Probable Causes of mRNA Vaccine-Related Heart Inflammation

Shin

More questions on the risk-benefit analysis and proper injection technique of mRNA vaccines.

It’s rather uncomfortable to admit that vaccines have health risks, however safe they are in the vast majority.

In the context of influenza, febrile seizures (convulsions), Guillain–Barré syndrome (autoimmune nerve disorder), and anaphylaxis (severe allergic reaction) can happen from some of the seasonal flu shots. In the context of Covid-19, anaphylaxis can happen from many vaccines, severe blood clots plus low platelets from the DNA vaccines from AstraZeneca and J&J, and mild-to-severe heart inflammation from the mRNA vaccines from Pfizer and Moderna. Thankfully, these vaccine adverse events are scarce and unlikely to outweigh the risks of potential infections.

Still, it doesn’t hurt to study them further to see if there’s anything else we can do about it. As I’ve written about the 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 vaccines.

Common clinical signs of mRNA vaccine-related myocarditis and pericarditis are elevated troponin (a blood biomarker of heart muscle damage) levels, abnormal cardiac imaging scans, and chest pain. Other less common 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 the 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 were 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.

While there are many other studies on mRNA vaccine-induced heart inflammation with similar findings, the two discussed ones are of higher quality with larger sample sizes and proper control groups. From these two studies (and others), we know that mRNA vaccine-related myocarditis and pericarditis usually affect males under 40 years, regardless of any underlying medical conditions, within a week of getting the first or second dose (more commonly with the second dose).

Probable causes

First, it’s unlikely that infections caused myocarditis or pericarditis cases 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, an animal study published last month 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 apoptosis (programmed 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 biological 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 lead to 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.

So, the current C.D.C and W.H.O guidelines do not recommend aspiration before the 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 the best method of vaccine administration is.

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 authors of the animal study 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 blood clots plus low platelets) from the AstraZeneca and J&J DNA-based vaccines:

https://img.particlenews.com/image.php?url=1kC59Z_0c1sgbXQ00
Ledford (August 2021). Nature

Another hypothesis researchers have raised is molecular mimicry, where antibodies generated against the mRNA vaccine-encoded spike proteins also react against proteins of the heart, due to similarities in their protein structures. This might happen in individuals with a genetic or environmental predisposition to autoimmune disorders. 

One more probable/hypothetical cause of mRNA vaccine-related heart inflammation I learned from an email discussion is that the faster metabolism of younger males might overly metabolize the mRNA vaccine — creating more spike proteins that might generate more inflammation.

After all, in the context of Covid-19, 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 to train the immune system. 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 and non-DNA vaccines.

Risk-benefit analyses

Does this mean that younger males should get other types of Covid-19 vaccines? Honestly, it’s difficult to answer at this point.

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 possibly except for one news article and published 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 and 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 anti-inflammatory therapies. Long-term health consequences of mRNA vaccine-related heart inflammation are still open to debate, though.

Fourth, mRNA vaccines are one of the best vaccines we have against Covid-19, perhaps second to the Novavax subunit vaccine only. So, mRNA vaccines offer high protection against SARS-CoV-2, which can also cause heart inflammation that’s much more common and severe. In the Israel study mentioned above, for example, 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 Pfizer’s mRNA vaccine has already gained the first FDA approval given for a Covid-19 vaccine. The discovery of heart inflammation related to the mRNA vaccines 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 risk of potential SARS-CoV-2 infection. Otherwise, countries would have banned the use of mRNA vaccines in the younger age groups — like how the AstraZeneca DNA vaccine was banned for use in younger females due to risks of blood clots in many European countries.

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MSc Biology student | 5x first-author academic papers | 100+ articles on coronavirus | Freelance medical writer

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