Mechanism clarified: Doctors have identified one of the causes of the very rare inflammation of the heart muscle after mRNA vaccinations against SARS-CoV-2. According to this, behind this myocarditis, which occurs primarily in young men, are special auto-antibodies that are formed against a central, anti-inflammatory molecule. In those affected, this receptor antagonist is slightly altered by attachment and therefore triggers the autoimmune reaction.

The mRNA vaccines against SARS-CoV-2 have proven to be an effective remedy against severe courses of Covid-19 – and thus an important weapon against the corona pandemic. However, the vaccination can lead to heart muscle inflammation in about one to ten cases in 100,000, especially in young men.

Unlike the much more common myocarditis after Covid-19 or other viral infections, this “vaccination myocarditis” is usually mild.

But what is behind it? A team led by Lorenz Thurner from the Saarland University Hospital in Homburg has now uncovered a mechanism for the development of this rare side effect of vaccination.

For their study, they immunologically examined 40 patients with biopsy-confirmed myocarditis after a SARS-CoV-2 vaccination and compared the data with that of 214 vaccinated healthy controls and 125 patients with myocarditis of other causes.

Specifically, the researchers were looking for a special autoantibody that had previously been increasingly found in patients with a severe course of Covid-19 and in children with multisystem inflammatory syndrome (MIS-C).

MIS-C, also known as PIMS – Pediatric Inflammatory Multisystem Syndrome – is a severe, body-wide inflammation that can occur a few weeks after acute coronavirus infection.

In fact, the team also found what they were looking for in the vaccinees with myocarditis: the blood of 75 percent of the young patients contained autoantibodies against a central endogenous anti-inflammatory called interleukin-1 receptor antagonist (IL-Ra). IL-Ra is a molecule that blocks the docking sites of the inflammatory messenger interleukin-1 on the surface of the cells and can thus stop excessive inflammatory immune reactions.

“Especially with regard to inflammation of the pericardium, heart muscle and blood vessels, we already know how important interleukin-1 is. However, our immune system normally regulates itself and highly potent interleukins in particular have natural opponents,” explains co-author Christoph Kessel from the University Hospital in Münster. However, even with severe courses of Covid-19 it was noticed that there are patients in whom one of these opponents, the interleukin-1 receptor antagonist, is switched off by mistakenly formed antibodies.

These antibodies have now also been detected in young men with vaccine-related myocarditis. But why do they appear with them? The team was also able to clarify this in their analyses: “Patients with myocarditis usually have an atypical form of IL-Ra with additional phosphorylation,” reports Thurner. In them, the molecule carries an additional phosphorus group at one point in its protein chain – something similar has already been demonstrated in children with MIS-C and adults with a severe course of Covid-19.

The problem with this is that this attachment to the IL-Ra molecule disrupts the recognition systems of the immune system: “The immune system then evaluates this as a foreign structure and mistakenly forms antibodies against it,” explains Thurner. “These then neutralize the important anti-inflammatory agent and thus promote the effect of pro-inflammatory messenger substances.”

However, it is still unclear why only some people temporarily develop attachments to their interleukin-1 receptor antagonists and thus irritate the immune system. This question still needs to be explored. Nevertheless, the detection of autoantibodies and atypical IL-Ra molecules sheds some light on the mechanisms by which vaccination can induce myocarditis in some people.

“In this context, however, it must be made clear that vaccinations against SARS-CoV-2 have prevented countless serious illnesses and saved many lives,” emphasizes co-author Karin Klingel from the University Hospital in Tübingen. “We strongly believe that the benefits of mRNA vaccination, with consequent protection against severe SARS-CoV-2 infection and serious complications, far outweigh the risk of mild myocarditis.” (New England Journal of Medicine, 2022; doi: 10.1056/NEJMc2205667)

Source: Saarland University

This article was written by Nadja Podbregar

The original of this post “Corona vaccination: The cause of heart muscle inflammation has been found” comes from scinexx.