Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24SEP1097

Post-Vaccine Myocarditis: Clinical Insights and

Epidemiological Trends
Dr. N. Meher Satya Vani
Pharm.D
Assistant Professor (Dept. of Pharmacy Practice)
GIET School of Pharmacy, Rajahmundry, 533296, Andhra Pradesh, India

Abstract:- Myocarditis is a rare but key adverse event with acute COVID-19 or other viral infections. Notably,
linked to mRNA COVID-19 vaccines, predominantly in natural killer cells were elevated, autoantibodies to specific
young males. Epidemiological data indicate an incidence self-antigens were reduced, and one case tested positive on a
of approximately 12.6 cases per million doses heart disease gene panel [3].
administered to patients aged 12-39 years, mostly
following the second dose of the vaccine. Most patients Experimental hypotheses explaining vaccine-
present with elevated levels of cardiac biomarkers, chest associated myocarditis include molecular mimicry between
pain, and abnormal ECG findings within a few days of the SARS-CoV-2 spike protein and self-antigens, the
vaccination. Proposed mechanisms for the exact triggering of immunologic pathways, immune responses to
pathophysiology of this include molecular mimicry mRNA, and cytokine expression dysfunction. It remains
between the SARS-CoV-2 spike protein and cardiac unclear why males are more frequently affected than
antigens, activation of immune pathways, and females, although several theories have been proposed. For
dysregulated cytokine expression. Despite these findings, instance, men may be more likely to be diagnosed with heart
the overall benefit-risk balance for COVID-19 conditions than women, and differences in sex hormones
vaccination remains positive, as the majority of patients may influence immune responses, potentially contributing to
recover fully. In contrast, COVID-19-associated myocarditis. However, despite these occasional occurrences
myocarditis is more common and more severe, with an of myocarditis, most patients experienced improvement in
estimated incidence of 1,000-1,400 cases per 100,000 imaging and diagnostic markers, as well as resolution of
infections. Clinical presentation of vaccine-associated symptoms, with or without treatment. The benefit-risk
myocarditis is usually mild and self-limiting, and most analysis of COVID-19 vaccination demonstrates a favorable
patients do recover without significant long-term effects. balance for all age and gender groups, even with the
Treatment is usually supportive in nature and has an occasional occurrence of myocarditis. Therefore, we
emphasis on ruling out acute coronary syndrome and recommend vaccination for all individuals aged 12 years
symptomatic management for heart failure or and older [4].
arrhythmias if present. Given its low incidence and the
generally good outcome, vaccination against COVID-19 II. EPIDEMIOLOGY OF MYOCARDITIS AFTER
is recommended from 12 years of age and above, with COVID-19 VACCINATIONS
provision for ongoing surveillance for monitoring and
management of rare adverse events like myocarditis. Before the emergence of COVID-19, the Global
Burden of Cardiovascular Disease reported an annual
Keywords:- Myocarditis, COVID-19, Vaccination, mRNA prevalence of myocarditis cases at 6.1 per 100,000 persons
Vaccine. aged 35-39 for men and 0.1 per 100,000 for women, with
corresponding mortality rates of 0.2 and 0.1 per 100,000,
I. INTRODUCTION respectively [5]. However, during the first eight months of
the pandemic, the incidence of excess cardiovascular deaths
Myocarditis is a rare but serious complication in England and Wales rose to 12 per 100,000, accompanied
associated with COVID-19 mRNA vaccines, primarily by an 8% increase in acute cardiovascular disease mortality
affecting young male adults and adolescents. According to in England [6]. Simultaneously, the United States
the US Centers for Disease Control and Prevention, the experienced a higher incidence of ischemic and hypertensive
incidence of myocarditis and pericarditis in individuals aged heart disease during the first 10 months of the COVID-19
12-39 is approximately 12.6 cases per million doses of the pandemic compared to the previous year [7]. A study
second mRNA vaccine dose [1,2]. In reported cases, patients published in February 2020 examining sex differences in
commonly presented with elevated cardiac troponin levels myocarditis presentation found that young individuals
and chest pain, with the majority of myocarditis cases (average age: 40 ± 17 for women and 40 ± 16 for men)
diagnosed 2-3 days after the second dose of the mRNA accounted for the majority of myocarditis cases (82%) [8].
vaccine. Cardiac MRI confirmed myocarditis in all
evaluated patients, while the remainder showed abnormal
ECGs with ST elevations. None of the cases were associated

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Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24SEP1097

