Studies of mRNA-based COVID-19 vaccines have shown they are frequently associated with mild adverse effects in the first 24–48 h after administration, including pain and swelling at the injection site, fatigue, headache, muscle pain, chills, fever, and nausea [13]. While more severe adverse effects following COVID-19 vaccination are rare, they can occur.

In this case series, we provide detailed clinical and cardiovascular imaging findings in five young adult male patients with acute myocarditis following mRNA COVID-19 vaccination. With respect to the CMR findings in our patients, all five patients met the updated 2018 Lake Louise CMR criteria for acute myocarditis [14]. Interestingly, LGE and myocardial edema in our patients predominantly localized to the basal and mid lateral LV segments. Such distribution of myocardial edema and LGE on CMR was similarly seen in other case series of adults and pediatric population [5,6,7,8,9,10, 15, 16]. Prior studies suggest that this distribution of LGE carries a better prognosis compared to LGE localized to the septal segments [17].

Our case series adds to a growing number of recently published case series suggesting a possible association between acute myocarditis and mRNA COVID-19 vaccination, predominantly in males younger than 40 years of age. In the largest such series, by Montgomery et al., only 8 of the 23 patients (all males aged 20–51 years) underwent CMR [9]. Among these 8, all met Lake Louise CMR criteria for acute myocarditis but the specific pattern and location of LGE was not reported [9]. Similarly, Larson et al. described ‘patchy’ LGE in 8 healthy males aged 21 to 56 years diagnosed with acute myocarditis 2–4 days after receiving COVID-19 vaccination but again a more specific pattern was not described [8]. Other case series by Rosner et al., Shaw et al., Dickey et al. and Kim et al. found a pattern on CMR identical to the one we describe in our series [5,6,7, 10]. An additional case series by Marshall et al. found similar CMR findings in 7 adolescent male patients, suggesting that CMR findings in this clinical scenario may occur across age groups [11].

Consistent with previously published case series, all of our patients were males younger than 40 years. According to the CDC’s Advisory Committee on Immunization Practices, as of June 11, 2021, there have been 52 million doses of mRNA-based COVID-19 administered in persons aged 12–29 years and within this group there have been only 323 confirmed cases of myocarditis, pericarditis, or myopericarditis [18]. Among these 323 patients, the median age was 19 years, 291 (90%) were males, and the median interval from vaccination to symptom onset was 2 days [18]. From previous literature, it also appears that myocarditis typically occurs more commonly in males, and the incidence is highest amongst adolescent and young adults [19, 20]. The underlying pathophysiologic mechanism(s) of higher prevalence of acute myocarditis in males is poorly understood, but limited data suggest that elevated testosterone can contribute to acute myocarditis is by increasing viral binding to myocytes [21], inhibiting anti-inflammatory cell population [22], and upregulating cardiac fibrotic remodeling genes [23]. On the other hand, estrogen may play a protective role in myocarditis by stimulating inhibitory T regulator cells and inhibiting proinflammatory T-cells [23, 24].

If in fact there is a causal relationship between COVID-19 vaccination and acute myocarditis in this patient population—which this case series does not definitively establish—the underlying mechanism is unclear at this time. Rare cases of myocarditis have been reported after vaccinations for other diseases. Myocarditis and pericarditis have been reported after smallpox vaccination, and endomyocardial biopsy in such cases has suggested an immunological mediated etiology [25]. Because SARS-CoV-2 infection results a hyperinflammatory host response, it is plausible that vaccination stimulates in rare cases a similar immune response with direct cardiac effects.

Two-dimensional speckle tracking with echocardiography and feature-tracking with CMR can quantitatively measure myocardial mechanics (strain) in the longitudinal direction; and a decrease in GLS has been shown to detect LV dysfunction before a reduction in LVEF is identified [26]. Interestingly, three of our five patients had reduced or borderline reduced GLS. In acute myocarditis, reduced LV strain has shown to be predictive of adverse outcomes, even in patients with preserved LVEF [27]. Longer clinical follow-up may help understand if the CMR abnormalities observed are temporary in the setting of a high inflammatory state or longer-lasting, and whether they help predict any clinically-relevant adverse events or deterioration in cardiac function.

In the state of Rhode Island, a total of 693,578 people have received COVID-19 vaccination with at least one dose and a total of 635,432 people are fully vaccinated against COVID-19 infection [28]. This case series suggest that the estimated prevalence of acute myocarditis following COVID-19 vaccination is very low, but physicians should be vigilant in diagnosing such patients who are presenting with chest pain following COVID-19 vaccinations especially as we expand COVID-19 vaccination to more younger population. While, per CDC’s Advisory Committee on Immunization Practices, as of June 11, 2021, 96% of these patients were hospitalized, the vast majority had clinical courses similar to what we observed in all 5 of our patients—no deaths, resolution of symptoms with non-steroidal anti-inflammatory drugs, and relatively short hospital stays [18]. Nevertheless, continued clinical follow-up of these patients, perhaps with repeat CMR in 3–6 months, is needed to better understand whether there are any meaningful medium- and long-term effects of myocarditis following mRNA COVID-19 vaccination.

Limitations

Given this is a small case series from a single tertiary center in the state of Rhode Island, it is important to highlight that we cannot provide causal relationship and in fact only provides a possible association of acute myocarditis with mRNA COVID-19 vaccination. We do not have a long term follow up data on these patients and unable to ascertain the relevance of acute myocarditis on potentially receiving a future booster dose of COVID-19 vaccination. Despite these limitations, it is notable that the clinical presentation and CMR findings in these patients appear consistent with previously published case series of acute myocarditis after receiving mRNA COVID-19 vaccination.