Acute Myocarditis After COVID-19 Vaccination: A Nationwide Study in Korea Reveals Clinically Important Findings

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Cases of myocarditis and pericarditis have rarely been observed following receipt of COVID-19 vaccines used in the United States. Evidence from multiple monitoring systems in the United States and around the globe support a causal association between mRNA COVID-19 vaccines (i.e., Moderna or Pfizer-BioNTech) and myocarditis and pericarditis.

Myocarditis is inflammation of the heart muscle, and pericarditis is inflammation of the lining outside the heart; myopericarditis is present when both myocarditis and pericarditis occur at the same time.  In these conditions, inflammation occurs in response to an infection or some other trigger. CDC has published case definitions for myocarditis and pericarditis. The severity of cases of myocarditis and pericarditis can vary. CDC has published studies with clinical information about myocarditis and pericarditis after COVID-19 vaccination.

Cases of myocarditis and pericarditis have occurred most frequently in adolescent and young adult males within 7 days after receiving the second dose of an mRNA COVID-19 vaccine; however, cases have also been observed after dose 1 and booster doses.

Data from the clinical trials of the Novavax COVID-19 Vaccine and global vaccine safety monitoring systems suggest an increased risk of myocarditis and pericarditis following Novavax vaccination. Data from post-authorization monitoring of Janssen COVID-19 Vaccine (Johnson & Johnson) suggest a possible increased risk of myocarditis and pericarditis following Janssen vaccination.


Information on the clinical trials for the Novavax COVID-19 vaccine can be found here: U.S. clinical trial results show Novavax vaccine is safe and prevents COVID-19 | National Institutes of Health (NIH)

Information on the safety monitoring of the Janssen COVID-19 vaccine can be found here: Safety Monitoring of the Janssen (Johnson & Johnson) COVID-19 Vaccine — United States, March–April 2021 | MMWR (cdc.gov)


Understanding Myocarditis

Myocarditis is a heterogeneous condition that can affect individuals of all ages. It occurs when the myocardium becomes inflamed, leading to impaired heart muscle function. The inflammation can cause damage to the heart cells and disrupt the normal electrical signals, which regulate the heart’s rhythm. This can result in symptoms such as chest pain, fatigue, shortness of breath, and in severe cases, heart failure or sudden cardiac death.

Classification of Myocarditis

Myocarditis can be classified based on several factors, including the underlying cause, histological features, and clinical presentation. The World Health Organization (WHO) and the American Heart Association (AHA) have proposed different classifications for myocarditis:

  • Infectious Myocarditis: This type of myocarditis is caused by viral, bacterial, fungal, or parasitic infections. Viral infections, particularly enteroviruses and adenoviruses, are the most common culprits. COVID-19, caused by the SARS-CoV-2 virus, has also been associated with myocarditis in some cases.
  • Autoimmune Myocarditis: This form of myocarditis occurs when the body’s immune system mistakenly attacks the heart tissue. It is often associated with systemic autoimmune diseases such as lupus or rheumatoid arthritis.
  • Giant Cell Myocarditis: This rare and severe form of myocarditis is characterized by the presence of multinucleated giant cells in the heart tissue. Its exact cause is unknown, but it is believed to be related to an autoimmune response.
  • Lymphocytic Myocarditis: This type of myocarditis is characterized by infiltration of lymphocytes (a type of white blood cell) in the heart tissue. It is commonly associated with viral infections, including certain strains of Coxsackievirus and adenovirus.

Link Between COVID-19 Vaccines and Myocarditis

In recent months, there have been reports of myocarditis occurring after COVID-19 vaccination, particularly with mRNA vaccines, such as the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines. The association between COVID-19 vaccines and myocarditis is still being investigated, but several studies have provided insights into this potential link.

  • Incidence of Myocarditis After COVID-19 Vaccination: Multiple studies have reported cases of myocarditis following COVID-19 vaccination, albeit at a low incidence. The reported rates vary between studies, but they generally range from 1 to 10 cases per 100,000 vaccinated individuals. Notably, the incidence appears to be higher in younger males, particularly those between the ages of 16 and 30.
  • mRNA Vaccines and Myocarditis: The majority of myocarditis cases reported after COVID-19 vaccination have been associated with mRNA vaccines. The reasons for this association are still unclear. It is hypothesized that the immune response triggered by the vaccine, particularly in younger individuals with more robust immune systems, may contribute to the development of myocarditis.
  • Clinical Characteristics of Vaccine-Related Myocarditis: Vaccine-related myocarditis (VRM) typically presents within a few days after vaccination, usually after the second dose. Symptoms may include chest pain, shortness of breath, palpitations, and fatigue. While most cases of VRM have a mild clinical course and favorable outcomes, severe cases including death and fulminant myocarditis have been reported, although they are rare.
  • Sudden Cardiac Death and VRM: Recent studies have highlighted a potential association between COVID-19 VRM and sudden cardiac death (SCD), particularly in individuals under 45 years of age who have received mRNA vaccines. These cases of SCD are rare but concerning. It is crucial to note that the overall risk of SCD following COVID-19 vaccination is still extremely low compared to the risks associated with COVID-19 itself.

A recent nationwide study conducted in Korea involving over 44 million vaccinated individuals has shed light on the occurrence of acute myocarditis following COVID-19 vaccination.