Myocarditis following COVID-19 vaccination appears greater (1,000-1,400 per 100,000 COVID-19 patients) than
to be rare, with case-series studies from the United States that of vaccine-related myocarditis. Additionally, COVID-
and Israel estimating an incidence of 0.3-5.0 cases per 19-related myocarditis generally presents with more severe
100,000 vaccinated individuals. The highest prevalence symptoms and a worse prognosis compared to vaccine-
occurred after the second vaccine dose, predominantly in induced myocarditis. Among COVID-19 patients, 10% of
young males (83 of 117 patients were aged ≤30 years, and outpatients and 40% of hospitalized patients experience
only 15 were female) [9]. Most cases presented within the clinically significant myocardial injury, often in the absence
first week post-vaccination, typically 3-4 days after of myocardial infarction [11].
immunization. In cases of myocarditis unrelated to COVID-
19 or its vaccines, over 80% of patients recover The primary risk factors for cardiovascular
spontaneously. However, those hospitalized for myocarditis complications in COVID-19 patients include advanced age
face a 4-5% risk of mortality or heart transplantation within and pre-existing comorbidities such as obesity, diabetes,
the first year post-diagnosis. Conversely, up to 90% of hypertension, or renal impairment. Myocardial injury in
individuals with COVID-19 mRNA vaccine-associated these patients may result from sepsis and shock, hypoxia,
myocarditis may experience functional recovery, often after and hemodynamic instability caused by severe COVID-19
an initial episode of chest pain. To date, at least 13 deaths pneumonia, as well as direct COVID-19-mediated
have been reported as potentially linked to vaccine- microvascular injury and thrombosis. These factors can lead
associated myocarditis, though establishing a causal to elevated plasma troponin levels, ECG changes, heart
relationship is challenging due to insufficient evidence [10]. failure, and arrhythmias [12]. Characteristics of Myocarditis
associated with vaccine are listed out in table 1.
In contrast, the incidence of COVID-19-associated
myocarditis or cardiac injury is estimated to be 100 times

Table 1: Characteristics of Myocarditis Associated with COVID-19 and Post-COVID-19 mRNA Vaccination(13).
Type of Myocarditis Rate of Occurrence Survival Rate Possible Mechanisms
(%)
Viral myocarditis (common) 1 to 10 per 100,000 > 80 Genetic factors (e.g., variations in genes coding for
individuals annually sarcomeric, desmosomal, cytoskeletal, or HLA
proteins), immune cross-reactivity, sex-related
factors.
Myocarditis and cardiac 1,000 to 4,000 per 30 to 80 Microthrombosis, endothelial damage, genetic
damage associated with 100,000 SARS-CoV- factors (e.g., desmosomal, cytoskeletal,
COVID-19 2 infections sarcomeric, or HLA protein coding genes), shock,
and sepsis.
Myocarditis following COVID- 0.3 to 5.0 per > 99 Hypersensitivity reactions, genetic factors (e.g.,
19 mRNA vaccination 100,000 vaccinated variations in genes coding for sarcomeric,
individuals desmosomal, cytoskeletal, or HLA proteins),
immune cross-reactivity, sex-related factors.

III. THE PATHOPHYSIOLOGY OF B. Inflammatory Response

MYOCARDITIS IN RELATION TO THE The release of cytokines by CD4+ T-lymphocytes
COVID-19 VACCINE initiates an immunological response that is biased toward T1,
T2, T17, and T22 helper cells. B-lymphocytes also play a
The molecular and cellular pathogenesis of post-viral role in this stage by producing antibodies that contribute to
myocarditis, including that potentially triggered by the the inflammatory process [17].
COVID-19 vaccine, has been extensively studied,
particularly in animal models. The pathogenesis can be C. Variation in Outcome
summarized in a three-step process: In most cases, the immune response diminishes in the
third stage, allowing cytotoxic CD8+ T-lymphocytes to
A. Immune Initiation eliminate the virus. However, in some instances, the virus
When pathogens, typically viruses or toxins, damage may persist, leading to ongoing damage to cardiac myocytes
cardiac tissue, the innate immune system is activated, [18]. In the context of vaccine-associated myocarditis, the
exposing intracellular antigens such as cardiac myosin and inflammatory cytokines involved include TNF-α, IFN-γ, IL-
myocytes [14, 15]. During this phase, pro-inflammatory 6, and IL-1. It is hypothesized that genetic predispositions to
cytokines like interleukin-1 (IL-1) are released, and antigen- IL-6-induced inflammation could exacerbate vaccine
presenting cells (APCs) mature. Additionally, Toll-like responses [19]. Moreover, the spike protein in the vaccine
receptor 4 (TLR4) expression on macrophages is increased may lead to molecular mimicry with α-myosin, a
[16]. mechanism distinct from classic myocarditis but similar to
some COVID-19 infections [20]. This molecular mimicry
could also contribute to an autoimmune component [21].

