Covid-19 Vaccine-Associated Myocarditis, Autopsied: A Brief Tabulated Review of the Autopsy Literature

The direct relationship between SARS-CoV-2 infection and myocarditis remains tenuous at best.  Recent ecological (1), controlled retrospective cohort (2), and autopsy (3) data do not support an association. This overall absence of support for a specific “SARS-CoV-2 myocarditis syndrome” from focused autopsy studies of presumed myocarditis deaths (3) is consistent with findings from general necropsy studies of covid-19 deaths (4,5,6). These investigations have established SARS-CoV-2 infection leading to fatal covid-19 is indeed, as the name implies, a respiratory illness. Wong et al (4), for example, described how, “No overt pathological findings attributable to SARS-CoV-2 infection could be recognized outside of the lung…[B]eyond the respiratory tract [SARS-CoV-2 infection] does not induce any major pathology…in fatal cases.”

A systematic review of [primarily] spontaneously reported data from the UK, USA and European Union/European Economic Area (EU/EEA) beginning with vaccine launch, through mid-March, 2022, found 0.22% (n=30) of 13, 571 covid vaccine-associated myocarditis or pericarditis events were fatal (7). These data are complemented by a much smaller, but growing autopsy literature (8,9,10,11,12).  The limited necropsy data characterizing covid-19 vaccine-associated decedents with myocarditis/myopericarditis repeatedly affirm cardiac pathologies directly attributable to very recent vaccination. Such findings contrast with the lack of definitive epidemiologic (1,2,3), or autopsy evidence (3) for a unique SARS-CoV-2 infection myocarditis, the latter as described by Caforio et al (3): Strong evidence for a SARS-CoV-2 role in direct infection of cardiac myocytes leading to virus induced myocarditis in patients is missing… [T]here is not yet definitive EMB [endomyocardial biopsy]/autopsy proof that SARS-CoV-2 causes direct cardiomyocyte damage in association with histological myocarditis.”

Tables 1-3 detail the published autopsy findings (8-12) from six fatal cases of post-covid mRNA vaccine-associated myocarditis. The etiologies for cases 1 and 2 were most consistent with an epinephrine-mediated “toxic myocarditis,” whereas cases 3-6 evidenced hyperinflammatory myocarditis. Ultimately, after extensive investigation, each case was deemed a covid vaccine caused fatal myocarditis.

References

1) Aquaro GD, Licordari R, Todiere G, Ianni U, Dellegrotaglie S, Restivo L, Grigoratos C, Patanè F, Barison A, Micari A, Di Bella G. Incidence of acute myocarditis and pericarditis during the coronavirus disease 2019 pandemic: comparison with the prepandemic period. J Cardiovasc Med (Hagerstown). 2022 Jul 1;23(7):447-453. doi: 10.2459/JCM.0000000000001330. Epub 2022 Jun 23. PMID: 35763765

2) Tuvali O, Tshori S, Derazne E, Hannuna RR, Afek A, Haberman D, Sella G, George J. The Incidence of Myocarditis and Pericarditis in Post COVID-19 Unvaccinated Patients-A Large Population-Based Study. J Clin Med. 2022 Apr 15;11(8):2219. doi: 10.3390/jcm11082219. PMID: 35456309; PMCID: PMC9025013.

3) Caforio ALP, Baritussio A, Basso C, Marcolongo R. Clinically Suspected and Biopsy-Proven Myocarditis Temporally Associated with SARS-CoV-2 Infection. Annu Rev Med. 2022 Jan 27;73:149-166. doi: 10.1146/annurev-med-042220-023859. Epub 2021 Sep 10. PMID: 34506211.

4) Wong DWL, Klinkhammer BM, Djudjaj S, Villwock S, Timm MC, Buhl EM, Wucherpfennig S, Cacchi C, Braunschweig T, Knüchel-Clarke R, Jonigk D, Werlein C, Bülow RD, Dahl E, von Stillfried S, Boor P. Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients. Cells. 2021 Jul 27;10(8):1900. doi: 10.3390/cells10081900. PMID: 34440669; PMCID: PMC8394956.

5) Edler C, Schröder AS, Aepfelbacher M, Fitzek A, Heinemann A, Heinrich F, Klein A, Langenwalder F, Lütgehetmann M, Meißner K, Püschel K, Schädler J, Steurer S, Mushumba H, Sperhake JP. Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany. Int J Legal Med. 2020 Jul;134(4):1275-1284. doi: 10.1007/s00414-020-02317-w. Epub 2020 Jun 4. Erratum in: Int J Legal Med. 2020 Sep;134(5):1977. PMID: 32500199; PMCID: PMC7271136.

6) Remmelink M, De Mendonça R, D’Haene N, De Clercq S, Verocq C, Lebrun L, Lavis P, Racu ML, Trépant AL, Maris C, Rorive S, Goffard JC, De Witte O, Peluso L, Vincent JL, Decaestecker C, Taccone FS, Salmon I. Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care. 2020 Aug 12;24(1):495. doi: 10.1186/s13054-020-03218-5. PMID: 32787909; PMCID: PMC7422463.

7) Lane S, Yeomans A, Shakir S. 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. 2022 May 25;12(5):e059223. doi: 10.1136/bmjopen-2021-059223. Erratum in: BMJ Open. 2022 Jul 5;12(7):e059223corr1. PMID: 35613761; PMCID: PMC9133727.

8) Gill JR, Tashjian R, Duncanson E. Autopsy Histopathologic Cardiac Findings in 2 Adolescents Following the Second COVID-19 Vaccine Dose. Arch Pathol Lab Med. 2022 Aug 1;146(8):925-929. doi: 10.5858/arpa.2021-0435-SA. PMID: 35157759. (cases a & b)

9) Verma AK, Lavine KJ, Lin CY. Myocarditis after Covid-19 mRNA Vaccination. N Engl J Med. 2021 Sep 30;385(14):1332-1334. doi: 10.1056/NEJMc2109975. Epub 2021 Aug 18. PMID: 34407340; PMCID: PMC8385564.

10) Choi S, Lee S, Seo JW, Kim MJ, Jeon YH, Park JH, Lee JK, Yeo NS. Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings. J Korean Med Sci. 2021 Oct 18;36(40):e286. doi: 10.3346/jkms.2021.36.e286. PMID: 34664804; PMCID: PMC8524235.

11) Ameratunga R, Woon ST, Sheppard MN, Garland J, Ondruschka B, Wong CX, Stewart RAH, Tatley M, Stables SR, Tse RD. First Identified Case of Fatal Fulminant Necrotizing Eosinophilic Myocarditis Following the Initial Dose of the Pfizer-BioNTech mRNA COVID-19 Vaccine (BNT162b2, Comirnaty): an Extremely Rare Idiosyncratic Hypersensitivity Reaction. J Clin Immunol. 2022 Apr;42(3):441-447. doi: 10.1007/s10875-021-01187-0. Epub 2022 Jan 3. PMID: 34978002; PMCID: PMC8720536.

12) Hoshino N, Yanase M, Ichiyasu T, Kuwahara K, Kawai H, Muramatsu T, Ishii H, Tsukamoto T, Morimoto SI, Izawa H. An autopsy case report of fulminant myocarditis: Following mRNA COVID-19 vaccination. J Cardiol Cases. 2022 Jul 4. doi: 10.1016/j.jccase.2022.06.006. Epub ahead of print. PMID: 35812802; PMCID: PMC9250935.

 

 

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