The study highlights several crucial findings that have significant clinical implications

First, it reveals that vaccine-related myocarditis (VRM) is an extremely rare complication of COVID-19 vaccination, occurring at a rate of 1.08 cases per 100,000 vaccinated persons. Furthermore, the incidence of VRM was found to be primarily associated with mRNA vaccines, particularly in young males.

Second, the demographic characteristics of COVID-19 VRM cases in Korea differed from those observed in previous studies.

Third, the study uncovered a concerning revelation that severe cases of COVID-19 VRM, including fatalities and cases requiring intensive medical interventions such as extracorporeal membrane oxygenation (ECMO), were not uncommon, accounting for 19.8% of all VRM cases.

The study also identified sudden cardiac death (SCD) as a potentially fatal complication of COVID-19 vaccination, particularly in individuals under 45 years of age who had received mRNA vaccines. Lastly, the study showed a significant decrease in the incidence of severe VRM cases following the third COVID-19 vaccination.

Incidence of COVID-19 VRM

The nationwide Korean report revealed that the overall incidence of COVID-19 VRM was 1.08 cases per 100,000 vaccinated persons across all vaccines.

When considering specific vaccines, the incidence was 2.30 cases per 100,000 for mRNA-1273 and 1.23 cases per 100,000 for BNT162b2.

These figures align with previous studies, which reported varying incidences of myocarditis following COVID-19 vaccination, ranging from 1.4 to 5.0 cases per 100,000 vaccinated persons. Notably, a large cohort study in Israel identified VRM in 54 cases out of 2.5 million vaccinated individuals, with an estimated incidence of 2.13 cases per 100,000 vaccinated persons within 42 days after the first vaccine dose.

Similarly, analysis of the Vaccine Adverse Event Reporting System (VAERS) in the USA identified 1626 VRM cases out of 192,405,448 individuals vaccinated with COVID-19 mRNA vaccines. Another study conducted in Denmark reported an incidence of 1.4 cases per 100,000 vaccinated individuals with BNT162b2 and 4.2 cases per 100,000 with mRNA-1273 within 28 days of vaccination. These varying incidence rates may be attributed to differences in the COVID-19 vaccines used and the defined risk periods for myocarditis after vaccination. Ethnic differences might also contribute to the observed disparities.

Demographic Characteristics of COVID-19 VRM

Previous studies have suggested that COVID-19 VRM is more commonly associated with mRNA vaccines, particularly in young males, and tends to occur after the second dose of vaccination. The Korean study supports these findings, demonstrating a similar pattern of COVID-19 VRM development predominantly in young adult and adolescent males, primarily in association with mRNA vaccines.

However, the demographic characteristics of COVID-19 VRM cases in Korea differed in several aspects. Firstly, the male predominance observed in other populations was less pronounced among Koreans. Secondly, no significant difference in VRM incidence was observed between the first and second vaccination doses. Finally, COVID-19 VRM was found to be relatively common in individuals aged between 40 and 60 years, which deviates from the patterns observed in other studies.

Clinical Course and Severity of COVID-19 VRM

Prior studies have generally characterized COVID-19 VRM as a mild condition with favorable short-term clinical outcomes. However, the Korean study revealed a considerably different clinical course and severity of VRM. Among the total VRM cases, 19.8% were classified as severe, with 36 cases resulting in fatalities and 21 requiring ECMO. Most notably, the study identified eight cases of sudden cardiac death, which were only confirmed through autopsy and were all attributable to COVID-19 VRM. Importantly, all eight SCD cases occurred in individuals under 45 years of age who had received mRNA vaccines. These findings highlight the need for careful monitoring and warning of SCD as a potentially fatal complication of COVID-19 vaccination, particularly in young individuals receiving mRNA vaccines.

Limitations and Considerations

The study acknowledges several limitations. First, there is a possibility of underestimating the incidence of COVID-19 VRM due to the nature of the reporting system, despite efforts to reduce underreporting. Second, the diagnosis of myocarditis using the Boston Criteria may lead to both overreporting and underreporting. Modifications to the criteria and a more extensive evaluation, including cardiac imaging and biomarker assessments, are necessary to enhance diagnostic accuracy. Third, echocardiography and cardiac magnetic resonance imaging (CMR) findings were not available for all patients, which may limit the generalizability of these results. However, the presence of positive cardiac troponin results, along with robust symptoms of myocarditis, helped to strengthen the reliability of the diagnosis. Finally, the study did not include baseline characteristics of vaccinated individuals without VRM, limiting the ability to identify independent predictors for VRM in the entire vaccinated population.

Conclusion

The nationwide study in Korea provides important insights into the incidence and characteristics of acute myocarditis following COVID-19 vaccination. VRM was found to be a rare complication, predominantly associated with mRNA vaccines, and more common in young males. Although COVID-19 VRM often showed a favorable clinical course, severe cases including death and FM were not uncommon. The study’s most significant finding was the association between COVID-19 VRM and sudden cardiac death, particularly in individuals under 45 years of age who had received mRNA vaccines. These findings highlight the need for careful monitoring and warnings regarding severe COVID-19 VRM as a potentially fatal complication of COVID-19 vaccination, especially in young individuals. Efforts to minimize underreporting and establish robust diagnostic criteria should be prioritized to better understand and manage this rare adverse event.


reference link :https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehad339/7188747?login=false#407214790

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9419896/

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