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Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology
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IV. MECHANISM appear within a few days after the administration of a

COVID-19 vaccine, particularly in young males [24]. Most
Myocarditis induced by viruses such as human symptoms are mild and nonspecific, including subfebrile to
herpesvirus or enterovirus is typically more severe in febrile fever, shortness of breath, palpitations, lethargy, and
younger individuals and males. Genetic variants may chest discomfort or pressure, which may be dependent on
increase the risk of acute myocarditis. COVID-19 mRNA respiration [25]. However, some individuals, particularly
vaccines could potentially trigger hyperimmunity through those with minimal pericardial involvement, may not
hormonal changes, mRNA immune reactivity, and respond well to treatment. Almost all patients seeking
autoantibodies. Factors like age, sex, and immunogenetic medical assistance for vaccine-related myocarditis report
background can influence these processes. For instance, chest discomfort (95–100%), which is more frequent
testosterone associated with the COVID-19 mRNA compared to myocarditis caused by autoimmune diseases or
vaccination may affect the etiology of myocarditis [22]. viruses. This observation might result from selection bias,
where only symptomatic cases are identified [26]. Most
V. VACCINE-RELATED MYOCARDITIS: patients present elevated troponin levels, peaking 48–72
CLINICAL PRESENTATION hours after symptom onset. Inflammatory markers, such as
C-reactive protein (CRP), may be elevated when concurrent
Early diagnosis and appropriate care are crucial for pericarditis is present [27]. The signs and symptoms are
preventing the progression of vaccine-related myocarditis listed below in the table 2.
into a more serious condition [23]. Symptoms generally

Table 2: Signs and Symptoms of Myocarditis Associated with COVID-19 Vaccination.

Symptoms Signs
Chest tightness or discomfort that may depend on Increased troponins (peak 48–72 hours after symptom onset)
breathing
Breathlessness Elevated C-reactive protein (CRP)
Heart palpitations Transthoracic echocardiography shows mild pericardial effusion
Malaise Cardiac magnetic resonance imaging reveals inflammation in the heart
General weakness and fatigue Changes in electrocardiography (usually mild and nonspecific):
- Diffuse ST-segment modifications
- PQ segment depressions
- Nonspecific ST-segment modifications, sinus bradycardia
- Ventricular or supraventricular arrhythmias (very rare)
Subfebrile or febrile temperatures Severe arrhythmias and heart failure symptoms are quite rare

VI. EVALUATION AND DIAGNOSIS  Endomyocardial Biopsy: It is considered the gold

standard for the diagnosis of myocarditis, more so in
Myocarditis is often challenging to diagnose due to making a definite diagnosis of myocardial inflammation
overlapping symptoms with other clinical conditions [28]. It [31].
is crucial to maintain a high index of suspicion in cases with  (Note: CRP stands for C-reactive protein; ESR stands for
a history of viral infection, acute febrile illness, or erythrocyte sedimentation rate)
connective tissue disease [29].
VII. COMPARISON OF COVID-19 AND POST-
 Laboratory Studies: VACCINATION MYOCARDITIS
 Full Blood Count: Eosinophilia and leukocytosis in cases
of eosinophilic myocarditis. The risk of myocarditis following COVID-19 infection
 Inflammatory Markers: Elevations in Interleukins, CRP, needs to be compared with the incidence of myocarditis
and ESR. associated with mRNA vaccines. According to data from the
 Cardiac Markers: Elevated Troponin-I or Troponin-T Vaccine Adverse Event Reporting System (VAERS) and the
levels [30]. Advisory Committee on Immunization Practices as of
February 4, 2022, 164 million mRNA vaccine doses had
 Imaging and Additional Studies: been administered by January 13, 2022, with 359 cases of
 ECG : Nonspecific ST segment changes. myocarditis identified within 0 to 7 days post-vaccination.
 X-ray or Chest Radiograph: May show a pleural effusion, The Centers for Disease Control and Prevention (CDC)
pulmonary edema, vascular congestion, or nonspecific reported 146 cases of myocarditis per 100,000 COVID-19
heart enlargement. infections [32]. The risk was notably higher in males,
 Cardiac Magnetic Resonance: Shows prolonged T1 and individuals over 50, and children under 16. One study found
T2 relaxation times, which allows for presumptive that males aged 12 to 17 experienced myocarditis at a rate of
diagnosis of myocardial inflammation. approximately 450 cases per million infections [33]. This
 Coronary Angiography: Done to rule out coronary artery study involved healthcare providers serving a quarter of the
disease in a patient who has had sudden cardiac arrest. U.S. population. Following the second dose of the mRNA

