Myopericarditis No More Common After COVID-19 Shots Than Other Vaccines

Myopericarditis is no more likely to occur after receiving a COVID-19 vaccine than it is after getting a flu shot, according to a meta-analysis of studies encompassing more than 400 million vaccinations. In fact, the risk of this complication is much lower than that seen with the smallpox vaccine.

The takeaway from this study, as from numerous reports that came before it, is that heart inflammation is extremely rare with COVID-19 vaccines, even after a booster dose. Also affirmed, however, is the observation that some subgroups were at higher risk than others—males, younger individuals, those getting a second dose, and those receiving mRNA vaccines—leading the researchers of the current paper to call for caution.

“Although the results of our analysis place the risks of COVID-19 vaccination into perspective, the decision to vaccinate should be informed by appropriately weighing the benefits and harms of COVID-19 vaccination, the local risk of exposure to COVID-19 infection at the time, and the risk of myopericarditis from COVID-19 infection itself,” they write in the Lancet Respiratory Medicine.

First authors Ryan Ruiyang Ling and Kollengode Ramanathan, MD (National University of Singapore), in an email to TCTMD, said that while myopericarditis is a known, though infrequent, complication after smallpox vaccination, there’s little knowledge about its frequency with other vaccine types.

They pointed out that only five of the 22 publications in their meta-analysis addressed vaccines that were aimed at neither COVID-19 nor smallpox. This might suggest underreporting in earlier eras, Ling and Ramanathan noted. More recently, “there have been advancements in diagnostic methods (eg, MRI, widespread echocardiography, biopsy), which play a larger role in diagnosing myopericarditis.” Moreover, today’s surveillance systems are enabling cardiologists to more readily diagnose and treat the condition.

Kate Hanneman, MD, MPH (Toronto General Hospital/University Health Network, Canada), whose work has documented myocardial inflammation and cardiac abnormalities in COVID-19 patients and those with myocarditis after vaccination, said the meta-analysis offers valuable information.

A strength, she told TCTMD, “is that this is pooled data, of course, from many studies and many, many, many patients, so I think that really [bolsters] the evidence to show us that the overall risk of myopericarditis after receiving a COVID vaccine is low.” This study also adds a layer of context by comparing among the various vaccines, Hanneman noted.

Complication Quite Rare

The investigators identified 22 studies published between 1947 and 2021 that evaluated the risk of myopericarditis after vaccination. Half of these studies looked at COVID-19 vaccines and half at other vaccine types. Overall, the myopericarditis incidence was 33.3 cases per million vaccine doses. It did not differ between COVID and non-COVID vaccines as a whole (18.2 vs 56.0 cases per million doses; P= 0.20). Compared with the COVID-19 shots, risk also was similar with influenza vaccines (1.3 cases; P = 0.43) and other non-smallpox vaccines (57.0 cases; P = 0.58). However, incidence was higher with vaccines aimed specifically at smallpox (132.1 cases; P < 0.0001).

Within the COVID-19 group, myopericarditis was more common for males than for females (23.0 vs 5.1 cases per million doses; P = 0.02), in people under age 30 versus older (40.9 vs 2.9 cases; P < 0.001), and those receiving mRNA vaccines compared with non-mRNA vaccines (22.6 vs 7.9 cases; P = 0.001). Compared with after the first dose (7.2 cases), risk was higher after a second (31.3 cases) but not after a third dose (3.0 cases; P < 0.0001).

Ling and Ramanathan told TCTMD that countries around the world have put various policies in place to address the at-risk subgroups. “For example, in Singapore, it is recommended to avoid strenuous exercise for 2 weeks following vaccination. In other countries national guidelines have highlighted the indication and contraindications for vaccine subtypes,” they said. “In addition, policies such as preferentially offering non-mRNA vaccines to males, particularly those younger than 18 years, could be considered to manage the risk of myopericarditis, while considering the overall benefits and harms of the vaccine.”

Hanneman praised the paper’s “nuanced discussion” concerning the subgroups. Clarifying the different levels of risk is critical for individuals who are weighing the decision whether to get future vaccine doses, she said.

Another key takeaway is that, for the population as a whole, risk didn’t increase with a third dose, Hanneman noted. “I think this is incredibly timely. It is based on limited data—there were very few patients who had received a third dose that were included, and that’s understandable of course. . . . [But] if you look at the data, the incidence of myopericarditis was about 10 times lower in their analysis after the third dose compared with the second.” This is consistent with the clinical experience at her center as well as with earlier reports on booster doses, she noted, adding that it’s possible the much longer interval between the second and third doses, as opposed to the first and second, could explain these results. It’s also possible, she acknowledged, that patients who experience the complication after dose two would then choose not to get dose three.

Trust is a ‘Fragile Commodity’

Margaret Ryan, MD, MPH (University of California San Diego and Defense Health Agency, Falls Church, VA) and Jay Montgomery, MD (Walter Reed National Military Medical Center, Bethesda, MD, and Defense Health Agency), write in accompanying editorial that this “study provides an important perspective on the historical global experience with cardiac adverse events after vaccination.”

They urge ongoing research to ascertain the pathophysiology of these events occurring after mRNA-based COVID-19 vaccines, especially given how little is known outside the realm of smallpox. “Reports of unexpected adverse events—albeit rare and limited to a specific subset of vaccine recipients—have the potential to damage vaccine confidence at a crucial point in the pandemic response,” Ryan and Montgomery say.

Even though the benefits of COVID-19 vaccines outweigh their risks, “scientific knowledge and public health strategies must continue to evolve,” they conclude. “Alternative vaccine platforms, vaccine doses, or vaccine schedules could reduce the risk of rare adverse events and must be explored in the context of changing infection risk. Vaccine confidence is one our most valuable resources, and it is dependent upon trust in public health. Trust is a fragile commodity that is strengthened by reporting challenges transparently and addressing these challenges with scientific rigor and appropriate concern.”

The sheer number of people getting the COVID-19 vaccines in such a short window of time is unprecedented, said Hanneman. Rare complications are easier to spot with such large numbers at play. As these reports emerge, “it’s very important that we report as transparently as possible, so people can make informed decisions,” she advised.

For her, the most pressing area of study is what happens to patients after they experience vaccine-related myopericarditis. Most recover quickly, but only further research can show whether there are any effects on long-term prognosis. Beyond their clinical outcomes, said Hanneman, there’s the question of “Is there any residual scarring?” The MYOVAX study, for which she’s principal investigator, is looking deeper into that issue.