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1.
J Korean Med Sci ; 36(32): e229, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34402228

RESUMO

Increasing rates of coronavirus disease 2019 (COVID-19) vaccination coverage will result in more vaccine-related side effects, including acute myocarditis. In Korea, we present a 24-year-old male with acute myocarditis following COVID-19 vaccination (BNT162b2). His chest pain developed the day after vaccination and cardiac biomarkers were elevated. Echocardiography showed minimal pericardial effusion but normal myocardial contractility. Electrocardiography revealed diffuse ST elevation in lead II, and V2-5. Cardiac magnetic resonance images showed the high signal intensity of T2- short tau inversion recovery image, the high value of T2 mapping sequence, and late gadolinium enhancement in basal inferior and inferolateral wall. It was presumed that COVID-19 mRNA vaccination was probably responsible for acute myocarditis. Clinical course of the patient was favorable and he was discharged without any adverse event.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Coração/diagnóstico por imagem , Miocardite/diagnóstico por imagem , Miocardite/patologia , Miocárdio/patologia , COVID-19/imunologia , COVID-19/prevenção & controle , Dor no Peito/patologia , Ecocardiografia , Eletrocardiografia , Humanos , Imageamento por Ressonância Magnética , Masculino , República da Coreia , Vacinação/efeitos adversos , Adulto Jovem
2.
J Korean Med Sci ; 36(32): e232, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34402230

RESUMO

BACKGROUND: Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021. However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population. METHODS: A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019. RESULTS: Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6-12.9 years; range, 11 days-17.8 years), and male was 61%. In adolescents aged 12-17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1-5 years), 0.67 (6-11 years) and 1.22 (12-17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014). CONCLUSION: The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Miocardite/epidemiologia , Miocardite/patologia , Pericardite/epidemiologia , Pericardite/patologia , Adolescente , COVID-19/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Vacinação/efeitos adversos
3.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445539

RESUMO

BACKGROUND: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. METHODS: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. RESULTS: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. CONCLUSIONS: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.


Assuntos
Infecções por Coxsackievirus/complicações , Enterovirus Humano B/patogenicidade , Abrigo para Animais/estatística & dados numéricos , Miocardite/patologia , Plásticos/efeitos adversos , Animais , Infecções por Coxsackievirus/virologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/etiologia , Miocardite/virologia , Fatores Sexuais
5.
Aging (Albany NY) ; 13(13): 17473-17488, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214050

RESUMO

BACKGROUND: Inflammation process is an important determinant for subsequent changes in cardiac function and remodeling after acute myocardial infarction (MI). Recent studies have implicated that ALK4 haplodeficiency improves cardiac function after MI. However, it remains unknown if the beneficial effects are partly attributed to ALK4 haplodeficiency-induced modulation on inflammatory response in the inflammatory phase of MI. In this research, we aimed to explore the mechanism of ALK4 haplodeficiency in the inflammatory stage of MI. METHODS: ALK4, CD16, and CD14 were detected in peripheral blood mononuclear cells (PBMCs) isolated from MI patients and healthy volunteers. ALK4 haplodeficiency (ALK4+/-) mice and wild-type (WT) littermates were randomly divided into the sham group and the MI group. Inflammation cytokines and chemokines were measured. Echocardiography and intracardiac electrophysiological recordings were performed on the 3rd day and the 7th day after MI operation. ALK4 expression and inflammation cytokines were also detected in LPS- or IL-4-stimulated bone marrow-derived macrophages (BMDM) from the ALK4+/- mice and WT littermates. RESULTS: ALK4 gene expression in circulating monocytes of MI patients was higher than that in those of healthy volunteers. Cardiac inflammation and vulnerability of ventricular arrhythmia after acute myocardial injury are significantly alleviated in ALK4+/- mice as compared to WT littermates. On the 3rd day post-MI, the level of M1 macrophages were decreased in ALK4+/- mice as compared to WT littermates, while the level of M2 macrophages were increased on the 7th day post-MI. BMDM isolated from ALK4+/- mice displayed reduced secretion of pro-inflammation cytokines after stimulation by LPS in hypoxic condition and increased secretion of anti-inflammation cytokines after stimulation by IL-4. As a result, the haplodeficiency of ALK4 might be responsible for reduced inflammation response in the post-MI stage. CONCLUSIONS: ALK4 haplodeficiency reduces cardiac inflammation, improves cardiac function, and finally reduces the vulnerability of ventricular arrhythmia in the inflammatory stage after MI.


