Understanding Myocarditis, COVID-19 Infection, and COVID-19 Vaccines
November 1, 2024
EXECUTIVE SUMMARY
- Myocarditis is a rare, typically self-limited inflammatory condition of the heart often associated with pericarditis.
- Both infection with COVID-19 and messenger ribonucleic acid vaccination against COVID-19 are associated with the development of myocarditis.
- Manifestations include chest pain, shortness of breath, fever, and syncope. In more than half of patients, an electrocardiogram will show ST-segment elevation.
- Laboratory findings typically include an increase in troponin, C-reactive protein, and leukocytosis with eosinophilia.
- Brain natriuretic peptide (BNP) levels are almost always elevated and can remain elevated for up to three months and can be used to distinguish from acute coronary syndrome. In myocarditis, BNP typically is higher and troponin levels are significantly lower than in acute coronary syndrome.
- Determining if a vaccine is causal is difficult, but it is more likely if closely associated temporally to inoculation.
- The lowest incidence rate of post-vaccination myocarditis was in Singapore and the highest incidence rate was in Israel.
- Trends observed that the Moderna COVID-19 vaccine seemed to be more highly linked with myocarditis and the highest risk group in young males.
- Although there are no prospective data, it is recommended that exercise should be avoided for three to six months post-infection.
- Myocarditis is a rare condition that has been increasing in frequency even before the COVID-19 pandemic. The vast majority of cases are limited in time and severity.
- The risk of myocarditis with the COVID-19 vaccines is low, and much lower than the risk with COVID-19 infection itself.
- While sudden cardiac death has been speculated to be associated with vaccine-associated myocarditis, the current data do not support this.
- Because of changes in COVID-19 severity since the Omicron mutation and the progressive decline in vaccine efficacy, the decision to receive booster doses should be made on a case-by-case basis in consultation with a physician.
COVID-19 has evolved from a pandemic disease to an endemic condition, one that continuously circulates in the population with periods of increased and decreased incidence. In addition, the severity of COVID-19 infection has decreased with successive variants, as has vaccine efficacy. So why does the Centers for Disease Control and Prevention (CDC) recommend that everybody older than the age of 6 months be vaccinated with a 2024-2025 COVID-19 vaccine?
If you are like me, friends and family ask me if they should get vaccinated against COVID-19. I rarely get asked about other vaccines. I think some of the skepticism about the COVID-19 vaccine comes from the uncertainty surrounding our understanding of the disease and the vaccine during the early days of the pandemic. This uncertainty was amplified via social media, and purported adverse effects of the vaccine were highlighted. If an adverse vaccine reaction affected you, you were certain about that event, whereas if you had a mild illness with COVID-19, you might not be certain that was due to the vaccine. It is easier to be certain about an event that happened than one that did not.
One adverse effect of the COVID-19 infection and vaccination that garnered media attention is acute myocarditis and the risk of sudden death. This manuscript is written to inform you of the most recent data for these events. With this information, you can provide evidence-based recommendations to your friends, family, and patients.
— J. Stephan Stapczynski, MD, Editor
Introduction
Myocarditis is a rare, typically self-limited inflammatory condition of the heart. It often is associated with pericarditis.1 Although myocarditis is rare, interest has increased in recent years because of the COVID-19 pandemic and COVID-19 vaccinations both being associated with its development. Paralleling this interest is an increase in misinformation about this condition, its frequency associated with both COVID-19 infection and vaccination, and potential linkage to sudden cardiac death. This review article will trace the history of myocarditis from the pre-COVID-19 era to the present day, with special attention being paid to how social media has driven a large portion of the discussion.
Myocarditis: Past History, Pre-COVID-19
Myocarditis is extremely rare. Historical data put the incidence at 0.02% of the general population.2 Although COVID-19 and the COVID-19 vaccines have increased the interest in this uncommon condition, the incidence was climbing even before the pandemic. In a Chinese review looking at myocarditis rates from 1990-2019, there was a 62.1% increase in absolute case volume over that time period, but the relative case load standardized to population went down 4.4%. There also was a 65.4% increase in absolute deaths associated with myocarditis, but no real change when standardized to population over the same time (0.46% death rate in 1990 and 0.43% death rate in 2019).3
The increase in absolute cases of myocarditis likely is the result, in part, of novel cardiovascular magnetic resonance (CMR) methods that have increased the ability to diagnose this condition.4 A similar phenomenon has been observed in recent years regarding the incidence of childhood autism. According to the CDC, there has been a significant increase in the diagnosis rates of autism since 2000. The prevalence of autism in 2000 was 6.7 per 1,000 children. By 2020, the prevalence increased to 27.6 per 1,000 children. Factors driving this, like the increase in myocarditis diagnoses, involve better screening, an increase in awareness, and enhanced diagnosis.5
Currently, the incidence of myocarditis in the United States as the result of COVID-19 infection has been estimated by the CDC to be about 150 cases per 100,000 persons compared to nine cases per 100,000 persons as the result of a non-COVID-19 etiology throughout the same time period, corresponding to a greater than 15-fold increase in the risk of developing myocarditis because of a COVID-19 infection compared to non-COVID-19 etiologies.6
Evaluation and Treatment of Myocarditis
The manifestations of myocarditis include chest pain (the most common complaint), shortness of breath, fever, and syncope. History plays a critical role when considering this diagnosis, since many different conditions, substances (COVID-19 vaccines included), and exposures (COVID-19 or other viral illness) can contribute to its development.7
Pertinent medical history includes any recent respiratory infections, drugs, vaccines, raw meat consumption, family history of heart conditions, current conditions, and previous myocarditis. In more than half of patients, an electrocardiogram (ECG) will show ST-segment elevation, similar to an acute myocardial infarction.
