It’s rather uncomfortable to admit that vaccines have health risks, however safe they are in the vast majority. For influenza vaccines, febrile seizures (convulsions), Guillain–Barré syndrome (autoimmune nerve disorder), and anaphylaxis (severe allergic reaction) can happen. For Covid-19, anaphylaxis can occur from many vaccines, severe and fatal blood clots from AstraZeneca and J&J DNA vaccines, and mild-to-severe heart inflammation from Pfizer and Moderna mRNA vaccines.
Thankfully, the risks of these vaccine adverse events are very low and don't outweigh the benefits that vaccines provide in most situations. Still, we should understand them further to see what we can do about it. As I’ve written about vaccine-related blood clots elsewhere, this article will focus on mRNA vaccine-related heart inflammation.
Risk of heart inflammation from mRNA vaccines
First, heart inflammation has three main types: myocarditis (inflamed heart muscles), pericarditis (inflamed outer linings of the heart), and endocarditis (inflamed inner linings of the heart). But only myocarditis and pericarditis have been associated with mRNA vaccine.
Common clinical signs of mRNA vaccine-related myocarditis and pericarditis are elevated troponin (a blood biomarker of heart muscle damage) levels, abnormal cardiac imaging, and chest pain. Other rarer symptoms include headache, breathlessness, fatigue, and body ache.
Previously in “mRNA Vaccine Safety and Risks: A One-Year Update From the U.S., U.K., and Israel,” I covered two new high-quality population-based studies that shed light on the risks of heart inflammation from mRNA vaccines. I’ll just describe their findings in brief here.
In one of them, researchers from Israel found that individuals vaccinated with Pfizer’s mRNA vaccine had a 3.24-times increased risk of myocarditis within 21 days of either the first or second dose compared to unvaccinated individuals. This equated to an excess of 2.7 events per 100,000 persons. About 90% of those myocarditis cases happened to males aged 20–34 years.
For the second study, researchers from the U.S. calculated that 12–39-year-olds had a 9.8-times increased risk of myocarditis/pericarditis at days 1–21 of vaccination compared to those at days 22–42 of vaccination. This gives an excess of 6.3 cases per million doses. More specifically, 85% of cases affected males, 85% occurred within seven days of vaccination (more commonly after the second dose), 82% led to hospitalization, and 6% led to the intensive care unit (ICU). But 0% of cases led to death.
There are many other studies on mRNA vaccine-related heart inflammation with similar findings too, but the two discussed ones are of higher quality with larger sample sizes and proper control groups. From those two studies, we know that mRNA vaccine-related heart inflammation usually affects males under 40 years, regardless of any underlying medical conditions, within a week of getting the first or, more commonly, the second dose.
First, it’s unlikely that infections had caused the myocarditis or pericarditis in recently vaccinated individuals. Several case series on this matter did not detect the presence of infections that can cause heart inflammation in recently vaccinated individuals. Yes, heart inflammation is usually caused by infections, including viruses (e.g., SARS-CoV-2, influenza virus, adenovirus, and coxsackievirus) and bacteria (e.g., S. aureus and M. tuberculosis).
Moving on, a published animal study offers clues to the probable cause of mRNA vaccine-related heart inflammation. This study examined the blood, tissue, and organ profiles of mice injected with Pfizer’s mRNA vaccine via the intramuscular (muscle) vs. intravenous (vein) route. Surprisingly, the intravenous route induced apoptotic cell death — as well as minor spike protein expression — in heart muscle cells, inflaming the heart muscles; that is, myocarditis. But the mice exhibited no symptoms of illness, suggesting that these biomolecular heart problems were not of clinical severity.
Neither myocarditis nor spike protein expression was present in mice in the intramuscular injection group. The authors then speculate that traces of mRNA vaccine entering the veins by accident during intramuscular injection might induce myocarditis and pericarditis in humans.
“The rare injection of a vaccine into a vein during planned intramuscular injection could contribute to the onset of myopericarditis,” an editorial of the study stated. “This is a relevant question since it is generally not recommended that a person administering the COVID-19 mRNA vaccine aspirate before injecting it into the deltoid muscle.”
