ESC HEART FAILURE REVIEW

ESC Heart Failure (2024)

Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.14680

Autopsy findings in cases of fatal COVID-19 vaccine-

induced myocarditis
Nicolas Hulscher1* , Roger Hodkinson2, William Makis2,3 and Peter A. McCullough2,4,5
1
University of Michigan School of Public Health, Ann Arbor, MI, USA; 2The Wellness Company, Boca Raton, FL, USA; 3Cross Cancer Institute, Alberta Health Services,
Edmonton, Canada; 4Truth for Health Foundation, Tucson, AZ, USA; and 5McCullough Foundation, Dallas, TX, USA

Abstract
COVID-19 vaccines have been linked to myocarditis, which, in some circumstances, can be fatal. This systematic review aims to
investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. We per-
formed a systematic review of all published autopsy reports involving COVID-19 vaccination-induced myocarditis through 3
July 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included.
Causality in each case was assessed by three independent physicians with cardiac pathology experience and expertise. We ini-
tially identified 1691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases.
The cardiovascular system was the only organ system affected in 26 cases. In two cases, myocarditis was characterized as a
consequence from multisystem inflammatory syndrome. The mean age of death was 44.4 years old. The mean and median
number of days from last COVID-19 vaccination until death were 6.2 and 3 days, respectively. We established that all 28 deaths
were most likely causally linked to COVID-19 vaccination by independent review of the clinical information presented in each
paper. The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19
vaccine-induced myocarditis, its pathobiological mechanisms, and related excess death, complemented with autopsy
confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine
myocarditis, suggests that there is a high likelihood of a causal link between COVID-19 vaccines and death from myocarditis.

Keywords Myocarditis; Sudden death; Autopsy; COVID-19; COVID-19 vaccines; mRNA; SARS-CoV-2 vaccination
Received: 9 November 2023; Accepted: 28 December 2023
*Correspondence to: Nicolas Hulscher, University of Michigan School of Public Health, Ann Arbor, MI, USA. Email: [email protected]
A previous iteration of this manuscript was posted on the Preprints.org preprint server on 18 July 2023.

Introduction Moderna—mRNA-1273), viral vector (AstraZeneca—ChAdOx1

nCoV-19, Johnson & Johnson—Ad26.COV2.S, and Sputnik V),
As of 6 July 2023, SARS-CoV-2 has infected ~767 726 861 in- and protein subunit (Novavax—NVX-CoV2373 and Zifivax—
dividuals around the world, causing 6 948 764 deaths.1 The ZF2001).3 mRNA and viral vector vaccines involve the bodily
US government, in reaction to the pandemic, implemented synthesis of the SARS-CoV-2 Spike protein as the foundation
the Operation Warp Speed (OWS) initiative. This resulted in of the immune response, while protein subunit vaccines
the development and administration of the first doses of utilize injection of exogenous Spike protein, bypassing the
COVID-19 vaccine in <11 months after the identification of need for genetic mechanisms.3 Regardless of the vaccine
the SARS-CoV-2 genetic sequence.2 This marked the most platform used, circulating SARS-CoV-2 Spike protein is the
rapid development of a vaccine in history; however, there likely detrimental agent through which COVID-19 vaccines
was insufficient time and investigation to adequately estab- cause biological harm.4–13 Spike protein can initiate the
lish cardiovascular safety.2 At the time of writing, ~70% of breakdown and internalization of angiotensin-converting
the world population have been vaccinated with at least enzyme 2 (ACE2) receptors, which may disrupt the renin–
one dose of a COVID-19 vaccine.1 angiotensin system (RAS) and lead to increased inflammation,
The predominant COVID-19 vaccine platforms include vasoconstriction, and thrombosis.4 Further, Spike protein can
messenger RNA (mRNA) (Pfizer–BioNTech—BNT162b2 and stimulate platelets and inflict damage to the endothelium,

© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,
provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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2 N. Hulscher et al.