Laboratory findings typically will include an increase in troponin and C-reactive protein. Leukocytosis with eosinophilia also can be seen.7 Serum brain natriuretic peptide (BNP) is nearly always elevated, and the degree of elevation generally correlates with the extent of ventricular wall abnormalities. Levels typically peak at 48 hours after presentation and can stay elevated for up to three months. These values can be used to distinguish myocarditis from acute coronary syndrome (ACS), since BNP values in myocarditis typically are higher than troponin levels, usually less than 10 ng/mL.8
Family history is implicated in the development of myocarditis, since certain gene variants are associated with the condition.9 Recent infections related to myocarditis include parasitic infections (such as from raw meat ingestion), Lyme disease, and dengue fever. Additionally, substance and biologic exposures can contribute to its development. This includes drugs such as amphetamines, immune checkpoint inhibitors, and clozapine. Biologics include the smallpox vaccine as well as the mRNA COVID-19 vaccine.
If an infectious cause is suspected, antibody levels for certain organisms (human immunodeficiency virus, Borrelia species, etc.) should be investigated. In a patient with recent or current respiratory symptoms, a nasopharyngeal swab for respiratory viruses should be done.
Often, an initial method of assessment includes an echocardiogram, although this can be normal in about 75% of patients. Findings suggestive of acute myocarditis include increased wall thickness, mild hypokinesia (often the inferior walls), diastolic dysfunction, pericardial effusion, and mild dilation of left ventricle. These findings are nonspecific, and cardiac magnetic resonance imaging (MRI) often is used to confirm the diagnosis via the visualization of edema and fibrosis.7 The gold standard for diagnosis is an endomyocardial biopsy, which, because of its invasive nature, is reserved for complicated cases.7
Treatment of myocarditis is based on whether the disease is considered complicated or uncomplicated, representing about 25% and 75% of cases of acute myocarditis, respectively. Uncomplicated myocarditis typically presents with acute chest pain and has no mechanical or electrical cardiac dysfunction. The mortality rate of uncomplicated acute myocarditis is nearly 0%, so treatment is generally symptomatic with nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Although NSAIDs do not significantly decrease inflammatory injury, they are indicated for pain.10 Angiotensin converting enzyme (ACE) inhibitors and beta-blockers are sometimes administered; however, there is weak evidence suggesting that beta-blockers may reduce morbidity and mortality.11,12
Complicated myocarditis may involve left ventricular systolic dysfunction, acute heart failure, atrioventricular conduction dysfunction, or arrhythmias. About 12% of patients with complicated acute myocarditis either die in the hospital or undergo a heart transplant.12 Depending on the types of complications, an antiarrhythmic drug, pacemaker, or defibrillation may be necessary. In other cases, an etiology must be identified to address and treat the underlying cause. In cases with heart failure and reduced ejection fraction, heart failure medications are indicated. If the myocarditis is severe, positive inotropes may be necessary.7
Timeline of Concern of COVID-19-Associated Myocarditis
COVID-19-associated myocarditis created a significant social media scare when Wayne J. Sebastianelli, MD, (the director of athletic medicine at Penn State University) misquoted preliminary data that were shared with him. He was quoted saying that 30% to 35% of all athletes who were infected with COVID-19 developed myocarditis proven by MRI findings. Within four days, an official correction was issued, but the concern level already was raised.13
The actual data showed that, of 9,255 Big 10 athletes tested for COVID-19, 30.4% experienced seroconversion rather than developed myocarditis. Of those, only 2.3% had MRI-proven myocarditis and only 0.3% (nine individuals) had any clinical symptoms. There were no deaths reported in this group.14
Vaccine-Associated Myocarditis
Determining if a vaccine is causal in a case of myocarditis is difficult but thought likely if closely temporally related to inoculation. A large review gathered reports of COVID-19 vaccine-associated myocarditis from around the world.15 The lowest experience was in Singapore, which had an incidence rate of only 0.1 to 1.0 cases per 100,000 persons.6 The highest rate was in Israel at 11 cases per 100,000 persons.16
In an analysis of the Vaccine Adverse Event Reporting System (VAERS) database, the self-reported incidence of presumed COVID-19 vaccine-induced myocarditis was 0.38 per 100,000 persons. In the same analysis, the relative risk of self-reported myocarditis from an mRNA COVID-19 vaccine was 88% less than that seen from the smallpox vaccine, which is well-established to cause myocarditis.15
Several trends also were noted. The Moderna COVID-19 vaccine seemed to be more highly linked to cases of myocarditis than the Pfizer/BNT agent. The worldwide experience with the Moderna vaccine was associated with 9.2 cases per 100,000 persons.17 The other pattern that developed was that young males seemed to have a higher predilection to myocarditis regardless of the vaccine received. Young males in Israel had an incidence rate up to 10.7 cases per 100,000 persons.18 The highest risk group was young males who received the Moderna product, with an incidence rate of up to 53.8 cases per 100,000 persons.17 This makes sense, since the Moderna vaccine contains roughly three times the mRNA as the Pfizer/BNT product.19
Although all therapeutic medications will have a risk-benefit ratio, these reports raised the level of concern for a widespread vaccination program that included young males. This was tempered by the fact that most cases of vaccine-associated myocarditis were mild and self-limited. The comparative ratio to consider in the decision to receive a vaccine is that the rate of myocarditis is 15 times higher with COVID-19 infection than from vaccination.6 (See Table 1.)
