Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-alpha/gamma in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

Automated summary

After the outbreak of the SARS-CoV-2 pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although widespread immunity has been achieved through vaccination and infections, even individuals who have recovered from SARS-CoV-2 infection are recommended to receive BNT162b2 vaccination due to its effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. This study tracked changes in chromatin dynamics in peripheral blood mononuclear cells (PBMCs) of a patient who developed myocarditis after BNT162b2 vaccination, revealing alterations in interferon signaling and RUNX2/3 activity.