which can lead to arterial and venous thrombosis.5 Immune as 2.3% and 2.8%, respectively. Because of the frequent oc-
cells that have absorbed the lipid nanoparticles (LNPs) currence of this problem in cardiovascular practice, the
subsequently reintroduce them into the bloodstream with a United Kingdom20 and Australia21 have issued clinical prac-
higher number of exosomes carrying microRNAs and Spike tice guidelines on the diagnosis and management of COVID-
protein, possibly resulting in drastic inflammation.5 19 vaccine-induced myocarditis.
Long-term immune surveillance may be compromised by Up to 16 June 2023, the Vaccine Adverse Event Reporting
mRNA COVID-19 vaccines due to IRF7, IRF9, p53, and BRCA System (VAERS) included 1 569 668 adverse event reports as-
suppression.5,6 There is a high probability of a causal link sociated with COVID-19 vaccines, including 35 487 deaths,
between COVID-19 mRNA vaccination and myocarditis, 27 229 myocarditis and pericarditis, and 20 184 heart attack
neurodegenerative disease, immune thrombocytopenia, reports.22 Before the COVID-19 pandemic, Meissner reported
Bell’s palsy, liver disease, impaired adaptive immunity, that 86% of VAERS entries were completed by medical per-
impeded DNA damage response, and tumourigenesis.5 More- sonnel or vaccine manufacturers and only 14% were made
over, a recent study found that repeated COVID-19 vaccina- by the patient or their family.23 Thus, VAERS has demon-
tion with mRNA-based vaccines leads to the production of strated a very strong crude signal for myocarditis as an
abnormally high concentrations of immunoglobulin G4 accepted complication of COVID-19 vaccination; however, ad-
(IgG4) antibodies.7 These antibodies can fail to neutralize ditional information can be gleaned from autopsy in cases of
Spike protein, which has been shown to circulate for at least death that are suspected to be caused by COVID-19 immuni-
28 days, cause immune suppression, and promote the devel- zation. In fact, Walach et al. stated that all deaths after
opment of autoimmune diseases including myocarditis.7–13 COVID-19 vaccination should be investigated with an autopsy
In June 2021, the US Food and Drug Administration (FDA) to better our understanding of the vaccines deleterious
and Centers for Disease Control and Prevention (CDC) issued mechanisms on the human body.24 Autopsies represent one
a joint warning on myocarditis occurring after mRNA of the most powerful diagnostic methods in medicine, ascer-
COVID-19 vaccination.14 A PubMed search performed at the taining causes of death and elucidating the pathophysiologi-
time of writing for ‘myocarditis’ and ‘COVID-19 vaccination’ cal mechanisms of disease.25 COVID-19 vaccines exhibit
yielded 994 results, indicating extensive interest in COVID- multiple mechanisms of injury to the cardiovascular system
19 vaccine-induced myocarditis among researchers. Rose and are associated with a considerable number of adverse
and McCullough found that the peak age was 18–24 years event reports, thus representing an exposure that may be
and 90% of cases were men.15 Myocarditis development causally linked to death in some myocarditis cases. This
most commonly occurred after the second dose; however, systematic review aims to investigate potential causal links
additional cases occurred after the third dose, adding to between COVID-19 vaccines and death from myocarditis
the cumulative risk for individuals continuing with every using post-mortem analysis.
6 month injection schedules.15 Avolio et al. demonstrated
the cardiac pericyte as one of the several cell lines that take
up mRNA, produce Spike protein, and express it on the cell Methods
surface inciting autoimmune attack.13 Yonker et al. found
that children hospitalized with myocarditis had presence of Data sources and search strategy
free Spike protein not neutralized by antibodies while those
who were asymptomatic had appropriate neutralization of We conducted a systematic review of all published autopsy
Spike protein by anti-Spike antibodies.11 A biodistribution reports involving COVID-19 vaccination-induced myocarditis
study has shown that LNPs can travel to the heart as well through 3 July 2023. We searched PubMed and ScienceDirect
as other vital organs.16 Baumeier et al. found that among using all possible combinations of the following keywords:
15 young individuals suffering from myocarditis who ‘COVID-19 Vaccine’, ‘SARS-CoV-2 Vaccine’, or ‘COVID Vaccina-
underwent cardiac biopsy, the myocardium stained for tion’, and ‘Post-mortem’, ‘Autopsy’, or ‘myocarditis’. No
SARS-CoV-2 Spike protein and not nucleocapsid, effectively language restrictions were applied to the search. All included
ruling out infection and leaving vaccination as the only possi- studies were examined for pertinent literature contained in
ble source of Spike protein.17 Furthermore, they found a their references.
range of pathologies from inflammatory cardiomyopathy to
active myocarditis and severe giant cell myocarditis.17 Detec-
tion of Spike protein and CD4+ T-cell-dominated inflamma- Eligibility criteria and selection process
tion within cardiac tissue suggested vaccine-triggered
autoimmune processes.17 Two prospective cohort studies, The following inclusion criteria were used: all autopsy studies
by Mansanguan et al.18 and Buergin et al.,19 suggested that (original articles, case reports, and case series in any
the incidence of myocarditis or troponin elevation from language) that include COVID-19 vaccine-induced myocarditis
COVID-19 vaccine dose numbers 2 and 3 could be as high as a possible cause of death. Exclusion criteria included

