Another Scientific Study finds myocarditis to be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination

Another Scientific Study finds myocarditis to be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination

The reason autopsies are not done in the case of vaccine-related deaths is to prevent the information from coming out that the Covid “vaccine” is deadly.

Several cases of myocarditis following anti-SARS-CoV-2 vaccination have been published [4,5,6, 9, 14]. Symptoms typically occur within the first three days following the second dose of mRNA COVID-19 vaccines (Comirnaty and Spikevax, respectively) and young male patients presenting with chest pain are predominantly affected. Clinical findings like elevated troponin serum levels, abnormal ST-elevations in ECG and altered ventricle movement in echocardiogram or late enhancement in cardiac MRI suggested the development of a myocarditis. Most of the reported cases showed clinically mild courses with resolution of symptoms without treatment. However, in rare instances individuals required intensive care support or even died from acute heart failure as described in an early report by Verma et al. [9]. These studies, with their different diagnostic modalities applied, already pointed to a link between vaccination and myocarditis, though many of these studies lack extensive testing for infectious agents. In particular studies of autopsy cohorts as well as information about potential long-term outcomes are not available yet [15,16,17].

Through our autopsy-based approach, we identified five cases of lymphocytic (epi-)myocarditis in persons, who were unexpectedly found dead at home within the first week following mRNA-mediated anti-SARS-CoV-2 immunization. According to the Dallas criteria four samples were classified as definitive myocarditis. In the remaining case, comparable inflammatory infiltration of the epicardium, subepicardial fat and myocardium was found, but myocardial infiltration did not exceed the threshold of the Dallas criteria. All cases showed a consistent phenotype: (A) focal interstitial lymphocytic myocardial infiltration, in three cases accompanied by demonstrable microfocal myocyte destruction. (B) T-cell dominant infiltrate with CD4 positive T-cells outnumbering CD8 positive T-cells by far; (C) frequently associated with T-cell infiltration of epicardium and subepicardial fat tissue revealing a similar immune phenotype (CD4 >  > CD8).

As well-known from myocardial infarction, it has to be considered that microscopically visible manifestation of myocardial damage under such acute conditions may lag behind function; this may relate to aspects of infiltrate composition, such as the relatively low macrophage content, or the histologically focal myocyte damage. Thus, functional effects may be much stronger than expected considering the histological picture. This is reflected by the fact that myocarditis is a major cause of sudden and unexpected death in infants, adolescents, and young adults with frequencies ranging from 1 to 14% among the young [18,19,20,21]. As outlined in the materials and methods section, evaluation of the likelihood of an AEFI reflects the temporal association and the autopsy findings (with exclusion of other reasons of sudden death), and negative molecular testing for potential infectious causes. Thus, case 5 with HHV6-DNA detected at low copy numbers was classified as possible. In general, a causal link between myocarditis and anti-SARS-CoV-2 vaccination is supported by several considerations: (A) a close temporal relation to vaccination; all cases were found dead within one week after vaccination, (B) absence of any other significant pre-existing heart disease, especially ischaemic heart disease or cardiomyopathy, (C) negative testing for potential myocarditis-causing infectious agents, (D) presence of a peculiar CD4 predominant T-cell infiltrate, suggesting an immune mediated mechanism. The latter criterion is supported by demonstration of a phenotypically identical T-cell infiltrate at the deltoidal injection site in one of the cases. It has to be emphasized, that a comparable (epi-)myocardial infiltration was neither found in any of the other 20 autopsies performed on bodies found dead within 20 days following an anti-SARS-CoV-2 vaccination nor in the age- and sex-matched cohorts from three independent periods from our autopsy-files.

Based on the autopsy findings and all available data, no other cause of death except (epi-)myocarditis was identified in any of the cases presented here. Hence, myocarditis has to be considered the likely cause of death. From a functional point of view, myocardial damage in our cases is not sufficient to postulate contractile failure as terminal cause of death; thus, arrhythmic failure, either by cardiac arrest or by ventricular fibrillation, has to be assumed as the mechanism leading to the patients’ death. Myocarditis-related acute cardiac arrest due to either asystoly or ventricular fibrillation is a well-established pathomechanism in other causes of acute myocarditis as well [22, 23].

Regarding the potential underlying pathogenesis of (epi-)myocarditis, our findings allow some considerations. Besides pneumonia, myocarditis is another manifestation reported during SARS-CoV-2-infection [24]. It is under debate whether myocarditis in COVID-19 is primarily caused by the viral infection or whether it occurs secondary as a consequence of the host´s immune response, in particular by T-lymphocyte-mediated cytotoxicity or as a consequence of the cytokine storm observed during COVID-19 [25]. Thus, it seems possible that a molecular mimicry between the spike protein of SARS-CoV-2 and self-antigens may trigger an anti-myocytic immune response in predisposed individuals. Multiple studies of mRNA-vaccines showed robust Receptor-Binding-Domain specific antibodies, T cell and cytokine responses [26]. T cells, especially CD4 + T cells, are the main drivers of heart-specific autoimmunity in myocarditis [27]. A vaccine-induced activation of the immune system in persons with otherwise peripheral tolerance due to regulatory T cells might promote CD4 + effector T cell expansion and myocarditis. Considering that (epi-)myocarditis has not been described following vector-based anti-SARS-CoV-2 immunization yet, it could also be possible that the immune response may be directed against the mRNA or other constituents of the vaccine formula. However, the vaccine against smallpox, based on a vaccinia virus, is reported to cause (epi-)myocarditis in rare cases [2, 3]. Of note, it has been recently reported that intravenous injection of COVID-19 mRNA vaccine is able to induce an acute (epi-) myocarditis in a preclinical model [28]. Interestingly, we recorded inflammatory foci predominantly in the right heart, which may suggest a gradual blood-stream derived dilution effect and based on this finding it is at least tempting to speculate that inadvertent intravascular vaccine injection may be contributive.

Our study is limited by the relatively small cohort size and inherits the bias of an endpoint analysis. The nature of our autopsy study necessitates that the data are descriptive in quality and does not allow any epidemiological conclusions in terms of incidence or risk estimation. The reported incidence of (epi-)myocarditis after vaccination is low and the risks of hospitalization and death associated with COVID-19 are stated to be greater than the recorded risk associated with COVID-19 vaccination [29]. Importantly, infectious agents may also cause lymphocytic myocarditis with a similar immunophenotype, thus meticulous molecular analyses is required in all cases of potentially vaccination-associated myocarditis.

Regarding a potential auto-immunological mechanism explaining the myocardial damage, histological examination of lymphatic nodes might be of interest, as Röltgen et al. described altered germinal center architecture following COVID-19 vaccination [30]. This aspect could not be addressed in our analysis, as systematic lymph node sampling was not part of our standardized autopsy protocol.

Finally, we cannot provide a definitive functional proof or a direct causal link between vaccination and myocarditis. Further studies and extended registry are needed to identify persons at risk for this potentially fatal AEFI and may be aided by detailed clinical, serological, and molecular analyses which were beyond the scope of this study. Considering that this fatal adverse event may affect healthy individuals, such registry and surveillance programs may improve early diagnosis, close monitoring, and treatment.


Original Article: