Document Type : Review articles


1 Faculty of Medicine, Trisakti University, Jakarta, Indonesia

2 Department of Occupational Medicine, Faculty of Medicine, Trisakti University, Jakarta, Indonesia

3 Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq

4 Department of Ophthalmology, Faculty of Medicine, Trisakti University, Jakarta, Indonesia


The unprecedented impact of the coronavirus disease-19 (COVID-19) pandemic on society and the global economy has highlighted the urgent need for an effective and safe vaccine. One of the very rare side effects of this vaccine is myocarditis, which was realized to be a terrible complication of the COVID-19 mRNA vaccine. A recent study showed an increase in 1824 events of myocarditis reported to VAERS, 383 (21.00%) reported after receiving a single dose of vaccine, then 956 (52.41%) after injection of the second dose. The most common complaint is chest pain that appears within 1 week after the injection. Young and male patients have a high incidence. The pathophysiology of post-mRNA vaccination myocarditis remains unclear, with one study hypothesizing it to be due to hypersensitivity myocarditis and another study suggesting another possible mechanism is molecular mimicry. The main aim of this literature review is to improve knowledge, prevention, and management, as well as determine the incidence between the COVID-19 mRNA vaccine and myocarditis.


Main Subjects

[1]      H. Q. J. Al-Ani, N. N. Al-Hayani, and R. M. Al-Ani, “Efficacy of the Examination of Saliva Sample by Reverse Transcriptase-Polymerase Chain Reaction in Detection of SARS-CoV-2 in Al-Fallujah City, Iraq,” J. Pure Appl. Microbiol. 16(4):2416-2424, 2022.
[2]      J. S. Tregoning, K. E. Flight, S. L. Higham, Z. Wang, and B. F. Pierce, “Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape,” Nat. Rev. Immunol., vol. 21, no. 10, pp. 626–636, 2021.
[3]      A. G. Hadi, M. Kadhom, E. Yousif, and N. Hairunisa, “In COVID-19 time, how to protect myself and others? a review,” J. biomedika dan Kesehat., vol. 3, no. 3, pp. 153–158, 2020.
[4]      M. M. Higdon et al., “A systematic review of coronavirus disease 2019 vaccine efficacy and effectiveness against severe acute respiratory syndrome coronavirus 2 infection and disease,” in Open Forum Infectious Diseases. vol. 9, no. 6, p. ofac138, 2022.
[5]      L. R. Baden et al., “Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine,” N. Engl. J. Med., vol. 384, no. 5, pp. 403–416, 2021.
[6]      A. Fazlollahi et al., “Cardiac complications following mRNA COVID‐19 vaccines: A systematic review of case reports and case series,” Rev. Med. Virol., vol. 32, no. 4, p. e2318, 2022.
[7]      Y. Perez et al., “Myocarditis following coronavirus disease 2019 mRNA vaccine: a case series and incidence rate determination,” Clin. Infect. Dis., vol. 75, no. 1, pp. e749–e754, 2022.
[8]      N. S. Hendren, M. H. Drazner, B. Bozkurt, and L. T. Cooper Jr, “Description and proposed management of the acute COVID-19 cardiovascular syndrome,” Circulation, vol. 141, no. 23, pp. 1903–1914, 2020.
[9]      B. Bozkurt, I. Kamat, and P. J. Hotez, “Myocarditis with COVID-19 mRNA vaccines,” Circulation, vol. 144, no. 6, pp. 471–484, 2021.
[10]    A. Luk et al., “Myocarditis and pericarditis after COVID-19 mRNA vaccination: practical considerations for care providers,” Can. J. Cardiol., vol. 37, no. 10, pp. 1629–1634, 2021.
[11]    C. Tschöpe et al., “Myocarditis and inflammatory cardiomyopathy: current evidence and future directions,” Nat. Rev. Cardiol., vol. 18, no. 3, pp. 169–193, 2021.
[12]    A. L. P. Caforio et al., “Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases,” Eur. Heart J., vol. 34, no. 33, pp. 2636–2648, 2013.