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Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis 3

articles with no reported vaccination status, articles with no fected in 26 cases. In two cases, myocarditis was seen as a
autopsy results, papers without any myocarditis cases, animal consequence from multisystem inflammatory syndrome
studies, review articles, systematic reviews, and meta- (MIS) (Figure 2). The number of days from vaccination to
analyses. Two authors (NH and PAM) independently re- death was 6.2 (mean) and 3 (median). Most (75%) of the
viewed the entirety of the studies retrieved to determine deaths occurred within a week from last vaccination
their eligibility for inclusion and removed any ineligible or du- (Figure 3).
plicate studies. In cases where there were disagreements All 28 cases (100%) were found to have a high likelihood of
about including an article, the two authors engaged in a dis- being causally linked to COVID-19 vaccination in accordance
cussion until a consensus was achieved. with independent adjudication. Most cases had symptoms
consistent with myocarditis prior to death (chest pain and ef-
fort intolerance), and in the case of Choi et al., a 22-year-old
Data extraction and analysis Korean man died in the hospital after 7 h of intensive at-
tempts at supportive care.33 The autopsy showed intense in-
Two authors (NH and PAM) independently extracted all indi- flammation and destruction of cardiac tissue including the
vidual case data (age, sex, vaccine type, dose number, period conduction system. Other cases had no reported symptoms
from last vaccine administration to death, and post-mortem before death. Gill et al. reported two boys, age 16 and 17,
findings) from the included studies into Microsoft Excel. If who died a few days after mRNA injection while asleep at
the data extracted from the included studies were not iden- home.31 The case reported by Takahashi et al. demonstrated
tical between the two authors, discussion and re-extraction that the proximal cause of death was an aortic dissection
of the data were employed until a consensus was reached. with coincident epicardial myocarditis, both of which were
Descriptive statistics were calculated using all available data. determined related to vaccination.28 Suzuki et al. reported a
In the calculation of mean age, estimated age values were series of 54 cases of which 3 are included in our analysis
excluded. Causality in each case was assessed in accordance based on the findings of suspected concurrent myocarditis
with independent review by three qualified physicians with in cases with or without coincident coronary artery disease
experience and expertise in cardiac pathology (PAM, RH, and ischaemic cardiomyopathy.30 Autopsies revealed patchy
and WM). A quorum of two out of three was required to inflammation suggesting that sudden arrhythmic death could
establish a highly probable causal link to COVID-19 vaccina- have occurred due to a re-entrant ventricular arrhythmia
tion. If this consensus was not reached, no causal link to culminating in sudden cardiac death. The authors in these
vaccination could be made. The adjudicators used all avail- cases concluded that the cause of death was COVID-19
able evidence (demographic information, clinical vignette, vaccine-induced myocarditis.
vaccination information, and post-mortem findings) and
assessed any temporal relationships, the strength of evi-
dence and their consistency with well-described COVID-19
vaccine-induced myocarditis characteristics and mechanisms, Discussion
and possible alternate causes of death to evaluate causal
links. We established that all 28 deaths were most likely causally
linked to COVID-19 vaccination by independent review of
the clinical information presented in each paper. Our data
Results are consistent with the overall epidemiological literature
[PubMed search for (COVID-19 vaccination) * (myocarditis)
The database search yielded 1691 studies that may have met = 994 papers] concerning COVID-19 vaccine-induced myocar-
our inclusion criterion. After removing 1212 duplicate papers ditis where the Bradford Hill criteria40 support causality from
and screening 479 unique studies, only 12 met our inclusion an epidemiological perspective. This includes biological plau-
criterion. A detailed screening of references found eight addi- sibility, temporal association, internal and external validity,
tional papers, with two of them fulfilling our inclusion crite- coherence, analogy, and reproducibility with each successive
rion. Overall, we included 14 studies that contain 28 autopsy report of myocarditis-related death after COVID-19 vaccina-
cases of COVID-19 vaccinees diagnosed with myocarditis tion. Baumeier et al.’s findings that the myocardium stained
(Figure 1). for SARS-CoV-2 Spike protein and not nucleocapsid among
The included 14 reports26–39 are summarized in Table 1. Of 15 young individuals suffering from myocarditis indicated
the 28 autopsy cases, 9 (32.1%) were female. The mean age that the sole cause of cardiac injury in post-vaccine myocardi-
of death was 44.4 years old. Eighteen cases (64%) received tis is highly likely to be COVID-19 vaccination, confirming our
Pfizer–BioNTech vaccines, nine cases (32%) received results (Figure 4).17 In addition, Baumeier et al. found Spike
Moderna vaccines, and one case received a Zifivax vaccine. protein and CD4+ T-cell-dominated inflammation, suggesting
The cardiovascular system was the only organ system af- the COVID-19 vaccine as the single cause of autoimmune

