Medicine and Research
Covid-19 Vaccines: Cause of Heart Muscle Inflammation Detected
Auto-antibodies responsible for rare side effect
Myocarditis develops in up to ten out of every one hundred thousand patients after mRNA vaccination against Corona. In particular younger male patients are affected by this rare side effect. Unlike the much more common myocarditis following covid 19 infection, the disease after vaccination is usually very mild. But what exactly is the trigger? An international team of researchers led by hematologist and cancer specialist Lorenz Thurner from Saarland University Hospital has discovered a mechanism behind this in their research.
Various meta-studies had shown that mainly male patients between 14 and 30 years of age developed myocarditis after mRNA vaccination, typically after the second vaccine dose. Researchers also found an auto-antibody in the blood of children and adolescents who were severely ill with PIMS, also called multisystemic inflammatory syndrome (MIS-C), or had a severe course of Covid 19.
Eliminating a Key Antagonist
"We know that the messenger interleukin-1 (IL-1) can trigger inflammation of the pericardium, the heart muscle, but also inflammation throughout the body. Its endogenous counterpart is the so-called interleukin-1 receptor antagonist (IL-1Ra). This prevents interleukin-1 signaling and thereby inhibits inflammation. However, the auto-antibodies disable this antagonist," explains Lorenz Thurner. The research team wondered whether the same mechanism could also be responsible for the development of the rare vaccine side effect.
Confusion in the Cell Provides Free Play
The researchers examined blood and plasma from 40 patients with biopsy-determined myocarditis following SARS-CoV-2 vaccination. They compared the data with those of 214 vaccinated healthy comparison subjects and 125 patients with myocarditis who had contracted it before the pandemic. And indeed, the 40 patients had the same auto-antibody. "We found that the interleukin-1 receptor antagonist in these patients carries an additional phosphate residue at one point in its protein chain. This change is recognized by the specific immune system as foreign, so that the body's own defense player IL-1Ra is instead "read" as a potential external troublemaker and then neutralized by the antibodies. This gives the inflammatory messenger interleukin-1 free rein, resulting in a dangerous imbalance," says Lorenz Thurner.
Research Success Through Interdisciplinary Collaboration
Decisive for this proof was the cooperation in an interdisciplinary team. In addition to the hematologist Lorenz Thurner, the team included the pediatric cardiologist Jochen Pfeifer and the cardiologist Michael Böhm from Saarland University Hospital in Homburg, the pathologist Karin Klingel from Tübingen University Hospital, who specializes in myocarditis, the pediatric pneumologist Bernhard Thurner from the Allgäu Hospital Association, the immunologist Christoph Kessel from Münster University Hospital, who specializes in hyperinflammation, as well as researchers at the Competence Network for Congenital Heart Defects and cardiologists from Germany and Israel participated in the research.
Finally a Clearer Picture
Why this change in the interleukin-1 receptor antagonist is found primarily in male patients between the ages of 14 and 30, how exactly the hyperphosphorylation of IL-1Ra occurs, and whether it actually also triggers the autoimmune response can now be further explored. "Now we have a clearer picture of the mechanisms and know what to look for, for example, also in connection with the severe sequelae in Covid-19," says Jochen Pfeifer.
mRNA Vaccination Remains Urgent Recommendation
Nevertheless, Hashim Abdul-Khaliq and Michael Böhm, together with their colleagues, continue to explicitly recommend mRNA vaccination, especially for patients with congenital heart defects: "The rare side effect of mRNA vaccination is disproportionate to its great benefit. Vaccine-induced myocarditis is readily treatable. The same cannot be said of the much more common covid-19 myocarditis. It is far more threatening," says Hashim Abdul-Khaliq, Director of Pediatric Cardiology at Saarland University Hospital and Vice Chairman of the Board of the Competence Network for Congenital Heart Defects.
Scientific Details of the Study
Learn more about the study design, material and methods, as well as the background of the study:
IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination.
Thurner L, Kessel C, Fadle N, Regitz E, Seidel F, Kindermann I, Lohse S, Kos I, Tschöpe C, Kheiroddin P, Kiblboeck D, Hoffmann MC, Bette B, Carbon G, Cetin O, Preuss KD, Christofyllakis K, Bittenbring JT, Pickardt T, Fischer Y, Thiele H, Baldus S, Stangl K, Steiner S, Gietzen F, Kerber S, Deneke T, Jellinghaus S, Linke A, Ibrahim K, Grabmaier U, Massberg S, Thilo C, Greulich S, Gawaz M, Mayatepek E, Meyer-Dobkowitz L, Kindermann M, Birk E, Birk M, Lainscak M, Foell D, Lepper PM, Bals R, Krawczyk M, Mevorach D, Hasin T, Keren A, Kabesch M, Abdul-Khaliq H, Smola S, Bewarder M, Thurner B, Böhm M, Pfeifer J, Klingel K
The New England journal of medicine, (2022). Show this publication on PubMed.