Our Narrow Understanding of Myocarditis After COVID Vaccines

As the wave of vaccination to protect against COVID-19 spreads across the world, surveillance for possible vaccine-related adverse events remains active.

So far, no data have emerged to definitively link the mRNA vaccines manufactured by Pfizer/BioNTech and Moderna with serious adverse events other than rare episodes of anaphylaxis, and the vaccines are performing well in their intended goal of reducing COVID-19 morbidity and mortality in vaccinated populations. Overall, the vaccines have been an unparalleled scientific success — a source of light in the relentless storm of the COVID-19 pandemic.

Currently, there is a focus on the possible link between the mRNA vaccines and myocarditis. This attention has grown out of a small number of reported potential cases, predominantly in the U.S., Europe, and Israel. In both children and adults, cases of myocarditis have been identified shortly after administration of these vaccines — typically 2 to 4 days after receiving the second dose — and appear to follow a relatively benign course.

Thanks to the detailed reports published in the literature, there is now an initial collection of data on these patients and their relevant clinical and diagnostic findings. Patients have typically had symptoms of chest pain, and were subsequently found to have elevated levels of troponin, abnormal electrocardiograms, and cardiac MRI patterns consistent with myocarditis.

Thankfully, feared serious complications of myocarditis such as circulatory failure or dangerous arrhythmias appear to be exceptionally uncommon. Ideally, these reports will serve as foundational knowledge as our study of these relationships continues.

However, this research is still in its infancy and there remain several challenges in understanding the potential relationship between these vaccines and myocarditis.

Gaps in Our Knowledge

First, myocarditis remains a heterogenous disease with highly variable presentations and causes. As such, it is challenging to establish a comparison between historical cases of myocarditis and those seen in the current case reports.

Second, the retrospective nature of the current case reports leaves them open to bias and limits the ability to offer an appropriate matched control group. The widespread press coverage of the topic could certainly result in availability bias on behalf of providers, and the lack of a protocolized diagnostic approach to these cases leaves open the possibility of missed alternative diagnoses (particularly infection with non-SARS-CoV-2 viruses, which have been previously implicated in myocarditis).

Third, even if a causal relationship is established between COVID-19 vaccinations and myocarditis, the quantification and communication of risk is a complex task.

Again, the question remains, As compared to what? Should we compare the risk of myocarditis associated with vaccination to the rate of myocarditis in those affected with COVID-19? To the risk of myocarditis in age-matched controls? To the risk of myocarditis in those receiving other vaccines?

Moving Toward a Better Understanding

As always, history holds valuable lessons: Other vaccinations have been previously linked to myocarditis. For example, surveillance and prospective data in patients receiving smallpox vaccination have identified higher than expected rates of myocarditis.

These studies offer useful insights into our review of the current literature on COVID-19 vaccine recipients. Many cases of myocarditis after smallpox vaccines would have never been uncovered without a prospective trial, as many patients would not have sought medical care for the mild symptoms they experienced.

Many vaccine recipients were likely to attribute symptoms of chest discomfort to the typical myalgias expected to occur after vaccination, and many of the symptoms may have responded to over the counter anti-inflammatories. As such, retrospective surveillance studies likely underreport the incidence of myocarditis after smallpox vaccination.

Though the same may be true of COVID-19 vaccine recipients, we cannot draw these conclusions without prospective data. Therefore, the studies on smallpox vaccination and myocarditis should serve as an important guide for future investigations into the relationship between COVID-19 vaccination and myocarditis.

The growing number of reported cases of myocarditis after COVID-19 vaccination are an important contribution to the scientific literature. However, these should be seen as preliminary, and should serve to foster robust clinical, epidemiologic, molecular, and behavioral investigations in the future.

Medical providers should be aware of the potential link between myocarditis and COVID-19 vaccination, but must continue to use best clinical judgement in evaluating patients and discussing risk. The COVID-19 vaccinations are a critical component in the global battle against a devastating pandemic, and the individual and public health benefit of these vaccines remains robust.

Those who are eligible to receive the COVID-19 vaccines should continue to do so.