Aspiration is the act of pulling back the syringe plunger to try to draw some blood before injecting the substance into the muscles. If blood is drawn, it means that the needle has punctured a blood vessel, and the needle is to be re-inserted. Aspiration has attracted controversies because it is a painful procedure with no confirmed benefits based on decades of research. This is because there are hardly any large blood vessels in the deltoid muscles.
Thus, the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) current guidelines don’t recommend aspiration before intramuscular injection of vaccines to minimize pain.
But in the context of the Covid-19 pandemic, where billions of vaccine doses have been given worldwide, we might see subtle harms in not practicing aspiration before intramuscular injection. Yet, there’s also no guarantee that the mass practice of aspiration would not be harmful. So, more research is needed to really know what’s the best method to administer vaccines.
That said, if traces of mRNA vaccine really entered the bloodstream after intramuscular injection, they might be able to enter the T tubules of heart muscle cells (cardiomyocytes) that are large enough to, in theory, allow the mRNA vaccine to pass through.
As the study authors explained: “Smaller mRNA-vaccine lipid-nanoparticles (100nm diameter) can be sucked into larger T tubules (diameter >200 nm) of cardiomyocytes during diastole, but not into T tubules of skeletal myocyte (diameter 20–40 nm). Thus, the T tubule system of cardiomyocytes may concentrate mRNA vaccine lipid-nanoparticles like a sponge.”
The same concern is also suspected for the probable cause of vaccine-induced thrombotic thrombocytopenia (severe and potentially fatal blood clots plus low platelets) from the AstraZeneca and J&J DNA-based vaccines:
Another hypothesis researchers have raised is molecular mimicry, where antibodies generated against the mRNA vaccine-encoded spike proteins also reacted against heart-related proteins due to similarities in their protein structures. This problem might happen in individuals with a genetic or environmental predisposition to autoimmune disorders.
One more hypothetical cause I learned from an email discussion is that the faster metabolism of younger males might overly metabolize the mRNA vaccine, possibly creating more spike proteins that might generate more inflammation.
After all, in the context of Covid-19 vaccines, the mRNA (and DNA) vaccine relies on the body to produce spike proteins to train the immune system. Older vaccine technology, in contrast, injects a set amount of spike proteins or inactivated virions. So, this hypothesis explains why mRNA vaccine-related heart inflammation affects younger adult males nearly all the time. And why such heart inflammation concerns have not been observed in young people receiving non-mRNA vaccines.
Notably, Moderna’s mRNA vaccine is associated with a 2.5-times increased risk of myocarditis than Pfizer’s. This finding makes sense given that Moderna’s mRNA vaccine dose (100 micrograms) is higher than Pfizer’s (30 micrograms), which could yield more spike protein production.
Does this mean that younger males should get other types of Covid-19 vaccines? Not really. At least for now, the benefits of mRNA vaccine still outweigh its potential risk of heart inflammation. But it might be a different story for vaccine boosters, as discussed below.
For one, mRNA vaccine-related heart inflammation is still very rare — at an excess of 2.7 cases per 100,000 persons or 6.3 cases per million doses, based on the abovementioned Israel and U.S. studies, respectively.
Second, no deaths have occurred from the hundreds of cases of mRNA vaccine-related heart inflammation in young adults in the U.S. so far. This is maybe except for one news article and case study. News from New Zealand reported that a woman (age undisclosed) died from myocarditis after a few days of getting the mRNA vaccine. In the case study, a 42-year-old male in the U.S. died of myocarditis and cardiogenic shock two weeks after getting the second dose of Moderna’s mRNA vaccine. But mRNA vaccine-related heart inflammation usually occurs in younger males within a week of vaccination, so the cause of death in those cases is still questionable.
Third, even though mRNA vaccine-related heart inflammation is not fatal, it can be severe enough to warrant hospitalization. But it usually resolves within days with standard anti-inflammatory treatment. Long-term health consequences of mRNA vaccine-related heart inflammation are still unclear, although the same applies to Covid-19 or long-Covid syndrome.
Fourth, mRNA vaccines are one of the best Covid-19 vaccines, only second to the Novavax subunit vaccine. So, mRNA vaccines offer high protection against SARS-CoV-2 that can also cause heart inflammation and injury that’s much more common and severe. For example, in the Israel study mentioned above, the risk of myocarditis in SARS-CoV-2-infected individuals is 18-times higher than uninfected individuals, giving an excess of 11 excess events per 100,000 persons. This number is only 2.7 excess when comparing vaccinated (with Pfizer’s mRNA) vs. unvaccinated individuals.