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4 N. Hulscher et al.

Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram detailing the study selection process.

reaction processes seen in myocardial histology (Figure 5).17 where there is no other explanation. COVID-19 vaccine Spike
COVID-19 vaccination and SARS-CoV-2 infection before or protein is produced in the body for an uncontrolled duration
after one or more vaccine administrations may have contrib- and in unknown quantity resulting in deleterious effects,4–13
uted to cardiac Spike protein injury and inflammation in cases especially on the heart,10,11,13–21 explaining the cardiovascu-
where infection was not ruled out. The predominant lar deaths seen in our study without evidence of other organ
mechanism of death is most likely a sudden arrhythmia such system involvement. MIS has been identified following
as ventricular tachycardia or ventricular fibrillation. Relatively COVID-19 vaccination in both children44 and adults45; how-
few cases had antecedent fulminant pump failure. These ever, we found only two autopsy cases with this diagnosis.
data are concerning when considered in light of young indi- MIS may be caused by the systemic distribution of the LNPs
viduals, particularly male athletes who have had sudden containing mRNA after vaccine administration16 and conse-
death after vaccination without an autopsy. Polykretis and quent systemic Spike protein expression on cell surfaces that
McCullough have reported that, among professional and results in extensive inflammation. Considering the average
semi-professional European athletes <35 years old, com- time of 6.2 days between vaccination and death, a temporal
pared with a stable period before the pandemic, the annual- link between COVID-19 vaccination and death is corroborated
ized rate of sudden death since the rollout of COVID-19 by the observation that SARS-CoV-2 mRNA Spike vaccine
vaccines has increased 10-fold.41 Cadegiani has postulated sequences can persist in the bloodstream for at least 28 days
that a surge of catecholamines can be the trigger for after vaccination.12
COVID-19 vaccine-induced sudden death,42 which could ex- Ittiwut et al. have found that genetic susceptibility to
plain the occurrence during exercise and sports as well as sudden death may explain some of the variation.46 Polymor-
during the early morning waking hours from sleep where phisms in the SCN5A channel were associated with the
there is a surge of epinephrine and norepinephrine.43 highest rates of sudden death in their study.46 The over-
Our findings escalate concerns regarding COVID-19 whelming predominance of men among COVID-19 vaccine-
vaccine-induced myocarditis and its mechanisms, particularly induced myocarditis cases15 and with other vaccines
in cases of sudden unexpected death in younger individuals including smallpox and influenza47 suggests that androgen

