Unlocking Heart Inflammation Insights: A Deep Dive into the Differences Through Content Analysis

A group of Berlin researchers, working alongside international colleagues, have discovered variations in heart inflammation caused by COVID-19, anti-COVID vaccines, and non-COVID-related myocarditis. This finding opens up possibilities for more personalized therapies, as reported in “Nature Cardiovascular Research.”

Heart inflammation—or myocarditis—varies depending on its cause. A collaborative study led by Dr. Henrike Maatz from the Genetics and Genomics of Cardiovascular Diseases lab at Professor Norbert Hübner’s Max Delbrück Center in Berlin identified distinct immune signatures in myocarditis caused by SARS-CoV-2 infection and mRNA vaccines compared to non-COVID-19 myocarditis. The study was published in “Nature Cardiovascular Research.” Dr. Maatz, a co-lead author, stated, “We found clear differences in immune activation. This knowledge might help develop new and more personalized therapies tailored to specific types of inflammation.”

A Unique Opportunity During the Pandemic Myocarditis can be triggered by various factors including infections, autoimmune disorders, genetic and environmental elements, as well as rarely by vaccination. While COVID-19 primarily affects respiratory systems, it is known that SARS-CoV-2 infection can harm the heart too. In children and young adults, this virus often leads to multisystem inflammatory syndrome with myocarditis being a prominent feature—though this occurrence remains relatively rare.

When the coronavirus pandemic struck, researchers at Max Delbrück Center, Berlin Institute of Health (BIH) Charité, and Charité – Universitätsmedizin Berlin recognized an exceptional opportunity to examine if myocarditis varies on cellular and molecular levels based on its cause. Professor Norbert Hübner’s lab has a longstanding interest in studying cardiovascular diseases at the single-cell level. They partnered with Professor Carsten Tschöpe from Deutsches Herzzentrum der Charité (DHZC), head of BIH’s Immunocardiology research group, and principal investigator at Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK). The latter had been collecting biopsy samples from patients suspected to have myocarditis.

“At the DHZC, we have a widely recognized Myocarditis Unit specialized in performing endomyocardial biopsies in selected cases,” said Tschöpe. “The study program initiated by Charité during the COVID-19 crisis was integrated into their curriculum and forms part of the PERSONIFY Program supported by DZHK. Within this framework, patients with myocarditis undergo highly specific and targeted investigations, ensuring comprehensive and advanced evaluation both clinically and scientifically.”

“We are deeply grateful to our patients for their trust and invaluable contributions,” added Tschöpe. “Our specialist heart failure nurses have also played an essential role in identifying these patients, meticulously managing data, carefully handling tissue and blood samples, and providing overall patient care.”

Distinct Immune Activation Researchers at Max Delbrück Center performed single-nucleus RNA sequencing (snRNA-seq) on biopsied heart tissues to study gene expression patterns and create transcriptional profiles for each cell. These profiles helped identify the various types of cells within the heart. They then examined molecular changes in these cells as well as the abundance of different cell types across three groups: COVID-19 positive samples, cases caused by mRNA vaccines, and non-COVID myocarditis caused by viral infections prior to the pandemic.

Although there were similarities between inflammation triggered by various causes, researchers observed distinct immune signatures. For instance, post-COVID-19 myocarditis showed a stronger immune response compared with pre-pandemic forms of the condition. Additionally, they discovered a small population of T cells present in COVID-related myocarditis that was previously only found in the blood of severely ill COVID patients.

Implications for Treatment The ability to differentiate inflammation caused by different kinds of infections and vaccination could lead to better-targeted treatments. Dr. Maatz explains, “Based on this research, we might develop new therapies to control vaccine-related side effects.” Furthermore, given that biopsy samples from the heart are usually very small (about as large as a pinhead), obtaining useful data through snRNA-seq techniques was challenging.

However, according to Dr. Maatz, “the resolution and depth of insight we achieved really highlights the power of this method — perhaps it could be used in diagnostic settings in the future too.”