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vaccine, 67 cases of myocarditis per million boys in this age preventing severe COVID-19 requiring hospitalization [34].
group were identified. The combined number of myocarditis The efficacy was reported at 98% against severe COVID-19
cases after the first and second doses was 77 cases per requiring life support and 98% against ICU admission. The
million, nearly six times lower than the rate observed study by Bettina Heidecker et al.[35] also highlighted
following COVID-19 infection. A different perspective avoided hospital stays and an excess number of myocarditis
comes from a recent study that compared vaccinated cases associated with COVID-19 vaccination, as detailed in
individuals with those who did not receive the BNT162b2 Table 3.
vaccine, finding that vaccination was highly effective in

Table 3: Avoided Hospital Stays and Excess Cases of Myocarditis Associated with COVID-19 Vaccination
Group (Age and Gender) Inpatient Stays Avoided Excess Vaccine-Associated Cases of Myocarditis
All adults (18 to 39 years)
mRNA-1273 (Moderna®) 2982 33
BNT162b2 (Pfizer-BioNTech®) 2820 24
Males 18 to 39 years
mRNA-1273 (Moderna®) 1903 68
BNT162b2 (Pfizer-BioNTech®) 1799 47

VIII. TREATMENT OF MYOCARDITIS CAUSED proposed therapy based on VAERS dataset information.
BY VACCINATIONS Patients showing signs of cardiogenic shock fall into this
category. Shared decision-making is crucial when discussing
In cases where patients present with chest pain, it is potential booster doses or additional vaccinations with
crucial to rule out acute coronary syndrome both clinically patients. Moreover, individuals with "long COVID"
and angiographically, especially when the diagnosis is syndrome (PASC) need ongoing monitoring. The link
unclear. For those experiencing heart failure with a lower between PASC and vaccination remains poorly understood,
ejection fraction, treatment options include sodium-glucose and the epidemiology of this condition is still debated.
cotransporter 2 inhibitors, beta-blockers, mineralocorticoid Additionally, discussing the benefits and risks of receiving
receptor antagonists, and either angiotensin-converting further vaccinations is important, especially with young men
enzyme inhibitors or angiotensin receptor-neprilysin who experienced myocarditis after their initial or subsequent
inhibitors [36]. Arrhythmias should be treated according to doses. Alternative vaccine platforms, such as the
guidelines specific to the type of arrhythmia. In the very rare recombinant Spike (rS) protein nanoparticle vaccine NVX-
instances of fulminant myocarditis or cardiogenic shock, CoV2373 (Novavax), have been given Emergency Use
temporary use of corticosteroids may be considered. Authorization by the FDA for unvaccinated individuals aged
Additionally, for patients with left ventricular failure, 18 and older as of July 2022 [40].
mechanical circulatory support and/or extracorporeal
membrane oxygenation should be considered as temporary IX. BENEFITS-RISKS ANALYSIS OF COVID-19
measures to aid in recovery. VACCINATION

