Jack Zeitz

Introduction. After two years, COVD-19 still remains a public health threat as new strains continue to arise and spread throughout the world. The use of mRNA vaccines from Pfizer and Moderna have greatly reduced the burden of disease, and remains an effective way to avoid infection and stave off symptoms of COVID-19. However, the decision to receive one of the mRNA vaccines comes with a risk of developing myocarditis soon after the shot is received, which might deter some from becoming vaccinated. COVID vaccine-associated myocarditis (CVAM) occurs in approximately 1/83,000 people who receive any dose⁹, and causes symptoms such as severe chest pain, dyspnea, syncope, and palpitations. Subclinical symptoms include decreased systolic function and decreased left ventricular ejection fraction⁴. The exact molecular etiology of CVAM is what is investigated in this review, as it is not fully understood and could help identify a specific therapeutic target. Current CVAM therapy is purely aimed at symptom reduction, such as NSAIDs and Colchicine.^4,5 Methods. Because CVAM therapy is currently symptom-based, the discovery of the exact molecular mechanism of CVAM could allow for a more targeted therapy, and one that does not require hospitalization. Blood samples of patients with CVAM were taken during presentation to the ED in order to ascertain the mechanism of inflammation by which CVAM occurs. Results. Results of individual studies varied, but in general pointed to an increase in inflammatory cytokines in those with CVAM. In general, serum Troponin levels were elevated in most of the patients studied^1,2,3,4, as well as C-reactive protein levels in some patients.^2,3,4 One study noted that IL-5, IL-16, MIG, and IL-1ra were abnormally elevated in one patient with CVAM. IL-1ra is thought to be an anti-inflammatory biomarker, and is suspected in this case to act as a compensatory mechanism to reduce inflammation brought on by the inflammatory cytokines that are associated with it.² Conclusions. Because COVID-19 and CVAM are such novel phenomena, further research is needed in order to understand the exact molecular mechanism by which CVAM occurs. Possible therapeutics based on preliminary research include interleukin based therapeutics, such as exogenous IL-1ra that could be used to further downregulate inflammation in cardiac myocytes. NF-kB, a central inflammatory biomarker associated with CVAM, could also be manipulated in order to decrease CVAM symptoms. However, before any of these potential therapeutics can be tested, more research is needed in order to better understand the molecular mechanism of CVAM.

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2. Muthukumar A, Narasimhan M, Li Q-Z, et al. In-Depth Evaluation of a Case of Presumed Myocarditis After the Second Dose of COVID-19 mRNA Vaccine. Circulation. 2021;144(6):487-498. doi:10.1161/circulationaha.121.056038
3. Jain SS, Steele JM, Fonseca B, et al. COVID-19 Vaccination-Associated Myocarditis in Adolescents. Pediatrics. Published online August 13, 2021:e2021053427. doi:10.1542/peds.2021-053427
4. Truong DT, Dionne A, Muniz JC, et al. Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults. Circulation. Published online December 6, 2021. doi:10.1161/circulationaha.121.056583
5. Rosner CM, Genovese L, Tehrani BN, et al. Myocarditis Temporally Associated With COVID-19 Vaccination. Circulation. 2021;144(6):502-505. doi:10.1161/circulationaha.121.055891
6. Liu, T., Zhang, L., Joo, D. et al. NF-κB signaling in inflammation. Sig Transduct Target Ther 2, 17023 (2017). https://doi.org/10.1038/sigtrans.2017.23
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8. Bozkurt B, Kamat I, Hotez PJ. Myocarditis with covid-19 mrna vaccines. Circulation. 2021;144(6):471-484. doi:10.1161/circulationaha.121.056135