Yes, the mRNA vaccine (especially Moderna’s) increases the risk of myocarditis substantially in young men, but not cardiac death.
I was appalled when I first read the news about the analysis published by the Florida Department of Health earlier this month, finding a staggering 84% increased risk of cardiac-related death among 18–39-year-old males within 28 days of getting the Covid-19 mRNA vaccine.
As a result, the Department and State Surgeon General now advise against using mRNA vaccines in this population. But is this advice sound? What’s with all the controversy between mRNA vaccine and the heart? And, in the end, is the benefit-risk ratio of mRNA vaccine in young men justified?
The Florida analysis is highly flawed
Earlier this month, the Florida Department of Health released an unpublished analysis — i.e., not formally published in a peer-reviewed scientific journal. The authors, unnamed, analyzed the dataset of Florida residents (≥18 years) who died within 25 weeks of getting the Covid-19 vaccine since the vaccine roll-out in December 2020.
Results revealed that at 28 days post-vaccination:
- No increased risk was found for all-cause deaths. But for those ≥60 years, a small 3% decreased risk of all-cause death was noted.
- 11% increased risk of cardiac-related deaths in males who received the mRNA vaccine. When stratified by age groups, males aged 18–39 had the highest risk at 84% higher risk.
- 25% decreased risk of cardiac-related deaths in males who received vaccines other than the mRNA vaccine.
“With a high level of global immunity to COVID-19, the benefit of vaccination is likely outweighed by this abnormally high risk of cardiac-related death among men in this age group,” the Florida Department of Health announced. “The State Surgeon General now recommends against the COVID-19 mRNA vaccines for males ages 18–39 years old.”
For one, the authors used a self-control case series analysis where participants served as their own controls. Such analysis is useful for studying vaccine safety as it eliminates potential confounders such as health status, environmental influences, and genetics. In this analysis, person A is compared to person A at different time periods.
But the Florida analysis is flawed as it violated the analysis’s requirement that the endpoint measured in the first period should not affect the same in the second period. Death is, thus, not suitable to be studied in this manner, because person A who died in period 1 cannot die again in period 2.
To overcome this problem, person A who died in period 1 must be excluded from the denominator in period 2. But the Florida analysis did not perform this, leading to underestimated death risk in period 2 (i.e., the control period) and overestimated death risk in period 1.
Second, only 20 deaths occurred in the 18–39-year-old men who received the mRNA vaccine during the risk period (i.e., 28 days post-vaccination). This sample size is very small that if even a few of those deaths have another cause, the risk would no longer be statistically significant. And cohort studies like this can only tell us about association, not causation.
Third, cardiac-related death is a vague term. It only tells us that the death is possibly a cardiac one. The Florida paper admits that “This study cannot determine the causative nature of a participant’s death. We used death certificate data and not medical records.”
So, some of the cardiac-related deaths may have another obvious cause of death, such as bacterial pericarditis, which should be excluded from the analysis. And due to the small sample size, excluding such cases will likely render the results non-significant and the conclusion invalid.
Although the Florida State General Surgeon tweeted a rebuttal of the criticisms raised, the rebuttal isn’t adequate and appears misleading, as explained here by Kristen Panthagani, MD, PhD, an emergency medicine resident at Yale New Haven Hospital and science communicator.
What other more reliable studies show
The Florida paper based its analysis on previous work it cited, notably the preprint of Nafilyan et al. (2022) from the U.K. Office for National Statistics.
Nafilyan et al. also examined all cases of all-cause and cardiac-related deaths occurring in young people (aged 12–29) from England since vaccine roll-out using a self-controlled case series design, but a properly executed one without the major flaws found in the Florida paper.
Results revealed that at 6 weeks post-vaccination, no increased risk of all-cause or cardiac-related deaths was found, even after stratifying by age group, sex, vaccine type, and the number of doses.
A 50% decreased risk of all-cause death was noted at one-week post-vaccination. But the authors attributed this finding to the healthy vaccine effect. Ill people are more likely to delay vaccination until they have recovered, which probably led to higher medical complications (including death) in the unvaccinated period — an unbiased interpretation of the results, as accurate science should be.
Nafilyan et al. also analyzed the same for SARS-CoV-2-infected individuals, finding a whopping 500% and 340% increased risk of cardiac-related and all-cause mortality at 6 weeks post-infection.
Another nationwide study from Denmark (Husby et al.) also examined the risks of cardiac-related death from mRNA vaccines — finding a 50–60% reduced risk of cardiac arrest or death among participants who got the mRNA vaccine vs. the unvaccinated group at 28-day follow-up.
But the authors, again, believed this finding is a result of the healthy vaccine effect, stating that “the fact that SARS-CoV-2 vaccines are rarely given to people with an acute or terminal illness is a likely explanation for the low 28-day risk of cardiac arrest or death in our study.”
Like Nafilyan et al., Husby et al. also interpreted their findings fairly and justly, without using them to push an agenda such as Covid-19 vaccines being the holy grail of longevity or cardiac death prevention.
More concerningly, Husby et al. also found a 1300% increased risk of cardiac arrest or death among participants infected with SARS-CoV-2 compared to the uninfected group at 28-day follow-up — consistent with the findings of Nafilyan et al. and others.