Assuntos
Receptores de Ativinas Tipo I/genética , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/genética , Infarto do Miocárdio/complicações , Infarto do Miocárdio/genética , Miocardite/patologia , Animais , Estimulação Cardíaca Artificial , Citocinas/metabolismo , Ecocardiografia , Proteínas Ligadas por GPI/genética , Voluntários Saudáveis , Humanos , Receptores de Lipopolissacarídeos/genética , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de IgG/genética
6.
JAMA Neurol ; 78(8): 948-960, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115106

RESUMO

Importance: Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19. Objective: To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. Design, Setting, and Participants: This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19. Main Outcomes and Measures: Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates. Results: Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy. Conclusions and Relevance: In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.


Assuntos
COVID-19/patologia , Músculo Esquelético/patologia , Miocardite/patologia , Miocárdio/patologia , Miosite/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Linfócitos T CD8-Positivos/patologia , COVID-19/metabolismo , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Estudos de Casos e Controles , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Células Matadoras Naturais/patologia , Leucócitos/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Miosite/metabolismo , RNA Viral/metabolismo , SARS-CoV-2 , Sarcolema/metabolismo , Fatores de Tempo
7.
J Zoo Wildl Med ; 52(2): 853-857, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130436

RESUMO

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.


Assuntos
Doenças dos Símios Antropoides/patologia , Eosinofilia/veterinária , Miocardite/veterinária , Miocárdio/patologia , Pan troglodytes , Animais , Eosinofilia/patologia , Evolução Fatal , Masculino , Miocardite/patologia , Necrose/patologia , Necrose/veterinária
8.
Cardiovasc Pathol ; 54: 107361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34174415

RESUMO

COVID-19 has a significant effect upon the cardiovascular system. While a number of different cardiovascular histopathologies have been described at post-mortem examination, the incidence of typical viral myocarditis in COVID-19 positive patients appears very low [1-3]. In this study, we further characterize and quantify the inflammatory cell infiltrate in a COVID-19 study cohort and compare the findings to both an age and disease matched control cohort and a cohort of patients diagnosed with typical inflammatory myocarditis. All study and control cohorts had 1 or more of the comorbidities most commonly associated with severe disease (hypertension, type II diabetes, obesity, or known cardiovascular disease). The results demonstrate a skewed distribution of the number of CD68+ cells in COVID-19 hearts, with upper quantiles showing a significant increase as compared to both matched control hearts, and those with myocarditis. In contrast, hearts from typical inflammatory myocarditis contained increased numbers of CD4+, and CD8+ cells compared to both COVID-19 and control cohorts. In conclusion, the presence of an increased number of CD68+ cells suggests that COVID-19 may incite a form of myocarditis different from typical viral myocarditis, and associated with diffusely infiltrative cells of monocytes/macrophage lineage.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , COVID-19/imunologia , Macrófagos/imunologia , Miocardite/imunologia , Miocárdio/imunologia , Adulto , Idoso , Autopsia , Biomarcadores/análise , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imuno-Histoquímica , Macrófagos/virologia , Masculino , Pessoa de Meia-Idade , Miocardite/mortalidade , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade
9.
J Intern Med ; 290(3): 655-665, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33872433

RESUMO

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.


Assuntos
COVID-19/mortalidade , COVID-19/patologia , Causas de Morte , Alvéolos Pulmonares/patologia , Embolia Pulmonar/patologia , Tromboembolia/patologia , Idoso , Autopsia , Capilares/patologia , Feminino , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Pandemias , Reação em Cadeia da Polimerase , Artéria Pulmonar/patologia , SARS-CoV-2 , Microangiopatias Trombóticas/patologia
10.
PLoS Negl Trop Dis ; 15(4): e0008964, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33826636

