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Science China. Life Sciences Sep 2023Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and... (Review)
Review
Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis, whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.
Topics: Humans; Myocarditis; COVID-19; Inflammation; Myocytes, Cardiac; Immunomodulation
PubMed: 37002488
DOI: 10.1007/s11427-022-2273-3 -
International Journal of Cardiology Mar 2024Gene therapy is a technique to correct genetic abnormalities, through introduction of a functional gene or through direct genome editing. Adeno-associated virus... (Review)
Review
Gene therapy is a technique to correct genetic abnormalities, through introduction of a functional gene or through direct genome editing. Adeno-associated virus (AAV)-mediated gene replacement shows promise for targeted therapies in treatment of inherited cardiomyopathies and is the most used approach in clinical trials. However, immune responses from the host to the virus and gene product pose delivery and safety challenges. This review explores the immunological reactions to AAV-based gene therapy, their potential toxic effects, with a focus on myocarditis, and future directions for gene therapy.
Topics: Humans; Myocarditis; Genetic Therapy; Genetic Vectors; Dependovirus
PubMed: 38030043
DOI: 10.1016/j.ijcard.2023.131617 -
Cureus Oct 2023There has been a rise in cardiovascular events following the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a strain that caused... (Review)
Review
There has been a rise in cardiovascular events following the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a strain that caused coronavirus disease 2019 (COVID-19). Although rare, there has been an increase in reports of myocarditis secondary to both individuals infected by the strain and those who received the COVID-19 mRNA vaccine. The focus of this study is to determine the risk of myocarditis associated with the COVID-19 vaccine and SARS-CoV-2 infection. Relevant literature was collected using the search engines PubMed, Google Scholar, and the WHO Global Literature on Coronavirus Disease. Randomized controlled clinical trials and cohort studies reporting the risk of myocarditis induced by SARS-CoV-2 infection and COVID-19 vaccines were used. A meta-analysis was conducted using the inverse variance method using RevMan application software. A meta-analysis of the compiled data showed a mean risk ratio of 4.74 (95% confidence interval (CI) = 2.40 to 9.36; p < 0.0000100), which indicates there is a significant difference in the risk of COVID-19-induced myocarditis in those with unspecified vaccination status compared to the non-infected population. A meta-analysis of the selected data found a mean risk ratio of 5.01 (95% CI = 4.14 to 6.08; p < 0.0000100), indicating a significant difference in the risk of COVID-19-induced myocarditis between those who are unvaccinated and the non-infected population. Upon a meta-analysis of the selected data set, a mean risk ratio of 2.55 (95% CI = 0.840 to 7.74; p = 0.100) was found, indicating no significant difference in the risk of vaccine-induced myocarditis between those with a vaccinated vaccination status and that of the non-infected population. The result of this meta-analysis showed that infection with SARS-CoV-2 in unvaccinated patients carries a statistically significant increased risk of acquiring myocarditis while those receiving the vaccination do not share this same risk.
PubMed: 38046477
DOI: 10.7759/cureus.48059 -
Global Cardiology Science & Practice Sep 2023The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic... (Review)
Review
The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic phases, the infection had been initially considered a primary pulmonary disease. However, increasing evidence has demonstrated a wide range of possible cardiac involvement. Most of systemic and cardiac damage is likely sustained by a complex interplay between inflammatory, immune-related and thrombotic mechanisms. Biventricular failure and myocardial damage with elevation of cardiac biomarkers have been reported in COVID-19 patients, although histological demonstration of acute myocarditis has been rarely documented. Indeed while cardiac magnetic resonance findings include different patterns of myocardial involvement in terms of late gadolinium enhancement, histological data from necropsy and endomyocardial biopsy showed peculiar inflammatory patterns, mostly composed by macrophages. On the other hand COVID-19 vaccines based on mRN technology have been also associated with increased risk of myocarditis. COVID-19 and mRNA vaccine-related myocarditis present different clinical and imaging presentations and recent data suggest the presence of distinctive immunological mechanisms involved.
PubMed: 38404624
DOI: 10.21542/gcsp.2023.28 -
European Journal of Pediatrics Nov 2023Coronavirus disease 2019 in children presents with distinct phenotype in comparison to adults. Overall, the pediatric infection with a generally milder clinical course... (Review)
Review
Coronavirus disease 2019 in children presents with distinct phenotype in comparison to adults. Overall, the pediatric infection with a generally milder clinical course of the acute infection compared to adults still faces several unknown aspects. Specifically, the presence of a wide range of inflammatory manifestations, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and long COVID in the period after infection suggests a particular susceptibility of some children upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Albeit peculiar complications such as long covid are less frequent in children compared to adults, research on the relationship between inflammatory syndromes and SARS-CoV-2 is rapidly evolving. Conclusions: new studies and findings continue to emerge, providing further insights into the underlying mechanisms and potential therapeutic strategies. In the present work, we revised current knowledge of the main factors accounting for such variability upon SARS-CoV-2 infection over the pediatric age group. What is Known: • COVID19 in children overall showed a milder course compared to adults during the acute phase of the infection. • Children showed to be susceptible to a wide range of post infectious complications including multisystem inflammatory syndrome in children (MIS-C), myocarditis, neuroinflammation, and long COVID. What is New: • Mechanisms underlying susceptibility to a severe course of the infection were recently shown to pertain to the host. • A specific combination of HLA was recently shown to be associated to higher susceptibility to MIS-C in children.
