Institute for Health & Care Transformation (IHCT)
for continuous transformation & digital health
Joaquim Cardoso MSc
Founder and Chief Researcher & Editor
December 22, 2022
Executive Summary
By Daniel Goldstein, MD on his linkedin post
In this winter solstice, with its shrinking daylight and artic blasts firmly in the horizon, the latest data published in JAMA Pediatrics — seeking to advance our knowledge in this highly frictional topic.
Vaccine-induced myopericarditis — and there is ZERO doubt of this causality — has squarely focused on young males who received mRNA vaccination. To the credit of this publication, the authors zeroed on this very population rather than expand it to all age groups where this complication is extremely uncommon.
The totality of this meta analysis which includes 23 studies and 854 adolescents came to the very same conclusions I have been sharing all along with you in more than 20 posts on the subject:
- It is rare 0.3–5 per 100,000 people (likely higher than that but asymptomatic in many instances);
- it is overwhelmingly seen in males after 2nd dose.
- It is characterized by high troponins, chest pain and gadolinium enhancement;
- it is short-lived (hospital length of stay < 3days),
- does NOT require special treatments;
- it is extremely unlikely to impact left ventricular function (almost no inotrope use and NO mechanical circulatory support required), and
- it is NOT associated with any deaths.
Long term follow up is not described but it is being investigated here by the CDC (https://lnkd.in/eZ5JCPvY).
Important study that summarizes what we know (demographics and clinical course ) and what we don’t know — why it happens in males and what is the underlying mechanism causing inflammation of the myocardium.
https://www.linkedin.com/feed/update/urn:li:activity:7011507070680072193/
ORIGINAL PUBLICATION
Myopericarditis After COVID-19 mRNA Vaccination Among Adolescents and Young Adults A Systematic Review and Meta-analysis
JAMA Network
Jun Yasuhara, MD1,2; Kaihei Masuda, MD3; Tadao Aikawa, MD, PhD4; Takuro Shirasu, MD, PhD5; Hisato Takagi, MD, PhD6; Simon Lee, MD2; Toshiki Kuno, MD, PhD7
December 5, 2022
KEY POINTS
Question
- What are the frequency, clinical features, and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in adolescents and young adults?
Findings
- In this systematic review and meta-analysis of 23 studies, including 854 patients aged 12 to 20 years with vaccine-associated myopericarditis, the incidence of myopericarditis was higher in males after the second dose.
- Although 15.6% of patients had left ventricular (LV) systolic dysfunction, only 1.3% had severe LV systolic dysfunction (ejection fraction ❤5%);
- late gadolinium enhancement was found in 87.2% and 23.2% required intensive care unit admission;
- however, no in-hospital mortality was observed.
Meaning
- These findings suggest largely favorable outcomes of COVID-19 vaccine-associated myopericarditis in adolescents and young adults.
ABSTRACT
Importance
- Published data on COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults have been derived from small case series, national population-based studies, or passive reporting systems.
- Pooled evidence from a larger, international cohort is scarce.
Objective
- To investigate the clinical features and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in a heterogeneous population of adolescents and young adults.
Data Sources
- PubMed and EMBASE were searched through August 2022. Language restrictions were not applied.
Study Selection
- Observational studies and case series describing COVID-19 vaccine–associated myopericarditis in adolescents and young adults aged 12 to 20 years and reporting clinical characteristics and early outcomes were included.
Data Extraction and Synthesis
- Two independent investigators extracted relevant data from each study.
- One-group meta-analysis in a random effects model was performed.
- The Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed.
Main Outcomes and Measures
- The primary outcomes were clinical features and early outcomes for COVID-19 mRNA vaccine–associated myopericarditis, including incident rate, cardiac findings, hospitalization, intensive care unit (ICU) admission, and in-hospital mortality.
Results
- A total of 23 observational studies were identified, including 854 individuals (mean age, 15.9 [95% CI, 15.5–16.2] years) with COVID-19 vaccine–associated myopericarditis.
- Male sex was predominant, at 90.3% (95% CI, 87.3%-93.2%) of individuals.
- The incident rate was higher after the second dose than the first dose, with 74.4% (95% CI, 58.2%-90.5%) of events occurring after the second dose.
- Most patients (84.4% [95% CI, 80.5%-88.3%] of patients) had preserved left ventricular (LV) function.
- Of the 15.6% (95% CI, 11.7%-19.5%) of patients with LV systolic dysfunction (LV ejection fraction [LVEF] <55%), most (14.1% [95% CI, 10.2%-18.1%]) were mild (ie, LVEF 45%-54%), and only 1.3% (95% CI, 0%-2.6%) of patients had severe LV systolic dysfunction (ie, LVEF❤5%). Interestingly, cardiac magnetic resonance imaging revealed late gadolinium enhancement in 87.2% (95% CI, 79.8%-94.7%) of patients.