[13]    A. Pollack, A. R. Kontorovich, V. Fuster, and G. W. Dec, “Viral myocarditis—diagnosis, treatment options, and current controversies,” Nat. Rev. Cardiol., vol. 12, no. 11, pp. 670–680, 2015.
[14]    M. Olejniczak, M. Schwartz, E. Webber, A. Shaffer, and T. E. Perry, “Viral myocarditis—Incidence, diagnosis and management,” J. Cardiothorac. Vasc. Anesth., vol. 34, no. 6, pp. 1591–1601, 2020.
[15]    O. Narovlyanskaya and E. J. Winokur, “Viral myocarditis,” Dimens. Crit. Care Nurs., vol. 39, no. 2, pp. 75–80, 2020.
[16]    C. Buttà, L. Zappia, G. Laterra, and M. Roberto, “Diagnostic and prognostic role of electrocardiogram in acute myocarditis: A comprehensive review,” Ann. Noninvasive Electrocardiol., vol. 25, no. 3, p. e12726, 2020.
[17]    M. Nassar et al., “Corrigendum to ‘COVID-19 vaccine-induced myocarditis case report with literature review’[Diabetes & Metabolic Syndrome: Clinical Research & Reviews Volume 15, Issue 5, September–October 2021, 102205],” Diabetes Metab. Syndr., vol. 15, no. 5, p. 102277, 2021.
[18]    K. B. Lewandrowski, “Special Topics: Cardiac Markers in Myocarditis: Cardiac Transplant Rejection and Conditions Other than Acute Coronary Syndrome,” Clin. Lab. Med., vol. 34, no. 1, pp. 129–135, 2014.
[19]    S. C. Smith, J. H. Ladenson, J. W. Mason, and A. S. Jaffe, “Elevations of cardiac troponin I associated with myocarditis: experimental and clinical correlates,” Circulation, vol. 95, no. 1, pp. 163–168, 1997.
[20]    W. Dwijanarko, H. Mumpuni, and B. Irawan, “Current diagnosis and management of myocarditis,” ACI (Acta Cardiol. Indones., vol. 2, no. 2, 2016.
[21]    T. Lampejo, S. M. Durkin, N. Bhatt, and O. Guttmann, “Acute myocarditis: aetiology, diagnosis and management,” Clin. Med. (Northfield. Il)., vol. 21, no. 5, p. e505, 2021.
[22]    J. A. Luetkens et al., “Comparison of original and 2018 Lake Louise criteria for diagnosis of acute myocarditis: results of a validation cohort,” Radiol. Cardiothorac. Imaging, vol. 1, no. 3, p. e190010, 2019.
[23]    P. Anand and V. P. Stahel, “The safety of Covid-19 mRNA vaccines: A review,” Patient Saf. Surg., vol. 15, no. 1, pp. 1–9, 2021.
[24]    S. Pascolo, “Synthetic messenger RNA-based vaccines: from scorn to hype,” Viruses, vol. 13, no. 2, p. 270, 2021.
[25]    J. W. Park, P. N. P. Lagniton, Y. Liu, and R.-H. Xu, “mRNA vaccines for COVID-19: what, why and how,” Int. J. Biol. Sci., vol. 17, no. 6, p. 1446, 2021.
[26]    Q. Huang, J. Zeng, and J. Yan, “COVID-19 mRNA vaccines,” J. Genet. Genomics, vol. 48, no. 2, pp. 107–114, 2021.
[27]    O. Parés-Badell et al., “Local and systemic adverse reactions to mRNA COVID-19 vaccines comparing two vaccine types and occurrence of previous COVID-19 infection,” Vaccines, vol. 9, no. 12, p. 1463, 2021.
[28]    W. Woo et al., “Clinical characteristics and prognostic factors of myocarditis associated with the mRNA COVID‐19 vaccine,” J. Med. Virol., vol. 94, no. 4, pp. 1566–1580, 2022.
[29]    S. A. Mouch et al., “Myocarditis following COVID-19 mRNA vaccination,” Vaccine, vol. 39, no. 29, pp. 3790–3793, 2021.
[30]    R. Kornowski and G. Witberg, “Acute myocarditis caused by COVID-19 disease and following COVID-19 vaccination,” Open Hear., vol. 9, no. 1, p. e001957, 2022.
[31]    M. E. Oster et al., “Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021,” Jama, vol. 327, no. 4, pp. 331–340, 2022.
[32]    S. Hassanzadeh, S. Sadeghi, A. Mirdamadi, and A. Nematollahi, “Myocarditis following AstraZeneca (an adenovirus vector vaccine) COVID‐19 vaccination: A case report,” Clin. Case Reports, vol. 10, no. 4, p. e05744, 2022.
[33]    R. R. Ling et al., “Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis,” Lancet Respir. Med. 10(7): 679–688, 2022.
