Cardiac MRI Findings of Myocarditis After COVID-19 mRNA Vaccination in Adolescents

Chelala, Lydia; Jeudy, Jean; Hossain, Rydhwana; Rosenthal, Geoffrey L.; Pietris, Nicholas; White, Charles S.

doi:10.2214/ajr.21.26853

Cited by 34 publications

(49 citation statements)

References 13 publications

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“…It is possible that these patients reflect the more severe end of the spectrum of vaccine-associated myocardial changes due to reporting bias. Typical cardiac MRI findings reported to date in patients with myocarditis following COVID-19 vaccination are similar to findings in nonvaccine myocarditis, including subepicardial LGE with a predilection for the basal inferolateral wall along with corresponding myocardial edema ( Fig 6 ) ( 41 – 51 ). Other findings include pericardial enhancement and axillary lymphadenopathy ipsilateral to the vaccine administration site ( 52 ).…”

Section: Cardiac Mri In Specific Causes Of Myocarditissupporting

confidence: 68%

Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination

Tijmes

Thavendiranathan

Udell

et al. 2021

Radiology: Cardiothoracic Imaging

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Myocarditis is a nonischemic inflammatory disease of the myocardium that can be triggered by a multitude of events, including viral infection and toxins. Recently, there has been heightened interest in myocarditis given its association with COVID-19 vaccination. Timely identification of myocarditis can affect patient management and prognosis. Therefore, it is crucial for radiologists and cardiac imagers to understand the role of cardiac imaging to establish a diagnosis and inform treatment decisions. Cardiac MRI is the most important noninvasive imaging modality for evaluation of myocarditis, with typical findings of focal or diffuse myocardial edema and myocardial damage, including presence of late gadolinium enhancement. There are currently limited data available to indicate that the pattern of myocardial injury following COVID-19 vaccination is similar to other causes of myocarditis, although the severity of disease may be relatively mild. A description of the role of imaging and typical imaging features will be reviewed here, with a focus on emerging data in the setting of myocarditis after COVID-19 vaccination. Keywords: MRI, Heart, Inflammation © RSNA, 2021

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Section: Cardiac Mri In Specific Causes Of Myocarditissupporting

confidence: 68%

Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination

Tijmes

Thavendiranathan

Udell

et al. 2021

Radiology: Cardiothoracic Imaging

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“…25–28 31–36 ). From the search update, we identified 34 new reports across all questions (Q1=9 37–45 , Q2=5 37 41 45–47 , Q3=1 48 , Q4=3 39 49 50 , Q5=21 9 51–70 ); we excluded five studies that only reported on combined myo- and/or pericarditis (as we located other studies with these reported separately), 71–75 eight studies that did not report on confirmed cases, 76–83 and three studies 84–86 that did not contribute additional data to other included studies on the same cases. Tables of study characteristics, with all data on results, and risk of bias ratings for questions 1 and 2 are in Appendix 2.…”

Section: Resultsmentioning

confidence: 99%

“…Three reports 39 49 50 reported on 38 cases with follow-up approximately 90 days after diagnosis of myocarditis following vaccination with an mRNA COVID-19 vaccine ( Table 6 ). Among 14 patients hospitalized for myocarditis after vaccination in the two smaller case series (n=14), patients were males aged 13-19 years and followed up for ∼90-105 days after diagnosis.…”

Section: Resultsmentioning

confidence: 99%

“…Among 14 patients hospitalized for myocarditis after vaccination in the two smaller case series (n=14), patients were males aged 13-19 years and followed up for ~90-105 days after diagnosis. In the case series of five patients, 49 repeat cardiac MRI was undertaken in two patients, with both showing persistent but decreased late gadolinium enhancement similar to the distribution of the initial MRI but no new abnormalities. Further, three patients had self-resolving mild intermittent chest pain after discharge, one had recurrent chest pain after discontinuing the NSAID prescribed at discharge, and three had recurrent symptoms that prompted emergency department visits post-discharge.…”

Section: Question 4 Longer-term Outcomesmentioning

confidence: 99%

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Myocarditis and Pericarditis following COVID-19 Vaccination: Evidence Syntheses on Incidence, Risk Factors, Natural History, and Hypothesized Mechanisms