Table 1. Risk of Myocarditis with Highest Vaccine Reported Rates6,15,17,18 |
||
Absolute Risk |
Relative Risk |
|
General population |
9 per 100,000 persons |
Baseline risk = 1 |
Any vaccine |
0.38 per 100,000 persons |
< 1 |
Pfizer/BNT COVID-19 vaccine |
2.13 per 100,000 persons |
< 1 |
Smallpox vaccine |
4.56 per 100,000 persons |
< 1 |
Moderna COVID-19 vaccine |
9.2 per 100,000 persons |
~ 1 |
Pfizer/BNT COVID-19 vaccine (young males) |
10.7 per 100,000 persons |
~ 1 |
Moderna COVID-19 vaccine (young males) |
53.8 per 100,000 persons |
~ 5-fold17 |
COVID-19 infection |
150 per 100,000 persons |
> 15-fold6 |
Beyond myocarditis, a study using electronic health record data from 40 healthcare systems compared the incidence of cardiac outcomes (myocarditis, pericarditis, multisystem inflammatory syndrome, or a combination) after infection by SARS-CoV-2 to post-vaccination. For males between the ages of 12-17 years, data showed that the highest incidence of cardiac events occurred within 21 days after SARS-CoV-2 infection, with incidences reaching 24.7 per 100,000 persons for myocarditis and 93.3 per 100,000 persons for myocarditis, pericarditis, or multisystem inflammatory syndrome.
In comparison, the incidence of myocarditis within 21 days of the second dose of the mRNA COVID-19 vaccine was significantly lower, at 1.0 per 100,000 persons. Within this same demographic, the risk for cardiac outcomes was 1.8 to 5.6 times higher after SARS-CoV-2 infection compared to post-vaccination. Similar findings of a significantly increased risk after infection compared to after the vaccine were seen in other sex/age groups, with risk ratios ranging from 2.2 to 115.2.20
In a study of individuals hospitalized for myocarditis after SARS-CoV-2 vaccination in England from Dec. 1, 2020, to Dec. 15, 2021, the highest number of myocarditis cases were observed after the first dose of the ChAdOx1 vaccine (2,244 cases), followed by the first dose of the BNT162b2 vaccine (124 cases), and the second dose of the mRNA-1273 vaccine (40 cases). The incidence rate ratio (IRR) for myocarditis was 2.64 (95% confidence interval [CI], 1.25 to 5.58) after the first dose of mRNA-1273, 11.76 (95% CI, 7.25 to 19.08) after the second dose, and 2.64 (95% CI, 1.25 to 5.58) after the booster dose.