Treatment recommendations for cardiac failure and A. Benefits

arrhythmias resulting from a response to COVID-19 The benefits of COVID-19 vaccination are assessed
immunization should follow guidelines-directed therapy. based on the prevention of hospitalizations, ICU admissions,
Initial therapy for heart failure involves medications such as fatalities, and COVID-19 cases. These endpoints are
beta-blockers, angiotensin-converting enzyme inhibitors, significant public health outcomes that are trackable and
sodium-glucose cotransporter 2 inhibitors, or angiotensin quantifiable. To estimate the number of avoidable COVID-
receptor-neprilysin inhibitors. Since most patients present 19 cases with a vaccine (CP) [41]. Factors such as vaccine
with chest pain, acute coronary syndromes should be ruled efficiency, duration of protection, vaccination coverage, and
out clinically and, if necessary, angiographically [37]. Most incidence rates are considered. The formula used
cases of myocarditis caused by mRNA vaccines have a incorporates hospitalization rates (IH) and vaccine
normal or nearly normal left ventricular ejection fraction, effectiveness against hospitalization (EH) to determine
and symptoms often resolve quickly. To relieve strain on the avoidable COVID-19 hospitalizations. Preventable ICU
left ventricle and provide temporary support in cases of left admissions and deaths are derived from hospitalization
ventricular failure, oxygenation (class IIA) should be fractions (HP), focusing on individual, age, sex, and
considered [38]. The poorly characterized immunological combined categories.
mechanisms of cardiac damage following COVID-19
vaccination make the relative risks and benefits of anti-  Duration of Vaccine Protection
inflammatory medications unclear; however, case studies According to Pfizer's ongoing trial, the vaccine
suggest activation of cellular immunity during the healing provides protection for six months. Sensitivity analyses
process. A strategy that balances the potential benefits and consider a 12-month protection duration.
risks of short-term corticosteroid use is suggested for
patients with severely affected left ventricular function.
Hajjo et al. (2020)[39] identified glucocorticoids as a

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Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology
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 Incidences of COVID-19 Cases 19 vaccination is recommended for all individuals aged 12

The study estimates hospitalization rates proceeding to years and older.
intensive care and the proportion of hospitalized patients
who die, using CDC COVID Data Tracker for incidence XI. CONCLUSION
rates from July 2021. Four-week averages are employed due
to fluctuating rates [42]. The development of myocarditis after receiving the
COVID-19 mRNA vaccine, while rare, highlights the need
 Risks for ongoing surveillance and monitoring of vaccine safety.
The risks associated with myocarditis and pericarditis Although myocarditis is more common in certain
following COVID-19 vaccination are significant and demographics, such as young males, the overall benefit-risk
compared with benefit endpoints such as hospitalizations assessment of COVID-19 vaccination remains strongly
and deaths. Excess cases are estimated by subtracting 2019 positive across all age and gender groups. Understanding the
rates from the study window [43]. pathophysiology, risk factors, and optimal management of
vaccine-related myocarditis is crucial for ensuring the safety
 Data and Assumptions and efficacy of vaccination programs. Collaborative
The study uses data from the FDA's BEST system, research and robust data collection will help refine
including the Optum health claims database, covering vaccination strategies and bolster public confidence in
hospital, physician, and prescription medication health COVID-19 immunization. Despite the rare instances of
insurance claims. The majority of myocarditis cases occur myocarditis, the broader benefits of vaccination in
during the 7-day risk window following vaccination, preventing severe COVID-19 illness, hospitalizations, and
highlighting the importance of rapid medical reporting [44]. mortality far outweigh the potential risks associated with
this adverse event. Continued vaccination efforts are
X. FUTURE DIRECTIONS AND RESEARCH essential in controlling the spread of COVID-19 and
NEEDS protecting global public health.