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DOI: 10.1002/ehf2.14680
 Table 1 Case information from all included studies of autopsy-confirmed COVID-19 vaccine-induced myocarditis
a b
Author Case Age Sex Vaccine Dose Disease Period Post-mortem findings
26
Nushida, 2023 (Japan) 1 14 F Pfizer 3 MIS, myopericarditis 2 days Congestive oedema of the lungs, T-cell lymphocytic and
macrophage infiltration in the lungs, pericardium, and
myocardium of the left atria and left ventricle, liver,
kidneys, stomach, duodenum, bladder, and diaphragm.
The presence of foci centred on the atria and
breathlessness are the findings that led to the diagnosis
that the cause of death was vaccine-related
myopericarditis, which led to severe arrhythmias and
progressive heart failure.
27
Mörz, 2022 (Germany) 1 76 M Pfizer 2 Encephalitis, myocarditis 21 days Signs of aspiration pneumonia and systemic
arteriosclerosis were evident. Brain examination
uncovered acute vasculitis (predominantly lymphocytic)
as well as multifocal necrotizing encephalitis of
unknown aetiology with pronounced inflammation
including glial and lymphocytic reaction. In the heart,
signs of chronic cardiomyopathy as well as mild acute
lympho-histiocytic myocarditis and vasculitis were
present. Only Spike protein but no nucleocapsid protein
could be detected within the foci of inflammation in
both the brain and the heart. Also, mild acute splenitis,
gastric mucosal bleeding, liver lipofuscinosis, and mild
active nephritis were found.
28
Takahashi, 2022 (Japan) 1 ‘90s’ M Pfizer 3 Pericarditis 14 days Dissection of the ascending aorta and pericardial
hemotamponade. The heart showed a white villous
Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis

surface, and the pericardium was fibrously thick.

Microscopic examination revealed pericarditis with
predominantly macrophage and lymphocyte infiltration.
29
Satomi, 2022 (Japan) 1 61 F Pfizer 1 Myocarditis 10 days The heart showed moderate dilatation of both ventricles,
and the myocardium showed an uneven colour change
and decreased elasticity. Histologically, severe
myocarditis with extensive myocytolysis was observed.
The myocarditis showed severe inflammatory cell
infiltration with T-lymphocyte and macrophage
predominance, and vast nuclear dust accompanying
neutrophilic infiltration was observed. In the bone
marrow and lymph nodes, hemophagocytosis was
observed. SARS-CoV-2 nucleic acids were not detected
using multivirus real-time PCR system.
30
Suzuki, 2021 (Japan) 1 91 M Moderna 1 Ischaemic heart disease, myocarditis 6 days Old myocardial infarction in the post-lateral wall, severe
coronary artery sclerosis, leucocyte and lymphocyte
infiltration in the left anterior wall, diabetic
nephropathy, and aortic sclerosis.
2 24 M Moderna 2 Myocarditis 3 days Scattered necrosis and fibrosis of cardiomyocytes with a
perivascular pattern of inflammatory cell infiltration
(consisting of predominantly lymphocytes).
3 39 M Moderna 2 Myocarditis 3 days Scattered inflammatory cell infiltration (consisting of
predominantly monocytes) in the interstitial space of
cardiomyocytes/around the coronary arteries, interstitial
(Continues)

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Table 1 (continued)
a b
Author Case Age Sex Vaccine Dose Disease Period Post-mortem findings
oedema, eosinophilic and wavy change of
cardiomyocytes, lung oedema, and coronary sclerosis.
31
Gill, 2022 (USA) 1 ‘Teenage’ M Pfizer 2 Myocarditis 3 days No molecular evidence of SARS-CoV-2 infection. Global
myocardial injury with areas of coagulative myocytolysis
and contraction bands, with a perivascular pattern of
inflammation consisting of mainly neutrophils and
histiocytes, scant lymphocytes, and occasional
eosinophils. No acute or organizing thrombi were
detected. Pattern of injury is consistent with stress
cardiomyopathy.
2 ‘Teenage’ M Pfizer 2 Myocarditis 4 days No molecular evidence of SARS-CoV-2 infection. As with
the previous case, global myocardial injury was found
but with more widespread transmural ischaemic
changes and more interstitial inflammation.
Subepicardial distribution of injury was not seen. No
acute or organizing thrombi were detected.
32
Ameratunga, 2022 (New Zealand) 1 57 F Pfizer 1 Myocarditis 3 days Left pleural mass originating from the mediastinum was
found. Multifocal inflammatory cell infiltration in the
myocardium and areas of eosinophil-rich inflammatory
aggregates with myocyte necrosis were found. An
abundant eosinophilic infiltrate with myocyte necrosis
was observed. Antibodies to SARS-CoV-2 were not
detected.
33
Choi, 2021 (Korea) 1 22 M Pfizer 1 Myocarditis 5 days Histological examination of the heart showed isolated
atrial myocarditis, with neutrophil and histiocyte
predominance. Immunohistochemical C4d staining
showed scattered single-cell necrosis of myocytes, which
was not accompanied by inflammatory infiltrates.
Extensive contraction band necrosis was seen in the atria
and ventricles. There was no evidence of
microthrombosis or infection in the heart and other
organs.
34
Schneider, 2021 (Germany) 1 65 M Pfizer 1 Myocarditis 1 day Severe coronary sclerosis, massive cardiac hypertrophy,
myocardial infarction scars, myocarditis, and anaphylaxis
diagnostics negative.
35
Verma, 2021 (USA) 1 42 M Moderna 2 Myocarditis ~14 days Autopsy revealed biventricular myocarditis. An
inflammatory infiltrate admixed with macrophages, T
cells, eosinophils, and B cells was also observed.
36
Schwab, 2023 (Germany) 1 46 M Pfizer 1 Myocarditis 0 days Histological examination showed inflammatory
infiltration of the myocardium. The infiltrate was focal
and interstitial. It was predominantly detected in
sections taken from the RV wall and interventricular
septum. The histological and immunohistochemical
characterization revealed that the inflammatory infiltrate
was predominantly composed of lymphocytes.
Microfocal myocyte injury was demonstrable. Lacked
pre-existing, clinically relevant heart disease.
(Continues)