For comparison, the IRR was 11.14 (95% CI, 8.64 to 14.36) after a positive SARS-CoV-2 test before vaccination and 5.97 (95% CI, 4.54 to 7.87) after a positive SARS-CoV-2 test post-vaccination. These findings indicate that although the risk of myocarditis is elevated after both SARS-CoV-2 infection and mRNA vaccination, there is a protective benefit of vaccination in preventing severe COVID-19 outcomes that may outweigh these risks, especially considering the higher incidence of myocarditis following infection.21
There are five other very large-scale observational studies of the post-vaccination period that help us understand the risk.18,22-25 The first study from the United States — Oster et al — looked not at patients, but at doses given.22 They tracked 354,100,845 doses and found there were only 1,626 cases of myocarditis reported, for an incidence rate of 0.0009% per dose. This study also found that younger males were more likely to develop myocarditis, while the event rate in women was lower and did not change much based on age. The limiting factor in this study is that the researchers only tracked cases up to seven days after receiving a vaccine dose. Although this makes the strength of association stronger because of a tighter temporal relationship, there could be missed cases.22
The second and probably most well-known study from Israel — Witberg et al — is an analysis of the Clalit Health Services, which had 2.5 million vaccinated individuals.18 The overall incidence of myocarditis was 2.13 cases per 100,000 persons. The highest risk group was young males aged 16-29 years, with a rate of 10.69 per 100,000 persons.18
The third study from four Nordic countries, Denmark, Finland, Norway, and Sweden — Hviid et al — looked only at booster doses but focused on young subjects (both genders, aged 12-39 years).23 This was a very large study of 8,859,339 people. This study reproduced the earlier findings that the vaccines were associated with myocarditis, that there were more cases post-Moderna booster vaccination, and that males were more affected than females. The risk ratio for myocarditis in young males after receiving the Pfizer/BNT vaccine was 2.08, while the risk ratio for the Moderna product was 8.89. Young women also had a higher risk ratio of 3.99 with the Pfizer/BNT vaccine, but with large CIs (0.41 to 38.64). There were not enough cases associated with the Moderna vaccine in women to report. When put into cases per 100,000 persons, the Pfizer/BNT vaccine was associated with 0.86 cases in men and 0.15 cases in females, while the Moderna vaccine was associated with an incidence of 1.95 per 100,000 young men. There were no deaths reported within 30 days of any of the vaccine-related cases of myocarditis.23
The fourth study, from the United Kingdom, Spain, and Estonia — Mercadé-Besora et al — followed more than 20 million patients for up to one year.24 Vaccination was associated with significant reductions in deep vein thrombosis, pulmonary embolism, arterial thrombosis or embolism, stroke, myocardial infarction, and heart failure in vaccinated patients who incurred COVID-19 infection. These results also appeared to be durable over time.24
Within the first 30 days of infection, vaccination provided a significant reduction in the incidence of myocarditis and pericarditis. However, this protection did not last, and there was a non-significant trend for increased myocarditis and pericarditis over time. Furthermore, there also was early protection against ventricular arrhythmia or cardiac arrest that also seemed to wane over time. Finally, there was early protection against hemorrhagic stroke that also did not persist over time. All these CIs were extremely wide, and the point estimates all remained on the positive side of the line of unity.24
The final study from England — Ip et al — is the largest.25 This study of more than 45.7 million adults in England looked at various vaccines, initial doses and boosters, and multiple adverse events. As demonstrated in the other studies, there was an increase in cases of myocarditis and pericarditis after vaccination that peaked about two weeks after an inoculation. The incidence returned to normal after four weeks for both conditions.25
Sudden Cardiac Death
A major rallying point for people who are against taking the vaccines and frank “anti-vaxxers” is the risk of sudden cardiac death (SCD). Occasionally, when a health event occurs shortly after vaccination, it often is incorrectly attributed to the vaccine. A notable example is 26-year-old football player Damar Hamlin, who collapsed during a football game in 2023 because of cardiac arrest. He was resuscitated on the field and eventually recovered. After Hamlin’s collapse, there were comments suggesting it possibly was vaccine-related.26 However, it was concluded that his cardiac arrest was caused by a blow to the chest, a classic case of commotio cordis.27 According to the director of the Precision Vaccines Program at Boston Children’s Hospital, no vaccine has ever been proven to be linked to SCD.26
Association does not prove causation. An example of this is sudden infant death syndrome (SIDS). One common vaccine-related myth is that the vaccines (specifically the diphtheria-tetanus-pertussis [DTP] vaccine) can cause SIDS. This misconception arises because many children who die of SIDS recently had received the DTP vaccine, suggesting a causal link. However, most SIDS cases occur during the age at which DTP shots are administered, so this association is expected by chance. Well-controlled studies from the 1980s found no causal relationship between the DTP vaccine and SIDS, with some studies indicating a lower risk of SIDS in vaccinated children. The Institute of Medicine concluded that there is no evidence of a causal link between the DTP vaccine and SIDS.28
We are living in a post-truth, post-modern age. The director-general of the World Health Organization (WHO) refers to the degree of easily shareable, low-quality data as an “infodemic” or misinformation epidemic.10 In a study of more than 112 million social media posts, 40% had unreliable sources and 42% were generated by bots.7 Another study demonstrated that 50.5% of the fake stories regarding COVID-19 were spread via social media, totaling more than 4.5 billion views in a single month.13,14
One of the most well-known sources of this fear is the movie “Died Suddenly.”29 As of the writing of this review, it has been viewed more than 10 million times on Rumble and more than 1.7 million times on X (formerly Twitter), and it is available on other media platforms such as YouTube. It has been speculated that more than 15 million people have seen it.30 Readers are referred to two outside critical reviews of the movie by McGill University (https://www.mcgill.ca/oss/arti...) and by the BBC (https://www.bbc.com/news/healt...).
As mentioned earlier, even tight temporal correlation does not prove causation. To better understand this, here is a gedankenexperiment — German for “thought experiment” — popularized by Albert Einstein to help us see how easy it is to be swayed by our own biases.
