Dispelling concerns: the mild nature of coronavirus disease 2019 vaccine-related myocarditis

Coronavirus disease 2019 (COVID-19) has become established as a major cause of morbidity and mortality worldwide [1]. While primarily targeting the respiratory system [2], extra-pulmonary manifestations due to direct viral entry, immune dysregulation, and clotting and vascular dysfunction are widely reported [3].

Acute myocarditis has been documented in subsets of patients with COVID-19, often in the context of severe systemic illness, with incidence estimated at 2 to 4 per 1000 in patients hospitalized for COVID-19 [4]. Epidemiologic studies from multiple settings indicate at least a 15-fold greater risk of acute myocarditis after COVID-19 compared to other causes [5], suggesting a potential distinct mechanistic relationship. The occurrence of COVID-19-related myocarditis is associated with greater hemodynamic instability and poorer clinical outcomes [4].

The emergence of COVID-19 vaccines represented a transformative step change in the course of the pandemic with the possibility to reduce the rate and severity of infection across whole populations. While myocarditis had not been observed in COVID-19 vaccine clinical trials, reports of this adverse event emerged with mass roll-out across the world. Initial case reports [6] were subsequently corroborated by large database analyses, indicating a heightened risk of acute myocarditis after COVID-19 vaccination which appeared greatest with mRNA vaccines, after the second dose, and in adolescent and younger males [7], [8], [9]. Most studies report a relatively benign course over the first 7 to 30 days of follow-up [7], [10], with few studies considering longer-term outcomes.

Cardiovascular magnetic resonance (CMR) is the imaging modality of choice for the evaluation of acute myocarditis, providing a unique non-invasive assessment of myocardial tissue character, which directly informs established Lake Louise diagnostic criteria [11] and is recommended for evaluation of myocarditis in the setting of COVID-19 [12]. In unselected cohorts, CMR scanning after COVID-19 vaccination did not reveal evidence of myocardial inflammation or injury providing reassurance that subclinical myocarditis is not a phenomenon universally experienced by all vaccine recipients [13]. While characteristic CMR abnormalities have been reported in the context of COVID-19 vaccine-related myocarditis [6], the prognostic relevance of these findings is not known.

To assess the clinical and public health risk of COVID-19 vaccine-related myocarditis, it is essential to capture its entire natural history and to fully understand the prognostic implications of the condition. The study by Talib et al. [14] elegantly addresses these major gaps in clinical knowledge, presenting the longest follow-up duration reported to date and, uniquely, tracking CMR alterations through interval scanning of affected patients. The research comprises a retrospective single-center study of 89 consecutive patients undergoing CMR for suspected COVID-19 vaccine-related myocarditis. Among these, 42 patients had at least one CMR abnormality and 25 met both T1 and T2 diagnostic criteria for acute myocarditis. In the latter group, 21 patients underwent repeat CMR scanning after a median of 214 (interquartile range [IQR] 132–304) days, demonstrating resolution of myocardial edema and normalization of left ventricular ejection fraction with only minimal residual late gadolinium enhancement in 48% (10/21) of patients. There were no adverse clinical events reported across 232 (IQR 156–405, n = 60) days of follow-up.

The study by Talib et al. [14] corroborates past reports of COVID-19 vaccine-related myocarditis and demonstrates, for the first time, the relatively benign nature of this phenomenon throughout its complete clinical course. The work also contributes important new information to the literature by demonstrating interval resolution of almost all CMR abnormalities in individuals affected by vaccine-related myocarditis.

Multicenter reports to better capture the entire spectrum of COVID-19 vaccine-related myocarditis with prospective follow-up, and studies of special populations (e.g., pregnancy, adult congenital heart disease) in whom the consequences of vaccine-related myocarditis may be more important are warranted.

It is important to emphasize that the excess risk of myocarditis after COVID-19 infection is far greater than that after vaccination (1 to 6 vs 40 per 1 million people) [10], as are the adverse prognostic consequences. Despite this, reports of COVID-19 vaccine-related myocarditis have led to substantial concern among clinicians and the public, contributing to vaccine hesitancy across many groups, in particular young males. This experience has important lessons for the scientific community highlighting the importance of universal standardization of vaccine safety protocols, systematic evaluation of reported adverse events, and transparent science communication to mitigate potentially damaging misconceptions.

The study by Talib et al. [14] is an important contribution to extending knowledge in this area and goes a long way in providing further reassurance about the safety of COVID-19 vaccination for patients, clinicians, and public health providers.

Funding

Z.R.E. recognizes the National Institute for Health and Care Research (NIHR) Integrated Academic Training program which supports her Academic Clinical Lectureship post.

Declaration of competing interests

The author declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.