Overall, the mRNA vaccine is not associated with cardiac-related deaths. If anything, such risk is several folds (6–14-fold or 500–1300%) higher from SARS-CoV-2 infection or Covid-19.
Anti-vaccine activists who tell you not to take Covid-19 vaccines to keep your heart pumping are, in fact, doing the very opposite.
But why are we focusing so much on cardiac issues from mRNA vaccines? And what does its benefit-risk ratio looks like now for young males?
The reason why everyone is so fixated on the risk of cardiovascular adverse events from the mRNA vaccine is due to myocarditis, now acknowledged as a known risk of mRNA vaccines.
In a semi-systematic review published a few months ago, I scoured the literature for all the adverse events — over 70 of them ranging from cardiovascular, neurological, thrombotic, and other adverse events — that may be associated with the mRNA vaccine. And only myocarditis appeared consistently associated with the mRNA vaccine.
However, myocarditis has gotten a bad rap as it’s one of the major causes of sudden death in young people. So, it’s unsurprising that mRNA vaccines have been blamed, rather unfairly, for cardiac-related deaths, especially among the anti-vaccine community.
Even the Florida State General Surgeon tweeted, “is it really that hard to imagine that mRNA COVID-19 vaccines that increase myocarditis in young men by 10x, 20x, or 30x (see Karlstad et al, JAMA Cardiology, 2022) also increase the risk of cardiac death in that age group?”
Currently, we have two types of mRNA vaccines against Covid-19 — BNT162b2 from Pfizer-BioNTech and mRNA-1273 from Moderna. These two mRNA vaccines are mostly similar, but the dose of Moderna’s mRNA vaccine is >3-times the dose of Pfizer’s, making Moderna’s mRNA vaccine more durable against Covid-19 yet more immunogenic.
In one of the largest vaccine safety surveillance studies, Patone et al. (2021) from the U.K. performed a self-control case series to examine the risk of cardiovascular adverse events from Covid-19 and Covid-19 vaccines.
They found that for young males, myocarditis risk is greatest from the second dose of Moderna’s mRNA vaccine, at 20.7-times in 16–39-year-olds (15 excess cases per 1 million people) and 12.3-times in males (excess cases n/a). Such myocarditis risks actually outweighed the same from Covid-19, standing at 5.1-times in 16–39-year-olds (10 excess cases per 1 million people) and 9.1-times in males (excess cases n/a).
It’s thus apparent that for younger males, the risk of myocarditis from the second dose of Moderna’s mRNA vaccine is greater than Covid-19.
Surveillance studies from Denmark, Finland, Norway, Sweden, and the U.S. have also reported that the risk of myocarditis is 2–4 fold greater after getting Pfizer-BioNTech’s than Moderna’s mRNA vaccine.
Notably, a newer surveillance study conducted by Patone et al. (2022) found that the risk of myocarditis from the third Moderna’s mRNA vaccine dose is lower than the second dose (2.6-fold vs. 11.2-fold increase). For Pfizer-BioNTech’s mRNA vaccine, myocarditis risk stood at 1.6-fold and 1.7-fold higher after the second and third doses, respectively.
But this newer analysis also found that myocarditis risk after the second dose of Moderna’s mRNA vaccine was higher than the risk after SARS-CoV-2 infection at 28-day follow-up (16.8-fold vs. 4.4-fold). And they also calculated 97 excess cases of myocarditis per 1 million young males (<40 years) who got the second dose of Moderna’s mRNA vaccine.
Patone et al. thus stated, “These findings may justify some reconsideration of the selection of vaccine type, the timing of vaccine doses, and the net benefit of booster doses in young people, particularly in young men.”
Risks are also cumulative. Taking three shots of Moderna’s mRNA vaccine means that the myocarditis risk is much higher than just taking two shots. So, young males may be better off not taking multiple shots of the mRNA vaccine and opting for another type of Covid-19 vaccine. And mRNA vaccines, Moderna’s in particular, may be best allocated to the older age groups who are not at risk of mRNA vaccine-related myocarditis.
Thankfully, myocarditis is rare. An increase of x (e.g., myocarditis) relative to a rare event will still be rare. This is reflected by the absolute increase of only 97 extra myocarditis cases per 1 million young males who got Moderna’s mRNA vaccine — despite a relative increase in risk by over 16-times — in the Patone et al. (2022) study. And 97 per million is just 0.01%.
Myocarditis from mRNA vaccines is also readily recoverable, typically within a week, and its fatality rate is close to 0%. Whereas myocarditis from virus infection is much more severe, where 50% of cases usually end up in intensive care, 25% don’t fully recover, and 10–20% die.
But any risk exposure — even though it’s by vaccination — is best avoided. To a young male, therefore, Moderna’s mRNA vaccine may not be the best one to take, especially at the second dose and perhaps at the third dose too.
Even if that’s not possible, Moderna’s mRNA vaccine is still likely to bring more benefits than harm, given that the risks of Covid-19 are manifold, not just myocarditis. Covid-19 is known to increase the risk of long-term issues, such as long-Covid (fatigue, brain fog, breathlessness, etc.) and other chronic diseases (e.g., heart attack, stroke, lung fibrosis, diabetes, etc.).