Cardiovascular (CV) disease is the No. 1 cause of death in the United States.31 SCD itself makes up the largest proportion of CV deaths.32 SCD typically is a clinical diagnosis, since autopsies are rare. So, deaths that are attributed to SCD possibly are misassigned. Other diagnoses that could lead to sudden death include massive pulmonary embolus, internal bleeding, ruptured aortic aneurysm, intracranial hemorrhage, sepsis, and choking.
Consider the fictional case study of Jane Doe. Jane has known heart disease. She walked into a meeting at work and dropped dead. Most will think she had a massive myocardial infarction or had a small myocardial infarction with ventricular fibrillation, leading to sudden death.
Repeat the same scenario, but this time factor in that Jane got the COVID-19 vaccine two days ago. What caused her death? We still do not know for sure, but many will suspect the vaccine.
Suppose we repeat the two scenarios discussed earlier, but in both cases an autopsy was performed. The autopsy showed a fresh, acute myocardial infarction. In the scenario without the vaccine, we would say that she had a secondary cardiac event that led to SCD.
Now, rethink the second example with Jane getting the vaccine two days before, but with the same autopsy results. What would you say? Would it be the same explanation noted earlier or should we attribute it to the vaccine?
Young people do die suddenly. In a large review of deaths in individuals younger than 25 years of age, there were several categories that easily could be classified as SCD. The sixth leading cause (after accidents, homicides, suicides, cancer, and major CV disease) was drowning. This is interesting, since there are new autopsy data showing a higher-than-expected prevalence of mutations for various long QT syndromes in drowning victims that should reclassify them to SCD.33
Not only do young people die suddenly, but healthy ones do as well. In the same article, the annual absolute death toll for any athlete in the United States who is younger than 25 years of age was 120 total deaths. For any National Collegiate Athletics Association (NCAA) athlete, it was 18. To put this into perspective, only 25 persons younger than 25 years of age died from lightning strikes. Although it is rare for a young person to die, it does happen.33
What is the event rate in healthy and relatively young people? In a nationwide study in Denmark looking at SCD in competitive and non-competitive athletes aged 12 to 49 years, the rate was 0.43 per 100,000 persons in non-competitive athletes vs. 0.47 per 100,000 persons in competitive athletes. For comparison, the SCD rate in the general population was 10.7 per 100,000 persons.34
Probably the best-known study of SCD in athletics is the RACER study of marathon and half-marathon participants. This was a 10-year study of more than 10.9 million marathon and half-marathon runners. There were 59 cardiac events with a 71% fatality rate. The vast majority of the events occurred in the last quarter of either event. More importantly, 52% of the cases had known or possible cardiomyopathy, while 7% had known ventricular tachycardia. The event rates were 1.01 per 100,000 persons for the marathon and 0.67 per 100,000 persons for the half marathon. Once again, although this is a rare event in healthy individuals, it does happen.35
It is worth noting that while there is a finite risk with anything, including exercise, regular exercise was associated with a significant survival advantage. In the Denmark study cited earlier, the rate of SCD in the general population was 10.7 per 100,000 persons compared to 0.47 per 100,000 persons in the non-competitive athlete group.34 To further highlight the safety of exercise by contrasting it with other activities, there are an average of more than 17,000 emergency department visits as the result of injuries directly related to television sets.36
At present, there is only a single study looking at SCD related to vaccination. This study from Oregon strictly looked at adolescents and young adults from 2021-2022. The baseline death rate in Oregon was 4.1 per 100,000 persons in 2021. There were 1,292 deaths in the studied age group in 2021-2022. A total of 979,289 doses of COVID-19 vaccine were given over that same time period. Only one death was reported within 100 days of injection. Over same time period, there were 30 deaths from COVID-19 infection.37
Return to Work and Sports Post-Myocarditis
There are no prospective data on when it is safe to return to exercise post-myocarditis. It is recommended that if a patient is diagnosed with myocarditis, exercise should be avoided for three to six months because of the finding that exercise can increase the risk of SCD in myocarditis. To be safely cleared for activity, repeat screenings, including a resting echocardiogram, a 24-hour Holter monitor, and an exercise ECG, are needed.38
One recent guideline specifically looking at post-COVID-19 infections uses symptoms, time from infection, infection severity, and diagnostic testing to help recommend return to play (RTP) in elite athletes.39 They recommend RTP after at least seven days of symptom-free rest. They also recognize that these guidelines should be reviewed as more data become available. For a more complete discussion of RTP post-COVID-19, the reader is referred to the ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults.40
Although there is a concern with exercise and RTP acutely after an episode of myocarditis, there is strong evidence for the benefits of exercise early in the course of other serious cardiac conditions.
Evidence suggests that early mobilization after a myocardial infarction can help decrease inflammation and the extent of negative cardiac remodeling. According to the American Heart Association guidelines, a patient with an ST-elevation myocardial infarction (STEMI) without complications (such as ischemia, heart failure, or arrhythmia) should not be bedridden for more than 12 to 24 hours after the start of symptoms. There is a scarce amount of current data regarding the timing of mobilization post-myocardial infarction, but the limited older data suggest early mobilization is associated with a 15% reduction of mortality risk.