 Further research is needed to clarify the frequency and REFERENCES

risk factors of myocarditis following COVID-19
immunization, including genetic susceptibility, prognosis, [1]. H. Cheng et al., “Efficacy and Safety of COVID-19
mechanisms, gender differences, clinical outcomes, vaccines in Phase III trials: A Meta-Analysis,”
treatment approaches, and long-term effects. Vaccines, vol. 9, no. 6, p. 582, Jun. 2021, doi:
10.3390/vaccines9060582.
 Studies should investigate immune cell populations and
[2]. L. R. Baden et al., “Efficacy and safety of the mRNA-
their roles in COVID-19 development, immunity after
1273 SARS-COV-2 vaccine,” New England Journal of
vaccination, cardiomyopathy, and multisystem
Medicine, vol. 384, no. 5, pp. 403–416, Feb. 2021, doi:
inflammatory syndrome in children related to COVID-19
10.1056/nejmoa2035389.
and vaccinations.
[3]. J. Pillay et al., “Incidence, risk factors, natural history,
 Research should focus on myocardium histology, and hypothesised mechanisms of myocarditis and
immunohistochemistry, ultrastructural abnormalities, pericarditis following covid-19 vaccination: living
and their correlation with cardiac biomarkers and evidence syntheses and review,” BMJ, p. e069445, Jul.
imaging results in the context of COVID-19-related 2022, doi: 10.1136/bmj-2021-069445.
myocardial damage. [4]. Roth GA et al., “Correction,” Journal of the American
 Prospective screening for potential heart injury and College of Cardiology, vol. 77, no. 15, pp. 1958–1959,
myocarditis following COVID-19 vaccinations should Apr. 2021, doi: 10.1016/j.jacc.2021.02.039.
be conducted, with attention to age- and sex-related [5]. R. K. Wadhera, C. Shen, S. Gondi, S. Chen, D. S. Kazi,
disparities. and R. W. Yeh, “Cardiovascular deaths during the
 Investigate risk factors such as genetics, comorbidities, COVID-19 pandemic in the United States,” Journal of
immunity, or autoimmune profiles related to vaccine- the American College of Cardiology, vol. 77, no. 2, pp.
induced myocarditis or cardiac damage associated with 159–169, Jan. 2021, doi: 10.1016/j.jacc.2020.10.055.
COVID-19 [45]. [6]. E. Kontopantelis et al., “Excess deaths from COVID-
19 and other causes by region, neighbourhood
Establishing a collaborative registry for myocarditis deprivation level and place of death during the first 30
linked to COVID-19 immunization would be beneficial. weeks of the pandemic in England and Wales: A
This registry should include patient demographics, clinical retrospective registry study,” The Lancet Regional
presentation, biomarkers (e.g., cardiac troponin), diagnostic Health - Europe, vol. 7, p. 100144, Aug. 2021, doi:
results from cardiac MRI, echocardiography, and ECG, 10.1016/j.lanepe.2021.100144.
along with a bio-repository of blood and heart tissue [7]. D. Patriki, J. Kottwitz, J. Berg, U. Landmesser, T. F.
samples for rare post-vaccination health issues. Despite the Lüscher, and B. Heidecker, “Clinical Presentation and
low incidence of self-limited myocarditis, the benefit-risk Laboratory Findings in Men Versus Women with
assessment of COVID-19 vaccination shows a positive Myocarditis,” Journal of Women S Health, vol. 29, no.
balance for all age and sex groups. Consequently, COVID- 2, pp. 193–199, Feb. 2020, doi:
10.1089/jwh.2018.7618.