RESUMO

Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken during both acute and chronic T. cruzi infection utilizing the FAT-ATTAC murine model (that allows modulation of fat mass) to understand the consequences of the loss of adipocytes in the regulation of cardiac parasite load, parasite persistence, inflammation, mitochondrial stress, ER stress, survival, CCC progression and CCC severity. Mice were infected intraperitoneally with 5x104 and 103 trypomastigotes to generate acute and chronic Chagas models, respectively. Ablation of adipocytes was carried out in uninfected and infected mice by treatment with AP21087 for 10 days starting at 15DPI (acute infection) and at 65DPI (indeterminate infection). During acute infection, cardiac ultrasound imaging, histological, and biochemical analyses demonstrated that fat ablation increased cardiac parasite load, cardiac pathology and right ventricular dilation and decreased survival. During chronic indeterminate infection ablation of fat cells increased cardiac pathology and caused bi-ventricular dilation. These data demonstrate that dysfunctional adipose tissue not only affects cardiac metabolism but also the inflammatory status, morphology and physiology of the myocardium and increases the risk of progression and severity of CCC in murine Chagas disease.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Miocardite/metabolismo , Adipogenia , Tecido Adiposo Branco/metabolismo , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , LDL-Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Miocardite/parasitologia , Miocardite/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Carga Parasitária , Ultrassonografia Doppler
11.
Int J Biochem Cell Biol ; 134: 105973, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831592

RESUMO

Acute myocarditis is an inflammatory condition of the heart characterised by cellular injury and the influx of leucocytes, including neutrophils, monocytes, macrophages and lymphocytes. While this response is vital for tissue repair, excessive scar deposition and maladaptive ventricular remodelling can result in a legacy of heart failure. It is increasingly recognised as a clinical phenomenon due, in part, to increased availability of cardiac magnetic resonance imaging in patients presenting with chest pain in the absence of significant coronary artery disease. Emerging epidemiological evidence has associated myocarditis with poor outcomes in the context of left ventricular impairment, and even when the left ventricle is preserved outcomes are less benign than once thought. Despite this, our understanding of the contribution of the inflammatory response to the pathophysiology of acute myocarditis lags behind that of acute myocardial infarction, which is the vanguard cardiovascular condition for inflammation research. We recently reviewed monocyte and macrophage phenotype and function in acute myocardial infarction, concluding that their plasticity and heterogeneity might account for conflicting evidence from attempts to target specific leucocyte subpopulations. Here, we revise our understanding of myocardial inflammation, which is predominantly derived from myocardial infarction research, review experimental evidence for the immune response in acute myocarditis, focusing on innate immunity, and discuss potential future directions for immunotherapy research in acute myocarditis.


Assuntos
Inflamação/imunologia , Miocardite/imunologia , Animais , Humanos , Imunidade Inata , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/patologia , Monócitos/imunologia , Monócitos/patologia , Miocardite/patologia , Neutrófilos/imunologia , Neutrófilos/patologia , Remodelação Ventricular
13.
Med Sci Monit ; 27: e929512, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33866323

RESUMO

BACKGROUND Sepsis is a serious clinical problem that results from the systemic response of the body to infection. Left ventricular (LV) diastolic dysfunction is increasingly appreciated as a contributor to morbidity and mortality in sepsis. Animal models may offer a method of studying diastolic dysfunction while controlling for many potential clinical confounders, such as sepsis duration, premorbid condition, and therapeutic interventions. This study sought to evaluate an endotoxemia (LPS) rodent model of sepsis, with regard to echocardiographic evidence, including tissue Doppler, of LV diastolic dysfunction and histopathology findings. MATERIAL AND METHODS Fourteen male Sprague-Dawley rats were randomly allocated (1: 1) to LPS or saline (control). Mean arterial blood pressure (MAP) was measured through cannulation of the carotid artery. After a 30-min stabilization, baseline assessment with echocardiography and blood collection was performed. Rats were administered 0.9% saline or LPS (10 mg/mL). Follow-up echocardiography and blood collection were performed after 2 h. Hearts were removed post-mortem and pathology studied using histology and immunohistochemistry. RESULTS LPS was associated with hypotension (MAP 81.86±31.67 mmHg; 124.29±20.16; p=0.02) and LV impaired relaxation (myocardial early diastolic velocity [e'] 0.06±0.02 m/s; 0.09±0.02; P=0.008). Histopathology and immunohistochemistry demonstrated evidence of interstitial myocarditis (hydropic changes and inflammation). CONCLUSIONS LPS was associated with both diastolic dysfunction (impaired relaxation) and interstitial myocarditis. These features may offer a link between the structural and functional changes that have previously been described separately in clinical sepsis. This may facilitate further studies focused upon the mechanism and potential benefit treatment of sepsis-associated cardiac dysfunction.


