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. 2023 May 12;132(10):1302–1319. doi: 10.1161/CIRCRESAHA.123.321878

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© 2023 The Authors.

Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Figure 1. — Potential mechanisms leading to myocarditis/pericarditis following SARS-CoV-2 infection or vaccination. SARS-CoV-2 initially infects the lungs generating a cytokine storm including TNFα (tumor necrosis factor-alpha), IL (interleukin)-1β, and IL-6 and releasing extracellular vesicles (EVs) that contain virus or virus particles. 2. EVs may traffic through the blood or lymph to the heart where they infect cardiac cells that express the necessary receptors (ACE2 [angiotensin-converting enzyme 2], TMPRSS2 [transmembrane serine protease-2], and NRP1 [neuropilin-1 receptor]) such as cardiomyocytes, pericytes, mast cells, and macrophages. Additionally, resident antigen-presenting cells like mast cells, dendritic cells, and macrophages respond to virus and damaged cardiac tissue by activating an adaptive autoimmune response leading to myocarditis. 3. COVID-19 vaccines may activate resident mast cells or macrophages at the injection site that in susceptible individuals who have cardiac injury may promote an autoimmune response leading to myocarditis. Illustration credit: Sceyence Studios.