Scientists link specific gene variants to post-vaccination myocarditis and pericarditis

Scientists link specific gene variants to post-vaccination myocarditis and pericarditis

New genetic evidence shows why some people may be predisposed to myocarditis or pericarditis after COVID-19 vaccination, offering new insight into immune responses and vaccine safety.

Could your genes affect how your body responds to coronavirus disease 2019 (COVID-19)? Although heart inflammation following vaccination is rare, scientists have identified specific genetic variants that may increase the risk.

A recent study by a team of Swedish researchers published in the journalNPJ vaccinessheds light on why some people are developing messenger ribonucleic acid vaccines after receiving the Covid-19 messenger ribonucleic acid (mRNA).

Covid-19 vaccinations

Since the global rollout of Covid-19 vaccines, billions of doses have been administered to control the pandemic. While most side effects are mild, a small number of people, particularly young men, have heart inflammation, particularly myocarditis or pericarditis, heart inflammation, particularly myocarditis or pericarditis, shortly after receiving an mRNA vaccine. These conditions include inflammation of the heart muscle or surrounding sac, which typically occurs within a week of the second dose.

Current research suggests that these rare reactions may be linked to how the immune system responds to the vaccine, particularly the virus's spike protein. However, the exact biological mechanisms remain unclear. Factors such as age, sex hormones and pre-existing immune conditions have been suggested as contributors, but no clear genetic explanation has been confirmed.

About the study

This study was conducted using data from the Sweden Covid19 Myoperic Cohort, a group of 66 people in Sweden who developed myocarditis, pericarditis or perimyocarditis after receiving a COVID-19 vaccine. Participants were at least 18 years of age and had their diagnoses confirmed by healthcare professionals based on clinical records and cardiac imaging.

Only cases considered definitely or possibly related to vaccination were included. Each case was carefully evaluated using World Health Organization criteria, focusing on timing, symptoms and possible alternative explanations.

A control group of almost 5,000 people from the Swedish Twin Registry was also included. All participants provided blood or saliva samples and data on medical history, lifestyle, and medications. About 41% of patients made a full recovery within three months, while others experienced a prolonged or incomplete recovery. Both groups underwent genetic testing using high-throughput deoxyribonucleic acid (DNA) arrays with strict quality control steps to check missing information, rare variants and population differences.

The authors note that because these conditions are very rare, the sample size was small, which may limit the statistical certainty and generalizability of the results.

The researchers conducted a genome-wide association study using specialized software to find differences in DNA that might be linked to heart inflammation after vaccination. The analysis focused on identifying single nucleotide polymorphisms (SNPs), or subtle changes in DNA, that were more common in patients than controls.

Each case also underwent a comprehensive medical review. Patients received various standard cardiac tests such as electrocardiography, echocardiography and cardiac magnetic resonance imaging (MRI). Laboratory tests were performed to check for markers of inflammation and cardiac injury. Medical histories were also analyzed to understand other health conditions and medications that may have contributed to their reactions.

The aim of the study was to determine whether genetic variants could be linked to these rare but serious reactions. This could lead to personalized vaccine strategies and a better understanding of the immune response to mRNA vaccines.

Key insights

The study found that specific genetic variations may increase the risk of heart inflammation after receiving a CoVID-19 mRNA vaccine. In patients who developed pericarditis or perimyocarditis, three genetic variants near the Scaf11 gene were strongly associated with the disease. These variants, identified as RS536572545, RS146289966 and RS142297026, were much more common in affected individuals compared to the general population.

The SCAF11 gene is involved in pyroptosis, a form of cell death that causes intense inflammation. This connection suggested that people with certain versions of this gene may have an exaggerated inflammatory response to the vaccine. These findings were particularly strong in people who received the Comirnaty or Spikevax vaccines, both mRNA vaccines. No significant genetic associations were found when considering individual vaccines as Spikevax in myocarditis, and no significance was observed for the SCAF11 gene when stratified by the individual vaccine.

In myocarditis, another variant - RS570375365 in the LRRC4C gene - was significantly associated with cases occurring after Spikevax vaccination. This gene is known to play a role in immune signaling and has been linked to both heart and brain function. Variants in LRRC4C have also been associated with susceptibility to and severe outcomes of CoVID-19 in previous studies.

Despite their similar clinical features, these genetic findings suggest distinct biological pathways underlying myocarditis and pericarditis. The study authors caution that odds ratio (OR) estimates for these rare genetic variants should be interpreted carefully because statistical uncertainty is greater when little or no variation is seen among controls. The small sample size and the use of available clinical information and not globally used standardized diagnostic criteria demonstrated some limitations for drawing generalizable conclusions. Furthermore, diagnoses were made on the basis of clinical and imaging findings, rather than systematically applying international criteria such as those of the American College of Cardiology (ACC), the European Society of Cardiology (ESC), or the Brighton Collaboration, which could affect comparability with other studies. Proving a direct causal relationship between the vaccine and these conditions remains complex.

Conclusions

Overall, the results demonstrated a potential genetic association with rare occurrences of myocarditis and pericarditis following COVID-19 mRNA vaccination. By highlighting specific genes and inflammatory pathways, the study offered new leads to investigate why only certain people develop serious side effects after vaccination.

While further research is needed to confirm these results in larger groups, the study is an important step toward understanding individual responses to vaccination and improving public trust in immunization programs.

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