Assuntos
Ventrículos do Coração/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Sepse/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Animais , Diástole , Modelos Animais de Doenças , Ecocardiografia Doppler , Ventrículos do Coração/patologia , Humanos , Imuno-Histoquímica , Masculino , Miocardite/patologia , Ratos , Ratos Sprague-Dawley , Sepse/patologia , Disfunção Ventricular Esquerda/patologia
14.
J Pathol Clin Res ; 7(4): 326-337, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33837673

RESUMO

While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from 23 autopsies of COVID-19 patients, comparing the findings with control tissue. Myocardium from autopsies of COVID-19 patients was categorised into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive (n = 14) or negative (n = 9) based on the presence of viral RNA as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Control tissue was selected from autopsies without COVID-19 (n = 10) with similar clinical sequelae. Histological characteristics were scored by ordinal and/or categorical grading. Five RT-PCR-positive cases underwent in situ hybridisation (ISH) for SARS-CoV-2. Patients with lethal COVID-19 infection were mostly male (78%) and had a high incidence of hypertension (91%), coronary artery disease (61%), and diabetes mellitus (48%). Patients with positive myocardial RT-PCR died earlier after hospital admission (5 versus 12 days, p < 0.001) than patients with negative RT-PCR. An increased severity of fibrin deposition, capillary dilatation, and microhaemorrhage was observed in RT-PCR-positive myocardium than in negatives and controls, with a positive correlation amongst these factors All cases with increased cardioinflammatory infiltrate, without myocyte necrosis (n = 4) or with myocarditis (n = 1), were RT-PCR negative. ISH revealed positivity of viral RNA in interstitial cells. Myocardial capillary dilatation, fibrin deposition, and microhaemorrhage may be the histomorphological correlate of COVID-19-associated coagulopathy. Increased cardioinflammation including one case of myocarditis was only detected in RT-PCR-negative hearts with significantly longer hospitalisation time. This may imply a secondary immunological response warranting further characterisation.


Assuntos
COVID-19/patologia , COVID-19/virologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , SARS-CoV-2/patogenicidade , Adulto , Autopsia/métodos , COVID-19/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/etiologia , Miocardite/patologia , Miocárdio/patologia , RNA Viral/genética
15.
Pediatr Infect Dis J ; 40(5): e173-e178, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33847291

RESUMO

BACKGROUND: Acute myocarditis (AM) is defined as inflammation of the myocardium. The aim of our study is a comparative analysis of the differences between AM related and unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The retrospective study included children with AM treated from January 2018 to November 2020. RESULTS: The study included 24 patients; 7 of 24 had AM related to SARS-CoV-2 and they were older than 7. They were more likely to have abdominal pain (P = 0.014), headache (P = 0.003), cutaneous rash (P = 0.003), and conjunctivitis (P = 0.003), while fulminant myocarditis was commonly registered in AM unrelated to SARS-CoV-2 (P = 0.04). A multisystem inflammatory syndrome in children associated with COVID-19 was diagnosed in six adolescents. Patients with AM related SARS-CoV-2 had lower serum cardiac troponin I (cTnI) (P = 0.012), and platelets (P < 0.001), but had a higher C-reactive protein (CRP) value (P = 0.04), and N-terminal-pro hormone BNP in comparison to patients with AM unrelated to SARS-CoV-2. The patients with AM related to SARS-CoV-2 had significant reduction of CRP (P = 0.007). Inotropic drug support was used for shorter durations in patients with AM related to SARS-CoV-2, than in others (P = 0.02). Children with AM related to SARS-CoV-2 had significant improvement of left ventricle systolic function on the third day in hospital (P = 0.001). Patients with AM unrelated to SARS-CoV-2 AM had more frequent adverse outcomes (P = 0.04; three died and four dilated cardiomyopathy). CONCLUSIONS: In contrast to patients with AM unrelated to SARS-CoV-2, patients with AM related to SARS-CoV-2 had a higher CRP value, polymorphic clinical presentation, shorter durations of inotropic drugs use as well as prompt recovery of left ventricle systolic function.