Fifth, mRNA vaccines are arguably the most studied Covid-19 vaccine thus far. The first FDA approval of a Covid-19 vaccine is Pfizer’s mRNA vaccine. The discovery of mRNA vaccine-related heart inflammation is also a testament to their extensively studied safety profile. Who knows, maybe other adverse events related to other Covid-19 vaccines won’t get known until later.
So, it seems that the risk of mRNA vaccine-related heart inflammation is unlikely to outweigh the benefits of mRNA vaccine. Otherwise, countries would have banned the use of mRNA vaccines in the younger age groups — like how the AstraZeneca DNA vaccine was prohibited for use in younger females due to risks of blood clots in many European countries.
The CDC’s Advisory Committee on Immunization Practices (ACIP) did a brilliant analysis of the risk (myocarditis) and benefits (prevented harms of Covid-19 based on infection rates as of May 2021 in the U.S.) of mRNA vaccine. While the study authors admit that long-Covid syndrome was not considered in the analysis, they concluded that the benefits of mRNA vaccine still outweigh its risk of myocarditis for all age and sex groups examined:
In the context of boosters, however, the risk-benefit analysis of mRNA vaccine in younger males is trickier. We know that immune responses are stronger from the second than the first vaccine dose, which also explains why heart inflammation occurs more often from the second mRNA vaccine dose. So, the third mRNA vaccine dose might generate greater immune responses than the second dose, possibly increasing the risk of heart inflammation.
Maybe using another type of Covid-19 vaccine as the third shot for young males vaccinated with mRNA vaccines might be the better booster. Such mixed vaccine regimens could also generate hybrid immunity that’s much more protective against SARS-CoV-2 variants than single-vaccine regimens. But hybrid immunity is still a rather new topic, so it’s also tough to answer what’s the best booster with certainty. The FDA, however, voted against the use of boosters for those <65 years last week. So, even the requirement for booster still needs more research, let alone which booster is best.
The CDC has advised that people who developed myocarditis or pericarditis after getting a dose of mRNA vaccine should avoid the next dose. But depending on the situation— such as the person’s risk of severe Covid-19 — the subsequent mRNA vaccine dose may still be recommended if the prior mRNA vaccine-related heart inflammation has completely healed.
The CDC admits that data is limited on whether people with a history of heart inflammation should get the mRNA vaccine, but continues to advise that as long as such history has fully resolved, the person should still get vaccinated. Both the CDC and Australian Government, however, don’t recommend that people with ongoing heart inflammation get the mRNA vaccine.
The Australian Government also states that “most pre-existing cardiac conditions are not regarded as contraindications to vaccination,” but further consultation with a healthcare professional is also advised (see the image below). Indeed, the evidence thus far, albeit limited, doesn't find pre-existing heart-related medical conditions as a risk factor for mRNA vaccine-related inflammation. But this might change as more research gets done.
In Hong Kong, only one dose of Pfizer’s mRNA vaccine is recommended for children aged 12–17 to reduce the risk of heart inflammation. Similarly, the U.K. and Norway have also decided to administer one mRNA vaccine dose to children aged 12–15 first, with the second dose’s requirement to be decided later, giving time for more research. This one-dose plan is sensible, given that the risk of mRNA vaccine-related heart inflammation is higher from the second than the first dose.
The Minister of Health of Singapore advises that people avoid strenuous exercise for two weeks after getting the mRNA vaccine, especially for males under 30 years. This advice is made based on the observation that mRNA vaccine-related heart complications can happen during strenuous exercise. The Central Epidemic Command Center of Taiwan has also made the same recommendation. While the precise reason behind such advice is unclear, strenuous exercise may put the heart under short-term stress that might trigger heart inflammation in mRNA vaccine recipients.
Lastly, one more probable precaution against mRNA vaccine-related heart inflammation may simply be to rest well after vaccination — to let the immune system work itself without additional unwanted inflammation. And many of our lifestyle choices are inflammatory to the body, such as over caloric overload (overeating), sleep deprivation, and psychological stress.