing condition but is not a pre-requisite. Males are more often affected.

While myocarditis has been associated with COVID-19 infection, the mechanism that causes it remains unclear. SARS-CoV-2 has been found in the heart muscle of some, but not all, patients following biopsy or autopsy. Inflammation caused by “cytokine storm” may also play a role, whether alone or in combination with viral infiltration. Other theories, albeit less often suggested, include effects caused by overall metabolic changes or damage to endothelial cells.

Increased troponin levels, coupled with imaging when possible, have been useful for diagnosing myocarditis during COVID-19 infection; however, myocarditis occurs in only a small number of COVID-19-positive cases. Although exact rates have been variable among studies, it is estimated that myocarditis occurs in less than 1% of hospitalized COVID-19-positive patients. The variability among studies may be due to several factors. First, since many reports are case studies, sampling errors can complicate the establishment of rates. Second, diagnosis-related issues often complicate clinical identification. Specifically, among hospitalized COVID-19 patients, diagnosis has been complicated by issues, such as difficulty transporting critically ill patients, attempts to limit exposure of others to stable COVID-19-positive patients (i.e., limited transport to other departments, like radiology), and testing limitations, including inability to get quality images on patients receiving intensive care. For mild infections, patients may not seek care or may be asymptomatic, leading to underdiagnosis.

Symptoms of myocarditis during COVID-19 infection are similar to those of myocarditis from other causes, particularly fatigue, chest pain and irregular heartbeat.

Most patients diagnosed with myocarditis recover; however, it has been observed that high levels of troponin are also indicative of more severe disease and, therefore, at least in some cases, higher mortality.

While some studies have attempted to evaluate rates of myocarditis in COVID-19-infected athletes being tested for return-to-play protocols, the studies have not provided proof of utility. Most specifically, rates of positive findings have been low and have not always correlated with symptoms. As such, widespread testing has not been enthusiastically embraced or recommended.

Myocarditis & COVID-19 vaccination

Myocarditis has been associated with receipt of COVID-19 vaccines. This effect has most often followed receipt of mRNA versions, but it has also occurred following receipt of the protein- and adenovirus-based versions (Novavax and J&J/Janssen, respectively). While studies have published variable rates, this severe side effect is currently estimated to occur in about 1 to 10 of every 100,000 people vaccinated with a COVID-19 mRNA vaccine. However, these rates are higher if populations are subdivided, with the greatest risk being for males younger than 40 years of age following the second dose, albeit people have also experienced this side effect after first doses and booster doses as well. The variability among studies can be attributed to different experimental approaches and the likelihood of underreporting by some populations, either due to lack of symptoms or severity of presentation.

The most common symptom is chest pain, which typically occurs within 4 days of the second dose but can occur after any dose and sooner or later than 4 days following vaccination. In some cases, patients also experience fever or muscle pain. Most patients do not have underlying conditions.

Typically, individuals have elevated troponin levels, and many have abnormal heart imaging if checked. Although many affected individuals require hospitalization, most are considered mild and hospital stays are short (e.g., less than 3 days). Recovery occurs relatively quickly without the need for ongoing medical intervention in most patients.

Mechanisms leading to this side effect remain unclear but are most commonly thought to result from hyperactivation of the immune response.

Because of the risk associated with infection, including that of myocarditis, individuals are recommended to get vaccinated despite this side effect. However, the FDA has added a warning to the mRNA vaccines, and the CDC recommends that any suspected case be submitted to the Vaccine Adverse Events Reporting System (VAERS).

Although the literature is limited, individuals affected by myocarditis after the first dose who subsequently received the second dose tolerated it well. However, due to a lack of data, the CDC’s current recommendation is that “subsequent doses should generally be avoided” for people who develop myocarditis or pericarditis after a dose of an mRNA COVID-19 vaccine. (See “Considerations for COVID-19 vaccination.") If an individual opts for an additional dose because of personal circumstances, the CDC advises waiting until after resolution of symptoms and determination of complete recovery per appropriate clinical testing as well as increasing the time between doses to eight weeks.

Myocarditis & COVID-19: Key takeaways

Myocarditis is rare, but can occur after a variety of infections, including COVID-19. It has also been associated with receipt of COVID-19 vaccines. COVID-19 infection leads to myocarditis more frequently than other viral agents, including other coronaviruses. Likewise, infection is at least seven times more likely to cause myocarditis than vaccination.

Although myocarditis following infection occurs more often in older males, that which follows vaccination is more frequent in young adult males (12 to 39 years of age). Likewise, vaccinated individuals who experience myocarditis most often have mild cases that resolve in a short timeframe without the need for ongoing interventions.

Patients exhibiting signs of myocarditis should be evaluated for COVID-19 infection or recent vaccination. Any cases identified following vaccination should be reported to VAERS.

Resources

Clinical Considerations: Myocarditis and Pericarditis after Receipt of mRNA COVID-19 Vaccines Among Adolescents and Young Adults, CDC

Diagnosis and Management of Myocarditis in Children: A Scientific Statement From the American Heart Association, AHA