Exercise has been shown to have beneficial effects in the setting of inflammation, with manifestations including a decrease in levels of inflammatory biomarkers such as C-reactive protein, interleukins, and tumor necrosis factor alpha. A study on patients with heart failure showed that the implementation of 30 minutes of exercise five days per week for six weeks was associated with significantly reduced levels of tumor necrosis factor alpha and significantly increased functional capacity.41 See Table 2 for the relative risks of groups who exercise compared to the baseline general population.
Table 2. Sudden Cardiac Death Rates34,35 |
|
Group |
Sudden Cardiac Death Rate |
General population |
10.7 per 100,000 persons |
Young non-competitive athletes |
0.43 per 100,000 persons |
Young competitive athletes |
0.47 per 100,000 persons |
Half-marathon participants, all ages |
0.67 per 100,000 persons |
Full marathon participants, all ages |
1.01 per 100,000 persons |
COVID Calculus: What Is the Current Risk-Benefit Ratio for Taking Additional Boosters?
The final question we will address is how do the current data on myocarditis risk affect the shared decision-making discussion about obtaining future COVID-19 boosters? In medicine, we typically think and talk in proportions or risk ratios, specifically the risk-benefit ratio. Beyond the finite risks of myocarditis, there are two other moving targets that factor heavily into this discussion.
The most important one is the nature of the COVID-19 virus itself. The initial wave and the Delta wave had significant morbidity and mortality. Virulence dropped sharply with the Omicron mutation. The latest case fatality ratio now is well below 1% and is at 0.3% worldwide. In fact, the lethality of the virus has dropped by 96.8% over the past 2.5 years. This is excellent news.42
The other factor that is almost as important is vaccine efficacy. The initial studies of the Pfizer/BNT vaccine demonstrated a 95% reduction in infection rate and the Moderna vaccine demonstrated a similar 94% reduction.43 These same mRNA vaccines had significantly less effect on the Omicron variant and only led to a 66% reduction in infection rate.44 The most recent analysis shows that the current boosters only result in a 54% reduction in infection as of January 2024.45 See Table 3 for a parallel account of both factors over time.
Table 3. COVID Severity and Vaccine Efficacy over the Course of the Pandemic42-45 |
||
Case Fatality Rate |
Vaccine Efficacy |
|
Initial wave |
8.5% |
95% |
Omicron variant |
0.7% |
66% |
Most recent data |
0.27% |
54% |
Another study looked at the effect of vaccines not on myocarditis but on post-acute sequelae of SARS-CoV-2 (PASC), otherwise known as long COVID. In this large (more than 5 million veterans), observational study, there was a significant and stepwise reduction in the cases of long COVID as measured from the pre-Delta period to the Delta period and, finally, in the Omicron time period. Vaccination was associated with a further reduction in cases of long COVID. Of the total decrease in long COVID cases, waning virus virulence was thought to contribute 28%, while vaccination contributed 72% of the seen reduction.46
Age is an important factor associated with COVID-19 infection severity, and the case-fatality especially increases in those older than 70 years of age, as displayed in Table 4.
Table 4. Approximate Case-Fatality for COVID-19 Infection According to Age |
||
Age Range |
Case-Fatality Rate |
Case-Fatality Rate per 100,000 cases |
0-4 y |
0.003% |
3 |
5-9 y |
0.0008% |
1 |
10-14 y |
0.001% |
2 |
15-19 y |
0.003% |
3 |
20-24 y |
0.01% |
10 |
25-29 y |
0.02% |
20 |
30-34 y |
0.03% |
30 |
35-39 y |
0.03% |
30 |
40-44 y |
0.08% |
80 |
45-49 y |
0.1% |
100 |
50-54 y |
0.2% |
200 |
55-59 y |
0.3% |
300 |
60-64 y |
0.5% |
500 |
65-69 y |
1% |
1,000 |
70-74 y |
2% |
2,000 |
75-79 y |
3% |
3,000 |
80+ y |
8% |
8,000 |
Adapted from: O’Driscoll M, Ribeiro Dos Santos G, Wang L, et al. Age-specific mortality and immunity patterns of SARS-CoV-2. Nature 2021;590:140-145. |
||
A rational, logical decision to either obtain a COVID-19 vaccine booster or to refrain from vaccination should be based on personal risk of severe infection or death, potential complications of seroconversion to COVID-19, effectiveness of the vaccine, and the risk profile side effects of the vaccine itself.
Summary
Both COVID-19 infection and COVID-19 vaccinations have been associated with the development of myocarditis. The risk from COVID-19 infection is more than 15-fold that of the vaccine. Vaccine-associated myocarditis appears to be mild and self-limited, with a predilection for young males. SCD is the most common cause of death in the United States and, although rare in young and healthy persons, it still does occur. At present, there does not seem to be an association between the COVID-19 vaccines and SCD. Shared decision-making about obtaining further booster doses should include a discussion of the risk-benefit ratio, taking into account age, gender, and the waning virulence of the virus itself, as well as the reduced efficacy of the vaccines.