Pillay

Gaudet

Wingert

et al. 2022

Preprint

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ObjectivesMyocarditis and pericarditis are adverse events of special interest after vaccination for COVID-19. Evidence syntheses were conducted on incidence rates, risk factors for myocarditis and pericarditis after COVID-19 mRNA vaccination, clinical presentation and short- and longer-term outcomes of cases, and proposed mechanisms and their supporting evidence.DesignSystematic reviews and evidence reviews.Data sourcesMedline, Embase and the Cochrane Library were searched from October 2020 to January 10, 2022; reference lists and grey literature (to January 13, 2021).Review methodsLarge (>10,000) or population-based/multisite observational studies and surveillance data (incidence and risk factors) reporting on confirmed myocarditis or pericarditis after COVID-19 vaccination; case series (n≥5, presentation, short-term clinical course and longer-term outcomes); opinions/letters/reviews/primary studies focused on describing or supporting hypothesized mechanisms. A single reviewer completed screening and another verified 50% of exclusions, using a machine-learning program to prioritize records. A second reviewer verified all exclusions at full text, extracted data, and (for incidence and risk factors) risk of bias assessments using modified Joanna Briggs Institute tools. Team consensus determined certainty of evidence ratings for incidence and risk factors using GRADE.Results46 studies were included (14 on incidence, 7 on risk factors, 11 on characteristics and short-term course, 3 on longer term outcomes, and 21 on mechanisms). Incidence of myocarditis after mRNA vaccines is highest in male adolescents and young adults (12-17y: range 50-139 cases per million [low certainty] and 18-29y: range 28-147 per million [moderate certainty]). For 5-11 year-old males and females and females 18-29 years of age, incidence of myocarditis after vaccination with Pfizer may be fewer than 20 cases per million (low certainty). There was very low certainty evidence for incidence after a third dose of an mRNA vaccine. For 18-29 year-old males and females, incidence of myocarditis is probably higher after vaccination with Moderna compared to Pfizer (moderate certainty). Among 12-17, 18-29 and 18-39 year-olds, incidence of myocarditis/pericarditis after dose 2 of an mRNA vaccine may be lower when administered ≥31 days compared to ≤30 days after dose 1 (low certainty). Data specific to males aged 18-29 indicated that the dosing interval may need to increase to ≥56 days to substantially drop incidence. For clinical course and short-term outcomes only one small series (n=8) was found for 5-11 year olds. In cases of adolescents and adults, the majority (>90%) of myocarditis cases involved 20-30 year-old males with symptom onset 2 to 4 days after second dose (71-100%). Most cases were hospitalized (≥84%) for a short duration (2-4 d). For pericarditis, data is limited but more variation has been reported in patient age, sex, onset timing and rate of hospitalization. Case series with longer-term (3 mo; n=38) follow-up suggest persistent ECG abnormalities, as well as ongoing symptoms and/or a need for medications or restriction from activities in >50% of patients. 16 hypothesized mechanisms are described, with little direct supporting or refuting evidence.ConclusionsAdolescent and young adult males are at the highest risk of myocarditis after mRNA vaccination. Pfizer over Moderna and waiting more than 30 days between doses may be preferred for this population. Incidence of myocarditis in children aged 5-11 may be very rare but certainty was low. Data on clinical risk factors was very limited. Clinical course of mRNA related myocarditis appears to be benign although longer term follow-up data is limited. Prospective studies with appropriate testing (e.g., biopsy, tissue morphology) will enhance understanding of mechanism(s).Funding and Registration noThis project was funded in part by the Canadian Institutes of Health Research (CIHR) through the COVID-19 Evidence Network to support Decision-making (COVID-END) at McMaster University. Not registered.Summary boxWhat is already known about this topic?Case reports and surveillance signals of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the two-layered sac surrounding the heart) after COVID-19 vaccination appeared as early as April 2021.These have prompted ongoing surveillance and research of these complications to investigate their incidence, possible attribution to the vaccines, and clinical course.What this study addsThis review critically appraises and synthesizes the available evidence to-date on the incidence of and risk factors for myocarditis and pericarditis after COVID-19 vaccination in multiple countries. It summarizes the presentation and clinical course of over 8000 reported cases and describes some initial reports of longer term outcomes. Further, many possible mechanisms are outlined and discussed.Though low, the incidence of myocarditis is probably the highest in young males aged 12-29 years and is probably higher with Moderna than Pfizer mRNA vaccines. Longer dosing intervals may be beneficial. Most cases are mild and self-limiting, though data in 5-11 year-olds is very limited. Continued active surveillance with longer term follow-up is warranted.

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“…Notably, cases falling out of this typical age- and time-pattern have been reported [ 17 ]. Cardiac enzyme elevations are universally observed and may be accompanied by corresponding electrocardiographic changes [ 14 ], while the findings in cardiac MRI do not differ from those of myocarditis due to other causes [ 18 ]. The clinical course is typically benign and rapidly self-limiting, although cases with a more severe course including a significant left ventricular dysfunction or even death have been reported [ 14 , 16 ].…”

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confidence: 99%

Potential implications of lipid nanoparticles in the pathogenesis of myocarditis associated with the use of mRNA vaccines against SARS-CoV-2

et al. 2022

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Although mRNA-based vaccines BNT162b2 and mRNA-1273 exhibit a remarkable efficacy and effectiveness in preventing particularly severe Covid-19 with an overall favorable adverse event profile, their use has been associated with rare cases of acute myocarditis. These occur most commonly after the second dose, with the highest incidence among young male recipients. This complication has not been observed among adenoviral vector vaccine receivers, and its clinical, laboratory and imaging features resemble those of other common causes of acute myocarditis. The pathogenesis of mRNA-vaccine associated myocarditis has not yet been elucidated, although a number of mechanisms have been proposed, typically implicating the administered S-protein mRNA and likely mediated through an autoimmune mechanism. Nonetheless, other mechanisms may be implicated given the fact that myocarditis cases are very rarely observed among recipients of non mRNA vaccines. The recent observation of a similar adverse event in a recipient of the non-mRNA, peptide-based NVX-CoV2373 in the frame of a phase III clinical trial with 7020 participants in the active treatment arm raises the question whether the lipid nanoparticle sheath, which is a common structural component of these platforms could be implicated in the pathogenesis of vaccine-induced myocarditis.

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Cardiac MRI Findings of Myocarditis After COVID-19 mRNA Vaccination in Adolescents

Cited by 34 publications

References 13 publications

Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination

Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination

Myocarditis and Pericarditis following COVID-19 Vaccination: Evidence Syntheses on Incidence, Risk Factors, Natural History, and Hypothesized Mechanisms

Potential implications of lipid nanoparticles in the pathogenesis of myocarditis associated with the use of mRNA vaccines against SARS-CoV-2

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