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 Table 1 (continued)
a b
Author Case Age Sex Vaccine Dose Disease Period Post-mortem findings
2 50 F Moderna 1 Myocarditis 1 day Histological examination showed inflammatory
infiltration of the myocardium. The infiltrate was focal
and interstitial. It was predominantly detected in
sections taken from the RV wall and interventricular
septum. The histological and immunohistochemical
characterization revealed that the inflammatory infiltrate
was predominantly composed of lymphocytes.
Microfocal myocyte injury was demonstrable. An
inflammatory infiltration of the epicardium and the
subepicardial fat tissue was concomitantly found.
Lacked pre-existing, clinically relevant heart disease.
3 62 F Pfizer 1 Myocarditis 7 days Histological examination showed inflammatory
infiltration of the myocardium. The infiltrate was focal
and interstitial. It was predominantly detected in
sections taken from the RV wall and interventricular
septum. The histological and immunohistochemical
characterization revealed that the inflammatory infiltrate
was predominantly composed of lymphocytes.
Microfocal myocyte injury was demonstrable. An
inflammatory infiltration of the epicardium and the
subepicardial fat tissue was concomitantly found.
Lacked pre-existing, clinically relevant heart disease.
Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis

4 55 M Pfizer 2 Myocarditis 4 days Histological examination showed inflammatory

infiltration of the myocardium. The infiltrate was focal
and interstitial. It was predominantly detected in
sections taken from the RV wall and interventricular
septum. The histological and immunohistochemical
characterization revealed that the inflammatory infiltrate
was predominantly composed of lymphocytes. An
inflammatory infiltration of the epicardium and the
subepicardial fat tissue was concomitantly found.
Lacked pre-existing, clinically relevant heart disease.
5 75 F Pfizer 1 Myocarditis 1 day Histological examination showed inflammatory
infiltration of the myocardium. The infiltrate was focal
and interstitial. It was predominantly detected in
sections taken from the RV wall and interventricular
septum. The histological and immunohistochemical
characterization revealed that the inflammatory infiltrate
was predominantly composed of lymphocytes. An
inflammatory infiltration of the epicardium and the
subepicardial fat tissue was concomitantly found.
Lacked pre-existing, clinically relevant heart disease.
Analysis for potential infectious agents causing a
myocarditis revealed low viral copy numbers of human
herpes virus 6.
(Continues)

