Unlocking the Heart of the Matter: Understanding Myocarditis Risk After COVID-19 Vaccine Boosters

The development and global distribution of mRNA-based COVID-19 vaccines have been a remarkable achievement in the fight against the SARS-CoV-2 pandemic. These vaccines have not only demonstrated remarkable effectiveness in preventing severe illness and death but have also played a crucial role in controlling the spread of the virus, even as new variants have emerged. However, the success of these vaccines has not been without its challenges, and one such concern has been the reports of myocarditis and pericarditis following vaccination with mRNA-based COVID-19 vaccines, particularly the BNT162b2 vaccine.

Myocarditis and pericarditis are inflammatory conditions affecting the heart muscle and the lining around the heart, respectively. Myocarditis can be serious, leading to chest pain, shortness of breath, and in severe cases, heart failure although the reports after vaccination have generally been mild. In the United Kingdom, a self-controlled case series (SCCS) analysis was conducted to examine the risk of hospital admission for myocarditis or pericarditis in individuals aged 16 and older following COVID-19 vaccination. This analysis found an elevated risk within 28 days of the first dose of ChAdOx1-S and mRNA-1273 vaccines, as well as after the second dose for both mRNA vaccines. Subsequently, the study was updated to include data from the booster vaccination campaign, revealing an elevated risk within 28 days of a booster dose of the BNT162b2 vaccine. However, there was insufficient power to assess the risk by age and sex, as well as for the mRNA-1273 vaccine.

To better understand this issue, epidemiological studies were conducted in various countries to assess the risk associated with different COVID-19 vaccine platforms, including mRNA vaccines like BNT162b2 and mRNA-1273, as well as adenovirus-vectored vaccines such as ChAdOx1-S. In a new study published in the journal PloS Medicine, Professor Elizabeth Miller from the NIHR Health Protection Research Unit in Vaccines and Immunization at London School of Hygiene and Tropical Medicine, in collaboration with Dr. Julia Stowe, Dr.  Nick Andrews and Dr.  Heather J. Whitaker at UK Health Security Agency, conducted a study to estimate the risk of myocarditis or pericarditis after a booster dose of BNT162b2 or mRNA-1273 vaccines in England, taking into account age, sex, and the type of vaccine platform used for priming. The authors analyzed data from 3,124 hospital admissions and 7,933 emergency care consultations for myocarditis or pericarditis between February 22, 2021, and February 6, 2022

The study analysis showed higher background admission rates for myocarditis compared to pericarditis, with males having roughly double the admission rates of females. Admission rates also increased significantly with age, particularly among individuals aged 12 to 19 years. Additionally, certain ethnic groups and individuals with specific risk flags exhibited higher rates of admission. Regarding post-vaccination analyses, the study found an elevated risk of hospital admission for myocarditis within 0 to 6 days after receiving mRNA vaccines in individuals aged under 40 years. This risk was also observed after the first dose of the ChAdOx1-S vaccine. The highest risks were associated with the second dose of mRNA vaccines, with higher risks for the mRNA-1273 vaccine compared to the BNT162b2 vaccine. Elevated risks were higher in males than in females. Furthermore, individuals aged 16 to 24 years had a higher risk than those aged 25 to 39 years. Interestingly, there was less evidence of a vaccine-associated risk for pericarditis admissions, except for the 0 to 6 days after the second dose of the mRNA-1273 vaccine in individuals aged 16 to 39 years. Emergency care consultations for both pericarditis and myocarditis showed elevated risks in the same age group, consistent with the results from hospital admissions. When stratified by the vaccine used for priming, both mRNA vaccines exhibited an elevated risk when given as a booster after two doses of BNT162b2 vaccine in individuals aged 16 to 39 years. However, there was no significant risk increase when BNT162b2 or mRNA-1273 booster doses were given after a priming course of ChAdOx1-S vaccine.

The authors’ findings shed light on the risk of myocarditis and pericarditis following booster doses of mRNA COVID-19 vaccines in England. It confirms previous research showing an increased risk of hospital admission for myocarditis or pericarditis after receiving mRNA vaccines, particularly in males aged 16 to 39 years, with the highest risk in those aged 16 to 24 years. The study also indicates that the risk of myocarditis or pericarditis may be influenced by the mRNA dose administered, with higher risk associated with the mRNA-1273 vaccine. This suggests a potential dose-related innate immune activation as a contributing factor. While there has been speculation about an immune-mediated mechanism involving antibodies to components of the spike protein, the study’s findings do not support this hypothesis. The risk was not exacerbated in individuals with prior SARS-CoV-2 infection, nor was it increased after a booster dose, even though both scenarios would result in high levels of anti-spike IgG antibodies, particularly in younger adults. In contrast to the vaccine-associated risk, the researchers showed that the risk of myocarditis or pericarditis after a confirmed SARS-CoV-2 infection is greater in older adults and similar for both outcomes. This risk persists regardless of vaccination status and is evident for various variants of the virus.

The findings of Professor Elizabeth Miller and colleagues contribute to our understanding of vaccine safety and provide valuable information for public health decision-makers. As the COVID-19 pandemic continues to evolve, ongoing research and surveillance are essential to ensure the safety and effectiveness of vaccination strategies. It is crucial to balance the benefits of vaccination in preventing severe disease and death with the potential risks, and studies like this one play a vital role in informing these decisions. Ultimately, vaccination remains a critical tool in our fight against the SARS-CoV-2 virus, and its benefits continue to outweigh the associated risks for the vast majority of individuals.