IJISRT24SEP1097 www.ijisrt.com 1640

Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24SEP1097

[8]. D. Mevorach et al., “Myocarditis after BNT162b2 [21]. S. Heymans, U. Eriksson, J. Lehtonen, and L. T.
mRNA Vaccine against Covid-19 in Israel,” New Cooper, “The quest for new approaches in myocarditis
England Journal of Medicine, vol. 385, no. 23, pp. and inflammatory cardiomyopathy,” Journal of the
2140–2149, Dec. 2021, doi: 10.1056/nejmoa2109730. American College of Cardiology, vol. 68, no. 21, pp.
[9]. N. P. Klein et al., “Surveillance for adverse events 2348–2364, Nov. 2016, doi:
after COVID-19 mRNA vaccination,” JAMA, vol. 326, 10.1016/j.jacc.2016.09.937.
no. 14, p. 1390, Oct. 2021, doi: [22]. M. Müller, L. T. Cooper, and B. Heidecker, “Diagnosis,
10.1001/jama.2021.15072. risk stratification and management of myocarditis,”
[10]. J. Montgomery et al., “Myocarditis following Heart, vol. 108, no. 18, pp. 1486–1497, Dec. 2021, doi:
immunization with mRNA COVID-19 vaccines in 10.1136/heartjnl-2021-319027.
members of the US military,” JAMA Cardiology, vol. 6, [23]. W. Woo et al., “Clinical characteristics and prognostic
no. 10, p. 1202, Oct. 2021, doi: factors of myocarditis associated with the mRNA
10.1001/jamacardio.2021.2833. COVID‐19 vaccine,” Journal of Medical Virology, vol.
[11]. S. Greulich et al., “Predictors of Mortality in Patients 94, no. 4, pp. 1566–1580, Dec. 2021, doi:
with Biopsy‐Proven Viral Myocarditis: 10‐Year 10.1002/jmv.27501.
Outcome data,” Journal of the American Heart [24]. M. E. Oster et al., “Myocarditis cases reported after
Association, vol. 9, no. 16, Aug. 2020, doi: mRNA-Based COVID-19 vaccination in the US from
10.1161/jaha.119.015351. December 2020 to August 2021,” JAMA, vol. 327, no.
[12]. P. E. Tam, “Coxsackievirus Myocarditis: Interplay 4, p. 331, Jan. 2022, doi: 10.1001/jama.2021.24110.
between Virus and Host in the Pathogenesis of Heart [25]. M. Gnecchi et al., “Myocarditis in a 16-year-old boy
Disease,” Viral Immunology, vol. 19, no. 2, pp. 133– positive for SARS-CoV-2,” The Lancet, vol. 395, no.
146, Jun. 2006, doi: 10.1089/vim.2006.19.133. 10242, p. e116, Jun. 2020, doi: 10.1016/s0140-
[13]. C. B. Coyne and J. M. Bergelson, “Virus-Induced Abl 6736(20)31307-6.
and Fyn Kinase Signals Permit Coxsackievirus Entry [26]. A. K. Verma, K. J. Lavine, and C.-Y. Lin,
through Epithelial Tight Junctions,” Cell, vol. 124, no. “Myocarditis after Covid-19 mRNA Vaccination,”
1, pp. 119–131, Jan. 2006, doi: New England Journal of Medicine, vol. 385, no. 14, pp.
10.1016/j.cell.2005.10.035. 1332–1334, Sep. 2021, doi: 10.1056/nejmc2109975.
[14]. P. Schmerler et al., “Mortality and morbidity in [27]. L. T. Cooper, “Myocarditis,” New England Journal of
different immunization protocols for experimental Medicine, vol. 360, no. 15, pp. 1526–1538, Apr. 2009,
autoimmune myocarditis in rats,” Acta Physiologica, doi: 10.1056/nejmra0800028.
vol. 210, no. 4, pp. 889–898, Feb. 2014, doi: [28]. E. Saricam, Y. Saglam, and T. Hazirolan, “Clinical
10.1111/apha.12227. evaluation of myocardial involvement in acute
[15]. X. Clemente-Casares et al., “A CD103+ Conventional myopericarditis in young adults,” BMC
Dendritic Cell Surveillance System Prevents Cardiovascular Disorders, vol. 17, no. 1, May 2017,
Development of Overt Heart Failure during Subclinical doi: 10.1186/s12872-017-0564-8.
Viral Myocarditis,” Immunity, vol. 47, no. 5, pp. 974- [29]. H. R. Figulla, “Transformation of myocarditis and
989.e8, Nov. 2017, doi: 10.1016/j.immuni.2017.10.011. inflammatory cardiomyopathy to idiopathic dilated
[16]. D. Zehn and M. J. Bevan, “T Cells with Low Avidity cardiomyopathy: facts and fiction,” Medical
for a Tissue-Restricted Antigen Routinely Evade Microbiology and Immunology, vol. 193, no. 2–3, pp.
Central and Peripheral Tolerance and Cause 61–64, May 2004, doi: 10.1007/s00430-003-0205-y.
Autoimmunity,” Immunity, vol. 25, no. 2, pp. 261–270, [30]. C. Costa and F. Moniati, “The Epidemiology of
Aug. 2006, doi: 10.1016/j.immuni.2006.06.009. COVID-19 Vaccine-Induced Myocarditis,” Advances
[17]. Y. Li et al., “Enteroviral capsid protein VP1 is present in Medicine, vol. 2024, pp. 1–17, Apr. 2024, doi:
in myocardial tissues from some patients with 10.1155/2024/4470326.
myocarditis or dilated cardiomyopathy,” Circulation, [31]. R. J. Benschop et al., “The effect of anti-SARS-CoV-2
vol. 101, no. 3, pp. 231–234, Jan. 2000, doi: monoclonal antibody, bamlanivimab, on endogenous
10.1161/01.cir.101.3.231. immune response to COVID-19 vaccination,” medRxiv
[18]. F. Caso et al., “Could Sars-coronavirus-2 trigger (Cold Spring Harbor Laboratory), Dec. 2021, doi:
autoimmune and/or autoinflammatory mechanisms in 10.1101/2021.12.15.21267605.
genetically predisposed subjects?,” Autoimmunity [32]. T. K. Boehmer et al., “Association between COVID-
Reviews, vol. 19, no. 5, p. 102524, May 2020, doi: 19 and myocarditis using Hospital-Based
10.1016/j.autrev.2020.102524. Administrative Data — United States, March 2020–
[19]. M. Fraser et al., “COVID-19-Associated myocarditis: January 2021,” MMWR Morbidity and Mortality
an evolving concern in cardiology and beyond,” Weekly Report, vol. 70, no. 35, pp. 1228–1232, Sep.
Biology, vol. 11, no. 4, p. 520, Mar. 2022, doi: 2021, doi: 10.15585/mmwr.mm7035e5.
10.3390/biology11040520. [33]. D. Bojkova et al., “SARS-CoV-2 infects and induces
[20]. H. R. Figulla, “Transformation of myocarditis and cytotoxic effects in human cardiomyocytes,”
inflammatory cardiomyopathy to idiopathic dilated Cardiovascular Research, vol. 116, no. 14, pp. 2207–
cardiomyopathy: facts and fiction,” Medical 2215, Sep. 2020, doi: 10.1093/cvr/cvaa267.
Microbiology and Immunology, vol. 193, no. 2–3, pp.
61–64, May 2004, doi: 10.1007/s00430-003-0205-y.