Topics: Adult; Child; Humans; COVID-19; Post-Acute COVID-19 Syndrome; RNA, Viral; SARS-CoV-2; Myocarditis
PubMed: 37702769
DOI: 10.1007/s00431-023-05184-w -
Hellenic Journal of Cardiology : HJC =... 2023Paediatric cardiomyopathies form a heterogeneous group of disorders characterized by structural and electrical abnormalities of the heart muscle, commonly due to a gene... (Review)
Review
Paediatric cardiomyopathies form a heterogeneous group of disorders characterized by structural and electrical abnormalities of the heart muscle, commonly due to a gene variant of the myocardial cell structure. Mostly inherited as a dominant or occasionally recessive trait, they might be part of a syndromic disorder of underlying metabolic or neuromuscular defects or combine early developing extracardiac abnormalities (i.e., Naxos disease). The annual incidence of 1 per 100,000 children appears higher during the first two years of life. Dilated and hypertrophic cardiomyopathy phenotypes share an incidence of 60% and 25%, respectively. Arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy, and left ventricular noncompaction are less commonly diagnosed. Adverse events such as severe heart failure, heart transplantation, or death usually appear early after the initial presentation. In ARVC patients, high-intensity aerobic exercise has been associated with worse clinical outcomes and increased penetrance in at-risk genotype-positive relatives. Acute myocarditis in children has an incidence of 1.4-2.1 cases/per 100,000 children per year, with a 6-14% mortality rate during the acute phase. A genetic defect is considered responsible for the progression to dilated cardiomyopathy phenotype. Similarly, a dilated or arrhythmogenic cardiomyopathy phenotype might emerge with an episode of acute myocarditis in childhood or adolescence. This review provides an overview of childhood cardiomyopathies focusing on clinical presentation, outcome, and pathology.
Topics: Adolescent; Humans; Child; Myocarditis; Cardiomyopathies; Myocardium; Arrhythmogenic Right Ventricular Dysplasia; Phenotype
PubMed: 36870438
DOI: 10.1016/j.hjc.2023.02.007 -
Frontiers in Pharmacology 2023Autoimmune hepatitis (AIH) is the inflammation of the liver with clear-cut interface hepatitis and piecemeal necrosis located at the boundary between portal areas and...
Autoimmune hepatitis (AIH) is the inflammation of the liver with clear-cut interface hepatitis and piecemeal necrosis located at the boundary between portal areas and periportal hepatocytes, and characterized by autoimmunity to hepatocytes with an increase in the antinuclear antibody. After the disastrous SARS-CoV-2 pandemic flagellated several countries, several vaccines have been commercialized and have become a ground for social responsibility. The mRNA vaccines, issued by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273), do not use prebuilt viruses to supply the antigen in the subject's body and are not perfect but have been useful in tackling the pandemic. Nevertheless, both myocarditis and AIH have been reported as side effects of the vaccination programs in addition to thromboembolic events. Here, we explore this topic and give a data-based perspective, gathering a comparison between the titin protein of the sarcomere and myocarditis. The isolation of a gene using the serum from a patient with autoimmune scleroderma recognized an epitope on chromosomes (condensed mitotic form) in both human cultured cells and early embryos. It revealed that this gene encodes a homolog of the vertebrate titin (D-Titin). Moreover, anti-titin antibodies have been found in a subset of patients with , a neuromuscular junction disease that is mostly associated with autoimmune antibodies, such as the anti-acetylcholine receptor antibody. The co-existence of and autoimmune hepatitis is rare, and a cohort of patients with anti-titin antibodies seems to be highly relevant. In consideration of these data and the number of patients who may not be symptomatic, we postulated that autoimmune phenomena may not be exceedingly rare, following the administration of mRNA technology-based vaccines, and a balance between pros and cons in administrating boosters is critical.
PubMed: 37601060
DOI: 10.3389/fphar.2023.1190367 -
Frontiers in Immunology 2024For many decades viral infections have been suspected as 'triggers' of autoimmune disease, but mechanisms for how this could occur have been difficult to establish.... (Review)
Review
For many decades viral infections have been suspected as 'triggers' of autoimmune disease, but mechanisms for how this could occur have been difficult to establish. Recent studies have shown that viral infections that are commonly associated with viral myocarditis and other autoimmune diseases such as coxsackievirus B3 (CVB3) and SARS-CoV-2 target mitochondria and are released from cells in mitochondrial vesicles that are able to activate the innate immune response. Studies have shown that Toll-like receptor (TLR)4 and the inflammasome pathway are activated by mitochondrial components. Autoreactivity against cardiac myosin and heart-specific immune responses that occur after infection with viruses where the heart is not the primary site of infection (e.g., CVB3, SARS-CoV-2) may occur because the heart has the highest density of mitochondria in the body. Evidence exists for autoantibodies against mitochondrial antigens in patients with myocarditis and dilated cardiomyopathy. Defects in tolerance mechanisms like autoimmune regulator gene (AIRE) may further increase the likelihood of autoreactivity against mitochondrial antigens leading to autoimmune disease. The focus of this review is to summarize current literature regarding the role of viral infection in the production of extracellular vesicles containing mitochondria and virus and the development of myocarditis.
Topics: Humans; Myocarditis; Autoimmunity; Coxsackievirus Infections; Enterovirus B, Human; Autoimmune Diseases; Mitochondria; Extracellular Vesicles
PubMed: 38550582
DOI: 10.3389/fimmu.2024.1374796 -
Frontiers in Cardiovascular Medicine 2023
PubMed: 38034393
DOI: 10.3389/fcvm.2023.1321494 -
Biomedicines Apr 2024In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac... (Review)
Review
In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart.
PubMed: 38672187
DOI: 10.3390/biomedicines12040832