Serena Fadell, MS-3, is a medical student at Wright State University Boonshoft School of Medicine, Dayton, OH. Harvey S. Hahn, MD, is Program Director, Cardiovascular Fellowship Training Program, Kettering Medical Center, Kettering, OH.
References
- Sexson Tejtel SK, Munoz FM, Al-Ammouri I, et al. Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2022;40:1499-1511.
- Kang M, Chippa V, An J. Viral Myocarditis. StatPearls [Internet]. StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK459259/
- Wang YWY, Liu RB, Huang CY, et al. Global, regional, and national burdens of myocarditis, 1990–2019: Systematic analysis from GBD 2019: GBD for myocarditis. BMC Public Health 2023;23:714.
- Ferrieira VM, Piechnik SK, Dall’Armellina E, et al. Abstract 17917: Novel techniques for the diagnosis of acute myocarditis: A clinical cardiovascular magnetic resonance study. Circulation 2023;126(suppl_21). https://www.ahajournals.org/doi/abs/10.1161/circ.126.suppl_21.A17917
- Richter F. The rising prevalence of autism. Chart: The rising prevalence of autism: Identified prevalence of autism spectrum disorder (ASD) per 1,000 children in the U.S. Statista. Published April 2, 2024. https://www.statista.com/chart/29630/identified-prevalence-of-autism-spectrum-disorder-in-the-us/
- Fairweather DL, Beetler DJ, Di Florio DN, et al. COVID-19, myocarditis and pericarditis. Circ Res 2023;132:1302-1319.
- Ammirati E, Moslehi JJ. Diagnosis and treatment of acute myocarditis: A review. JAMA 2023;329:1098-1113.
- Medina de Chazal H, Del Buono MG, Keyser-Marcus L, et al. Stress cardiomyopathy diagnosis and treatment: JACC state-of-the-art review. J Am Coll Cardiol 2018;72:1955-1971.
- Ammirati E, Raimondi F, Piriou N, et al. Acute myocarditis associated with desmosomal gene variants. JACC Heart Fail 2022;10:714-727.
- Berg J, Lovrinovic M, Baltensperger N, et al. Non-steroidal anti-inflammatory drug use in acute myopericarditis: 12-month clinical follow-up. Open Heart 2019;6:e000990.
- Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation 2008;118:639-648.
- Ammirati E, Figerio M, Adler ED, et al. Management of acute myocarditis and chronic inflammatory cardiomyopathy. An expert consensus document. Circ Heart Fail 2020;13:e007405.
- Asmelash L, De la Fuente H. Penn State clarifies doctor’s comments on Covid-19 and myocarditis. CNN. Published Sept. 4, 2020. https://www.cnn.com/2020/09/03/health/penn-state-big-10-myocarditis-covid-spt-trnd/index.html
- Daniels CJ, Rajpal S, Greenshields JT, et al. Prevalence of clinical and subclinical myocarditis in competitive athletes with recent SARS-CoV-2 infection: Results from the Big Ten COVID-19 Cardiac Registry. JAMA Cardiol 2021;6:1078-1087.
- Rafaniello C, Gaio M, Zinzi A, et al. Disentangling a thorny issue: Myocarditis and pericarditis post COVID-19 and following mRNA COVID-19 vaccines. Pharmaceuticals (Basel) 2022;15:525.
- Barda N, Dagan N, Ben-Shlomo Y, et al. Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting. N Engl J Med 2021;385:1078-1090.
- Straus W, Urdaneta V, Esposito DB, et al. Analysis of myocarditis among 252 million mRNA-1273 recipients worldwide. Clin Infect Dis 2023;76:e544-e552.
- Witberg G, Barda N, Hoss S, et al. Myocarditis after Covid-19 vaccination in a large health care organization. N Engl J Med 2021;385:2132-2139.
- Richards NE, Keshavarz B, Workman LJ, et al. Comparison of SARS-CoV-2 antibody response by age among recipients of the BNT162b2 vs the mRNA-1273 vaccine. JAMA Netw Open 2021;4:e2124331.
- Block JP, Boehmer TK, Forrest CB, et al. Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination — PCORnet, United States, January 2021-January 2022. MMWR Morb Mortal Wkly Rep 2022;71:517-523.
- Patone M, Mei XW, Handunnetthi L, et al. Risk of myocarditis after sequential doses of COVID-19 vaccine and SARS-CoV-2 infection by age and sex. Circulation 2022;146:743-754.
- Oster ME, Shay DK, Su JR, et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA 2022;327:331-340.
- Hviid A, Nieminen TA, Pihlström N, et al. Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: A Nordic cohort study. Eur Heart J 2024;45:1327-1335.