IJISRT24SEP1097 www.ijisrt.com 1641

Volume 9, Issue 9, September – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24SEP1097

[34]. T. A. McDonagh et al., “Corrigendum to: 2021 ESC [45]. B. Bozkurt, I. Kamat, and P. J. Hotez, “Myocarditis
Guidelines for the diagnosis and treatment of acute and with COVID-19 mRNA vaccines,” Circulation, vol.
chronic heart failure: Developed by the Task Force for 144, no. 6, pp. 471–484, Aug. 2021, doi:
the diagnosis and treatment of acute and chronic heart 10.1161/circulationaha.121.056135.
failure of the European Society of Cardiology (ESC)
With the special contribution of the Heart Failure
Association (HFA) of the ESC,” European Heart
Journal, vol. 42, no. 48, p. 4901, Oct. 2021, doi:
10.1093/eurheartj/ehab670.
[35]. “Corrigendum to: ‘A comprehensive characterization
of acute heart failure with preserved versus mildly
reduced versus reduced ejection fraction – insights
from the ESC‐HFA EORP Heart Failure Long‐Term
Registry’ and articles listed below,” European Journal
of Heart Failure, vol. 25, no. 3, p. 443, Feb. 2023, doi:
10.1002/ejhf.2789.
[36]. R. D. Kociol et al., “Recognition and initial
management of fulminant myocarditis,” Circulation,
vol. 141, no. 6, Feb. 2020, doi:
10.1161/cir.0000000000000745.
[37]. F. Ceban et al., “COVID-19 vaccination for the
prevention and treatment of long COVID: A
systematic review and meta-analysis,” Brain Behavior
and Immunity, vol. 111, pp. 211–229, Jul. 2023, doi:
10.1016/j.bbi.2023.03.022.
[38]. B. Raman, D. A. Bluemke, T. F. Lüscher, and S.
Neubauer, “Long COVID: post-acute sequelae of
COVID-19 with a cardiovascular focus,” European
Heart Journal, vol. 43, no. 11, pp. 1157–1172, Feb.
2022, doi: 10.1093/eurheartj/ehac031.
[39]. R. R. Ling et al., “Myopericarditis following COVID-
19 vaccination and non-COVID-19 vaccination: a
systematic review and meta-analysis,” The Lancet
Respiratory Medicine, vol. 10, no. 7, pp. 679–688, Jul.
2022, doi: 10.1016/s2213-2600(22)00059-5.
[40]. M. Marshall et al., “Symptomatic acute myocarditis in
7 adolescents after Pfizer-BioNTech COVID-19
vaccination,” PEDIATRICS, vol. 148, no. 3, Sep. 2021,
doi: 10.1542/peds.2021-052478.
[41]. D. K. Shay, T. T. Shimabukuro, and F. DeStefano,
“Myocarditis occurring after immunization with
mRNA-Based COVID-19 vaccines,” JAMA
Cardiology, vol. 6, no. 10, p. 1115, Oct. 2021, doi:
10.1001/jamacardio.2021.2821.
[42]. K.-H. Son, S.-H. Kwon, H.-J. Na, Y. Baek, I. Kim, and
E.-K. Lee, “Quantitative Benefit–Risk Assessment of
COVID-19 vaccines using the Multi-Criteria Decision
Analysis,” Vaccines, vol. 10, no. 12, p. 2029, Nov.
2022, doi: 10.3390/vaccines10122029.
[43]. M. Wallace et al., “A summary of the Advisory
Committee for Immunization Practices (ACIP) use of a
benefit-risk assessment framework during the first year
of COVID-19 vaccine administration in the United
States,” Vaccine, vol. 41, no. 44, pp. 6456–6467, Oct.
2023, doi: 10.1016/j.vaccine.2023.07.037.
[44]. J. R. Su et al., “Myopericarditis after vaccination,
Vaccine Adverse Event Reporting System (VAERS),
1990–2018,” Vaccine, vol. 39, no. 5, pp. 839–845, Jan.
2021, doi: 10.1016/j.vaccine.2020.12.046.

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