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 8

Table 1 (continued)
a b
Author Case Age Sex Vaccine Dose Disease Period Post-mortem findings
37
Hoshino, 2022 (Japan) 1 27 M Moderna 1 Myocarditis 36 days An autopsy revealed asymmetric LV hypertrophy,
thickening of the RV wall (550 g; LV wall, 11–16 mm; RV
wall, 5–7 mm), myxomatous degeneration of the
posterior leaflet of the mitral valve, and hypertrophy of
the posteromedial papillary muscle. Microscopic findings
revealed that cardiac myocytolysis and widespread
fibrosis were observed, and significant mixed
inflammatory infiltration (T cells, macrophages, and
eosinophils) was observed in the LV free wall and the
anterior portion of the ventricular septum.
38
Dong, 2022 (China) 1 34 F Zifivax 1 Myocarditis 12 days Autopsy showed severe interstitial myocarditis, including
multiple patchy infiltrations of lymphocytes and
monocytes in the myocardium of the LV and RV walls
associated with myocyte degeneration and necrosis.
39
Cho, 2023 (Korea) 1 22 M Pfizer 1 SCD from myocarditis 6 days Diffuse inflammatory infiltration, with neutrophil and
histiocyte predominance in both atria and near AV node
and SA node. Free of inflammatory infiltrates in
ventricular myocardium.
2 30 F Pfizer 1 SCD from myocarditis 3 days Diffuse inflammatory cell infiltration, myocardial fibre
disarray, interstitial fibrosis, and localized necrosis of
myocyte.
3 45 M Pfizer 2 SCD from myocarditis 3 days Localized infiltration of neutrophils, lymphocytes,
histiocyte, and a few eosinophils was noted. A small
number of cardiomyocyte necroses were also seen.
4 25 M Pfizer 2 SCD from myocarditis 3 days Autopsy revealed myocarditis.
5 45 M Pfizer 2 SCD from myocarditis 3 days Interstitial infiltration of various inflammatory cells
including lymphocyte, neutrophil, eosinophil, and focal
necrosis suggesting the diagnosis of myocarditis.
6 36 F Moderna 1 SCD from myocarditis 2 days Neutrophil, eosinophil, and histiocyte infiltration in the
myocardium suggesting acute myocarditis.
7 33 M Moderna 2 SCD from myocarditis 1 day Multiple focal infiltrations of acute inflammatory cells
and chronic inflammatory cells in the myocardium.
8 33 M Moderna 2 SCD from myocarditis 3 days Various inflammatory cells such as neutrophils,
eosinophils, lymphocytes, macrophages, and
cardiomyocyte necrosis in the myocardial interstitium
and epicardium suggested myocarditis.
AV, atrioventricular; LV, left ventricular; MIS, multisystem inflammatory syndrome; RV, right ventricular; SA, sinoatrial; SCD, sudden cardiac death.
‘~’ indicates inferred period (estimated period using all available information).
a
Dose = total number of vaccine doses received.
b
Period = days from most recent vaccine administration to death.

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9

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Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis

Figure 3 Distribution of time from last vaccine administration to death.

Figure 2 Proportion of cases by affected organ system.
 20555822, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14680 by Cochrane Portugal, Wiley Online Library on [18/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
10 N. Hulscher et al.

Figure 4 Evidence of SARS-CoV-2 Spike protein in cardiac tissue after COVID-19 vaccination. Representative immunohistochemical stainings of SARS-
CoV-2 Spike protein in endomyocardial biopsies from patients diagnosed with inflammatory dilated cardiomyopathy (DCMi) after receiving Comirnaty®
[(A, B) Patients 5 and 10] or Vaxzevria® [(C) Patient 13]. (D) SARS-CoV-2-positive cardiac tissue served as positive control. Magnification ×400. Scale
17
bars: 20 m. Figure and legend reprinted from Baumeier et al. Permission to use this figure has been granted in accordance with the open access
Creative Commons CC BY 4.0 licence.

+
Figure 5 Inflammatory cardiomyopathy in response to COVID-19 vaccination is dominated by CD4 T cells. Representative immunohistochemical
+ +
stainings of CD4 and CD8 T cells in endomyocardial biopsies from patients diagnosed for inflammatory dilated cardiomyopathy (DCMi) after receiving
Comirnaty® [(A, B) Patients 6 and 10] or Vaxzevria® [(C) Patient 13] vaccines, respectively. Magnification ×400. Scale bars: 20 m. Figure and legend
17
reprinted from Baumeier et al. Permission to use this figure has been granted in accordance with the open access Creative Commons CC BY 4.0
licence.

receptors or some other undiscovered interaction with male Figure 6 highlights the major steps in COVID-19 vaccine-
hormones may play a role in the manifestation of induced myocarditis. Baseline susceptibility includes male
vaccine-induced myocarditis. gender, age 18–24, SCN5A polymorphisms, and athletic

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Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis 11

Figure 6 COVID-19 vaccine-induced myocarditis characteristics.