- Mercadé-Besora N, Li X, Kolde R, et al. The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications. Heart 2024;110:635-643.
- Ip S, North TL, Torabi F, et al. Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million adults in England. Nat Commun 2024;15:6085.
- Lovelace B Jr. Covid vaccines not linked to fatal heart problems in young people, CDC finds. NBC News. Published April 11, 2024. https://www.nbcnews.com/health/health-news/cdc-finds-covid-vaccines-not-linked-sudden-death-young-people-rcna147188
- Link MS, Estes NAM 3rd, Maron BJ; American Heart Association Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and American College of Cardiology. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 13: Commotio cordis: A scientific statement from the American Heart Association and American College of Cardiology. Circulation 2015;132:e339-342.
- World Health Organization. Vaccines and immunization: Myths and misconceptions. Published Oct. 19, 2020. https://www.who.int/news-room/questions-and-answers/item/vaccines-and-immunization-myths-and-misconceptions
- Rumble. Died Suddenly 2022 (Full Documentary). https://rumble.com/v1wcs7o-died-suddenly-2022-full-documentary.html?gad_source=1&gclid=EAIaIQobChMIy_f6q-HZhgMVH09HAR3HXQgGEAAYASAAEgJb9_D_BwE
- Rumble. Died Suddenly goes mega viral documentary tops 10 million+ views, sparks Congressional hearing. https://rumble.com/v1xqoj2-died-suddenly-goes-mega-viral-documentary-tops-10-million-views-sparks-cong.html
- Centers for Disease Control and Prevention. Multiple cause of death data. National Center for Health Statistics. Mortality Data on CDC WONDER. Last reviewed April 26, 2024. https://wonder.cdc.gov/mcd.html
- Sudden Cardiac Arrest Foundation. AHA releases latest statistics on sudden cardiac arrest. Published Feb. 1, 2018. https://www.sca-aware.org/sca-news/aha-releases-latest-statistics-on-sudden-cardiac-arrest
- Maron BJ, Friedman RA, Kligfield P, et al. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age): A scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 2014;64:1479-1514.
- Risgaard B, Winkel BG, Jabbari R, et al. Sports-related sudden cardiac death in a competitive and a noncompetitive athlete population aged 12 to 49 years: Data from an unselected nationwide study in Denmark. Heart Rhythm 2014;11:1673-1681.
- Kim JH, Malhotra R, Chiampas G, et al. Cardiac arrest during long-distance running races. N Engl J Med 2012;366:130-140.
- ABC News. Falling televisions send a child to emergency room every 30 minutes, study finds. Published July 22, 2013. https://abcnews.go.com/US/falling-televisions-send-child-emergency-room-30-minutes/story?id=19736761
- Liko J, Cieslak PR. Assessment of risk for sudden cardiac death among adolescents and young adults after receipt of COVID-19 vaccine — Oregon, June 2021-December 2022. MMWR Morb Mortal Wkly Rep 2024;73:317-320.
- Bryde RE, Cooper LT Jr, Fairweather DL, et al. Exercise after acute myocarditis: When and how to return to sports. Cardiol Clin 2023;41:107-115.
- Wilson MG, Hull JH, Rogers J, et al. Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: A practical guide for sport and exercise medicine physicians. Br J Sports Med 2020;54:1157-1161.
- Writing Committee; Gluckman TJ, Bhave NM, Allen LA, et al. 2022 ACC expert consensus decision pathway on cardiovascular sequelae of COVID-19 in adults: Myocarditis and other myocardial involvement, post-acute sequelae of SARS-CoV-2 infection, and return to play: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2022;79:1717-1756.
- Meng Y, Zhuge W, Huang H, et al. The effects of early exercise on cardiac rehabilitation-related outcome in acute heart failure patients: A systematic review and meta-analysis. Int J Nurs Stud 2022;130:104237.
- Horita N, Fukumoto T. Global case fatality rate from COVID-19 has decreased by 96.8% during 2.5 years of the pandemic. J Med Virol 2023;95:e28231.
- Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.
- Link-Gelles R, Levy ME, Natarajan K, et al. Estimation of COVID-19 mRNA vaccine effectiveness and COVID-19 illness and severity by vaccination status during Omicron BA.4 and BA.5 sublineage periods. JAMA Netw Open 2023;6:e232598.
- Link-Gelles R, Ciesla AA, Mak J, et al. Early estimates of updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection attributable to co-circulating Omicron variants among immunocompetent adults — increasing community access to testing program, United States, September 2023-January 2024. MMWR Morb Mortal Wkly Rep 2024;73:77-83.
- Xie Y, Choi T, Al-Aly Z. Postacute sequelae of SARS-CoV-2 infection in the pre-Delta, Delta, and Omicron eras. N Engl J Med 2024;391:515-525.
Although myocarditis is rare, interest has increased in recent years because of the COVID-19 pandemic and COVID-19 vaccinations both being associated with its development. This review article will trace the history of myocarditis from the pre-COVID-19 era to the present day.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content
Already have an account? Log in