- Although 92.6% (95% CI, 87.8%-97.3%) of patients were hospitalized and 23.2% (95% CI, 11.7%-34.7%) of patients required ICU admission, inotropes were used in only 1.3% (95% CI, 0%-2.7%) of patients, no patients died or required mechanical support, and the hospital length of stay was 2.8 (95% CI, 2.1–3.5) days.
Conclusions and Relevance
- This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations.
- These findings are reassuring but continued follow-up is warranted.
This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations.
These findings are reassuring but continued follow-up is warranted.
Introduction
The COVID-19 global pandemic began in December 2019.1 The introduction of the messenger RNA (mRNA) vaccine against SARS-CoV-2 has resulted in a significant decline in COVID-19–related morbidity and mortality all over the world.2–4
COVID-19 mRNA vaccines are the current standard approach to contain the pandemic and the Emergency Use Authorizations for these vaccines were recently extended to children aged 6 months and older in the US.
Since the emergency use was authorized, the association of the mRNA-based COVID-19 vaccine with myopericarditis, which is a rare but serious adverse event, has been reported.5,6
Cases of myopericarditis following COVID-19 mRNA vaccination have been reported worldwide, especially in adolescents and young adults.
In addition, in June 2021, the Centers for Disease Control and Prevention (CDC) observed a rate of postvaccine myopericarditis that was higher in young males after the second mRNA vaccine doses.7
Previous studies reported largely favorable outcomes in adults with myocarditis following COVID-19 mRNA vaccination, demonstrating resolution of clinical symptoms, preservation of cardiac function, and no complications.8–11
However, data on the clinical features and outcomes of myopericarditis after COVID-19 vaccination in adolescents and young adults are scarce compared with adults and often consist of small case series.
Most large-scale studies on COVID-19 vaccine–associated myopericarditis among adolescents and young adults are derived from national population-based studies that contain homogeneous populations or from surveillance networks that rely on passive reporting.
In this study, we conducted a systematic review and meta-analysis to investigate the clinical spectrum and outcomes of COVID-19 vaccine–associated myopericarditis in adolescents and young adults from an international population.
Methods & other sections
See the original publication (this is an excerpt version)
Discussion
This systematic review and meta-analysis comprehensively summarized the available published literature and assessed the current situation regarding myopericarditis after COVID-19 vaccination in adolescents and young adults across a wide range of populations.
There are 4 main findings of our study.
- First, COVID-19 vaccine–associated myopericarditis was predominantly observed in males after the second dose.
- Second, LV systolic dysfunction was identified in 15.6% of the patients; however, only 1.3% of patients had severe LV systolic dysfunction.
- Third, CMR showed LGE in 87.2% of patients.
- Fourth, although more than 90.0% of patients were hospitalized and 23.2% of patients were admitted to the ICU, inotropes were used in only 1.3% of patients, the duration of hospitalization was 2.8 days, and no patients died or required mechanical support during the hospitalization.
These findings are consistent with results from previous studies in adults, in which clinical course of COVID-19 vaccine–associated myopericarditis was typically mild, with complete resolution of symptoms and LV systolic dysfunction at presentation normalized within a few days.44
Furthermore, recent systematic reviews have summarized the rate and clinical characteristics of myopericarditis after COVID-19 vaccination in children and adolescents (age <19 years).45,46
They reported that echocardiographic findings were often normal, including pericardial effusion and borderline or mild depressed LV systolic function, and most patients recovered, with very few deaths reported.
In contrast, compared with these reviews, the novelty of our study lies on providing the pooled estimates across the published observational studies with a wide range of international population using 1-group meta-analysis.
In particular, more detailed and specific data focusing on the clinical characteristics and outcomes, such as LV systolic dysfunction (mild, moderate, or severe), presence of LGE, myocardial edema, hospitalization, ICU admission, and hospital length of stay would be useful for a broad range of physicians as well as parents.
The overall incidence of COVID-19 mRNA vaccine–associated myocarditis was reported to be low, estimated as 0.3 to 5.0 cases per 100 000 vaccinated people in case series studies from the US and Israel.47–50
Myocarditis occurred primarily after the second vaccination in young males (1 case per 12 361 individuals in male adolescents vs 1 case per 144 439 individuals in female adolescents; 0.56 cases per 100 000 individuals after the first dose vs 8.09 cases per 100 000 individuals after the second dose in males).48
Within the ages of 12 to 17 years, males were 7.2 times more likely to develop myocarditis following COVID-19 vaccination compared with females and myocarditis incidence was 6.8 times higher after the second dose than the first dose.51
Our results are consistent with these reports, suggesting that myocarditis incidence after COVID-19 mRNA vaccination is rare and occurred mainly after the second dose in males.
The incidence of myocarditis appears to be different among mRNA vaccines. In our study, almost all the cases of myocarditis were seen after the BNT162b2 vaccine.