[34]    M. Ali et al., “COVID-19 and myocarditis: a review of literature,” Egypt. Hear. J., vol. 74, no. 1, pp. 1–9, 2022.
[35]    S. Cushion, V. Arboleda, Y. Hasanain, M. D. Beckler, P. Hardigan, and M. M. Kesselman, “Comorbidities and symptomatology of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related myocarditis and SARS-CoV-2 vaccine-related myocarditis: a review,” Cureus, vol. 14, no. 4, 2022.
[36]    A. Simone et al., “Acute myocarditis following COVID-19 mRNA vaccination in adults aged 18 years or older,” JAMA Intern. Med., vol. 181, no. 12, pp. 1668–1670, 2021.
[37]    D. Gubernot et al., “US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines,” Vaccine, vol. 39, no. 28, pp. 3666–3677, 2021.
[38]    S. Lane, A. Yeomans, and S. Shakir, “Reports of myocarditis and pericarditis following mRNA COVID-19 vaccination: a systematic review of spontaneously reported data from the UK, Europe and the USA and of the scientific literature,” BMJ Open, vol. 12, no. 5, p. e059223, 2022.
[39]    A. A. Shiravi, A. Ardekani, E. Sheikhbahaei, and K. Heshmat-Ghahdarijani, “Cardiovascular complications of SARS-CoV-2 vaccines: an overview,” Cardiol. Ther. 11(1): 13–21, 2022.
[40]    A. Matta et al., “Clinical presentation and outcomes of myocarditis post mRNA vaccination: a meta-analysis and systematic review,” Cureus, vol. 13, no. 11, 2021.
[41]    J. Montgomery et al., “Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military,” JAMA Cardiol., vol. 6, no. 10, pp. 1202–1206, 2021.
[42]    M. Fraser et al., “COVID-19-associated myocarditis: an evolving concern in cardiology and beyond,” Biology (Basel)., vol. 11, no. 4, p. 520, 2022.
[43]    S. Heymans and L. T. Cooper, “Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms,” Nat. Rev. Cardiol., vol. 19, no. 2, pp. 75–77, 2022.
[44]    J. W. Gargano et al., “Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021,” Morb. Mortal. Wkly. Rep., vol. 70, no. 27, p. 977, 2021.
[45]    J. H. Chen et al., “COVID-19 vaccine-related myocarditis: a descriptive study of 40 case reports,” Cureus, vol. 14, no. 1, 2022.
[46]    S. Le Vu et al., “Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines,” Nat. Commun., vol. 13, no. 1, p. 3633, 2022.
[47]    T. Licata and A. Clements, “Case Report of COVID-19 mRNA Vaccine-Associated Myocarditis,” WMJ Off. Publ. State Med. Soc. Wisconsin, vol. 121, no. 3, pp. E50–E52, 2022.
[48]    S. Choi et al., “Myocarditis-induced sudden death after BNT162b2 mRNA COVID-19 vaccination in Korea: case report focusing on histopathological findings,” J. Korean Med. Sci., vol. 36, no. 40, 2021.
[49]    A. K. Verma, K. J. Lavine, and C.-Y. Lin, “Myocarditis after Covid-19 mRNA vaccination,” N. Engl. J. Med., vol. 385, no. 14, pp. 1332–1334, 2021.
[50]    V. Kytö, J. Sipilä, and P. Rautava, “The effects of gender and age on occurrence of clinically suspected myocarditis in adulthood,” Heart, vol. 99, no. 22, pp. 1681–1684, 2013.
[51]    A. Arola, E. Pikkarainen, J. O. T. Sipilä, J. Pykäri, P. Rautava, and V. Kytö, “Occurrence and features of childhood myocarditis: a nationwide study in Finland,” J. Am. Heart Assoc., vol. 6, no. 11, p. e005306, 2017.
[52]    X. Huang, Y. Sun, G. Su, Y. Li, and X. Shuai, “Intravenous immunoglobulin therapy for acute myocarditis in children and adults a meta-analysis,” Int. Heart J., vol. 60, no. 2, pp. 359–365, 2019.
[53]    M. Kang, F. Mo, M. Witmans, V. Santiago, and M. A. Tablizo, “Trends in Diagnosing Obstructive Sleep Apnea in Pediatrics,” Children, vol. 9, no. 3, p. 306, 2022.
[54]    H. Zhao et al., “Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size,” Biomed. Pharmacother., vol. 133, p. 110825, 2021.