tendency with surges of catecholamines in routine sports ac- tected, risks include sudden cardiac death during sports or
tivities and during sleep. Some batches/vials of mRNA may sleep where ~65% cannot be resuscitated41 and are classified
have more concentrated LNP–mRNA complexes or cDNA con- as sudden adult death syndrome (SADS). In such cases, it is
taminants as suggested by Schmeling et al., who found that important to document the brand, number of doses, inocula-
~4.2% of vials are responsible for >70% of serious adverse tion dates, lot numbers, and, as our data indicate, procure-
events.48 The LNPs loaded with mRNA are known to system- ment of an autopsy.
ically circulate for 28 days or more; thus, there are many cy- Vaccines have played an important role in the advance-
cles of coronary flow and cardiac uptake of the LNP–mRNA ment of immunology, leading to strategies of prevention,
complex.12,49 These data indicate that the mRNA sequences and lessening the burden of infectious diseases. Vaccines,
are long-lasting and durable within pericytes, cardiomyo- while preventative, may fail as treatment to end pandemics
cytes, and other cell lines, providing the genetic instructions with highly prevalent infections.51 Some immunizations as
for the continuous production of Spike protein, which is we have learned, including the COVID-19 vaccine, can have
expressed on cell surfaces and in the interstitial space, which significant side effects. Myocarditis may be a significant con-
can incite a deleterious autoimmune reaction. According to tributor to overall deaths observed after COVID-19 vaccina-
Mansanguan et al., 57% of myocarditis cases may be tion. The studies analysed in this review are consistent with
asymptomatic.18 Among those with symptoms, >90% are multiple studies that show excess mortality after vaccination,
hospitalized with clinical and diagnostic features including which may have occurred due to myocarditis that was not de-
chest pain, heart failure, electrocardiogram (ECG) changes, tected before sudden death. Pantazatos and Seligmann re-
positive troponin levels, and cardiac MRI imaging demon- ported that all-cause mortality increased in most age groups
strating patchy late gadolinium enhancement.50 If unde- up to 5 weeks after vaccination resulting in 146 000 to

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12 N. Hulscher et al.

187 000 vaccine-associated deaths in the United States by topsies, to provide the medical community with a more com-
August 2021.52 Skidmore elucidated that 278 000 Americans prehensive understanding of fatal COVID-19 vaccine-induced
may have died from the COVID-19 vaccine by December myocarditis. The temporal relationship, internal and external
2021.53 These findings were corroborated by Aarstad and consistency seen among cases in this review with known
Kvitastein, who reported that, among European countries, a COVID-19 vaccine-induced myocarditis, its pathobiological
higher COVID-19 vaccine uptake in 2021 was associated with mechanisms, and related excess death, complemented with
increased all-cause mortality in the first 9 months of 2022 af- autopsy confirmation, independent adjudication, and applica-
ter accounting for alternative explanations.54 Excess deaths tion of the Bradford Hill criteria to the overall epidemiology
not caused by COVID-19 have been identified worldwide af- of vaccine myocarditis, suggests that there is a high likelihood
ter the mass COVID-19 vaccination programmes began,55–60 of a causal link between COVID-19 vaccines and death from
indicating the presence of a novel detrimental exposure myocarditis. This may also apply to some cases where sud-
among populations. Pantazatos and Seligmann extrapolated den, unexpected death has occurred in a vaccinated person.
that VAERS reports are underreported by a factor of 20.52 If the COVID-19 vaccines remain on the market for public
When this factor is applied to the 16 June 2023 VAERS death use, urgent investigation is required for the purpose of
report count of 35 487,22 the number of deaths in the United risk stratification and mitigation in order to reduce the
States and other countries that use VAERS becomes 709 740. population occurrence of fatal COVID-19 vaccine-induced
Please note that this extrapolation is a general estimate and myocarditis.
may not be accurate. Nonetheless, if the sizeable number of
fatalities was to be confirmed, the COVID-19 vaccines would
constitute the largest biological safety disaster in human Conflict of interest
history.
Our paper has all the limitations of small sample sizes R.H., W.M., and P.A.M. are either affiliated with or receive
derived from assembling case reports or series. These include salary support (modest) or equity (modest) in The Wellness
selection bias of cases for autopsy, publication bias against Company, which had no role in the study.
disclosing more cases from academic medical centres and
medical examiners for fear of reprisal, and unknown con-
founders such as undetected cardiotropic pathogens, alcohol
abuse, and drug abuse, which are all threats to validity. Funding
In summary, we identified a series of myocarditis-related
deaths following COVID-19 vaccination, confirmed with au- No funding was received for conducting this study.

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