In contrast, a higher risk of myocarditis with mRNA-1273 compared with BNT162b2 has been observed in large observational studies.52–54
Importantly, the risk of developing myocarditis after SARS-CoV-2 infection is significantly higher than after COVID-19 mRNA vaccination.
The incidence of myocarditis after SARS-CoV-2 infection is higher than after COVID-19 mRNA vaccination (11.0 events per 100 000 persons vs 3.2 events per 100 000 persons).55
Furthermore, compared with cardiac complications associated with COVID-19, our study revealed largely favorable early outcomes of vaccine-associated myopericarditis.56
Accordingly, the benefits of the mRNA COVID-19 vaccination are deemed to outweigh the potential risks.
Despite the lack of severe complications commonly associated with COVID-19 mRNA vaccination, vaccine hesitancy remains high, and some parents still hesitate to vaccinate their children against COVID-19.57
Our findings corroborate the relatively low risks and good early outcomes for COVID-19 vaccine–associated myopericarditis across a wide population from multiple counties, improving understanding of myopericarditis following COVID-19 mRNA vaccination among adolescents and young adults and decision-making for parents with vaccine hesitancy.
The use of CMR is important in the noninvasive diagnosis and risk stratification of myocarditis.
In particular, T2-weighted imaging is routinely performed to detect acute myocardial inflammation or edema.
Similarly, LGE is widely used to detect necrosis and fibrosis and is incorporated into the original and revised Lake Louise criteria for diagnosis of acute myocarditis.
In our study, the Lake Louise Criteria was used, and CMR was performed for making the diagnosis of myocarditis.
However, a large proportion of patients with subclinical myocarditis might not have been diagnosed with myocarditis, leading to much lower hospitalization and ICU admission rates than currently reported.
This would strengthen the argument that most cases of myocarditis are mild and possibly even underdiagnosed.
Interestingly, our study found LGE in 87.2% of adolescents and young adults, while the clinical course was mild and no in-hospital mortality was observed. Although a previous study also detected LGE in 88.3% of patients (aged 14–70 years) with myocarditis after COVID-19 mRNA vaccination, all patients recovered and were discharged.9
Unfortunately, the degree and extent of LGE was not reported, and follow-up studies with CMR have not been published, to our knowledge.
The persistence of LGE indicates the potential myocardial fibrosis and could be a risk factor for adverse cardiac events, including arrhythmias, cardiac dysfunction, or recurrent myocarditis, in patients with myocarditis due to other causes.58
While this is similar to other, non–vaccine-associated myocarditis, a clinical follow-up of cardiovascular events in patients with vaccine-associated myocarditis is essential.
Further studies are needed to investigate the association of CMR findings and long-term outcomes.
Limitations
This study had several limitations to be noted.
First, the available studies were observational studies or case series, subject to methodological biases or publication biases.
Second, each study contained a small number of patients, potentially leading to substantial heterogeneity.
Additionally, we excluded case reports, which may have included severe cases not reported in large observational studies. Furthermore, the retrospective designs of the included studies might have underestimated the complications.
Third, it is difficult to identify a small number of overlaps in patient data between multicenter studies from the same countries, although we removed 1 study from Hong Kong and 2 single-center studies from the US that were likely to have overlapping patient data with other studies.
Fourth, the lack of universal case inclusion criteria or diagnostic tests could lead to a misdiagnosis or underreporting of vaccine-associated myocarditis.
Fifth, several variables were not available.
For example, whereas an 8-week or longer interval has been associated with a lower risk of myopericarditis associated with COVID-19 mRNA vaccines in a population-based cohort study,59 these variables were not obtainable across the included studies; the influence of the interval in adolescents and young adults remains uncertain.
Sixth, our study did not find the association of symptoms with unfavorable outcomes in adolescents and young adults.
Although a previous study reported that adult patients with gastrointestinal symptoms received more intensive care, risk factors of poor prognosis remain elusive.60
Seventh, in this study, most of the types of vaccine were BNT162b2 vaccines, limiting the generalizability of findings to other COVID-19 vaccines, including the mRNA-1273 vaccine.
Conclusions
The findings of this systematic review and meta-analysis pooling data from multiple countries demonstrate low incidence rate and largely favorable early outcomes of COVID-19 vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations.
While mortality data are reassuring, a significant number of patients were reported to have acute LGE.
Our findings could help improve understanding of myopericarditis among adolescents and young adults and decision-making for parents.
Authors affiliations
Center for Cardiovascular Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio (Yasuhara); The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio (Yasuhara, Lee); Department of General Internal Medicine, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan (Masuda); Department of Cardiology, Hokkaido Cardiovascular Hospital, Sapporo, Japan (Aikawa); Division of Vascular and Endovascular Surgery, Department of Surgery, School of Medicine, University of Virginia, Charlottesville (Shirasu); Division of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan (Takagi); Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York (Kuno).
References
See the original publication
Originally published at https://jamanetwork.com