Assuntos
COVID-19/patologia , Miocardite/virologia , Adolescente , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , COVID-19/fisiopatologia , COVID-19/virologia , Criança , Pré-Escolar , Exantema , Feminino , Humanos , Inflamação/virologia , Masculino , Miocardite/metabolismo , Miocardite/patologia , Miocardite/fisiopatologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/patologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Função Ventricular Esquerda
16.
Front Immunol ; 12: 624703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692798

RESUMO

Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.


Assuntos
Doenças Autoimunes/metabolismo , Autoimunidade , Cardiomiopatias/metabolismo , Mediadores da Inflamação/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Tenascina/metabolismo , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Microambiente Celular , Humanos , Miocardite/imunologia , Miocardite/patologia , Miocárdio/imunologia , Miocárdio/patologia , Tolerância a Antígenos Próprios , Transdução de Sinais
18.
J Clin Invest ; 131(5)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645548

RESUMO

Immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers, including malignancies once considered untreatable. These agents, however, are associated with inflammation and tissue damage in multiple organs. Myocarditis has emerged as a serious ICI-associated toxicity, because, while seemingly infrequent, it is often fulminant and lethal. The underlying basis of ICI-associated myocarditis is not completely understood. While the importance of T cells is clear, the inciting antigens, why they are recognized, and the mechanisms leading to cardiac cell injury remain poorly characterized. These issues underscore the need for basic and clinical studies to define pathogenesis, identify predictive biomarkers, improve diagnostic strategies, and develop effective treatments. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems.


Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/imunologia , Biomarcadores , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Miocardite/diagnóstico , Miocardite/patologia
19.
Int J Mol Sci ; 22(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672153

RESUMO

Cardiac macrophages are known from various activities, therefore we presume that microRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myocardial remodeling in individuals with metabolic syndrome (MetS). We aim to assess the cardiac macrophage miRNA profile by selecting those miRNA molecules that potentially exhibit regulatory functions in MetS-related cardiac remodeling. Cardiac tissue macrophages from control and db/db mice (an animal model of MetS) were counted and sorted with flow cytometry, which yielded two populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Total RNA was then isolated, and miRNA expression profiles were evaluated with Next Generation Sequencing. We successfully sequenced 1400 miRNAs in both macrophage populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Among the 1400 miRNAs, about 150 showed different expression levels in control and db/db mice and between these two subpopulations. At least 15 miRNAs are possibly associated with MetS pathology in cardiac tissue due to direct or indirect regulation of the expression of miRNAs for proteins involved in angiogenesis, fibrosis, or inflammation. In this paper, for the first time we describe the miRNA transcription profile in two distinct macrophage populations in MetS-affected cardiac tissue. Although the results are preliminary, the presented data provide a foundation for further studies on intercellular cross-talk/molecular mechanism(s) involved in the regulation of MetS-related cardiac remodeling.


Assuntos
Macrófagos/fisiologia , Síndrome Metabólica/fisiopatologia , MicroRNAs/genética , Remodelação Ventricular/genética , Animais , Fibrose , Expressão Gênica , Hiperglicemia/genética , Macrófagos/patologia , Síndrome Metabólica/genética , Camundongos Endogâmicos C57BL , Camundongos Obesos , Miocardite/etiologia , Miocardite/genética , Miocardite/patologia , Miocárdio/patologia
20.
J Cardiovasc Pharmacol Ther ; 26(3): 217-224, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33703938

RESUMO

The SARS-CoV-2 virus has resulted in over 88 million cases worldwide of COVID-19 as of January 2021. The heart is one of the most commonly affected organs in COVID-19, but the nature and extent of the cardiac pathology has remained controversial. It has been shown that patients infected with SARS-CoV-2 can sustain type 1 myocardial infarction in the absence of significant atherosclerotic coronary artery disease. However, many patients present with small elevations of troponin enzymes of unclear etiology which correlate with overall COVID-19 disease outcome. Early autopsy reports indicated variable levels of typical lymphocytic myocarditis, while radiology reports have indicated that myocarditis can be a persistent problem after recovery from acute illness, raising concern about participation in college athletics. In this communication, we review the literature to date regarding the gross and microscopic findings of COVID-19 cardiac involvement, present the findings from over 40 cases from our academic medical center, and propose mechanisms by which patients develop small elevations in troponin. .


Assuntos
COVID-19/patologia , Coração/fisiopatologia , Enzima de Conversão de Angiotensina 2/metabolismo , Comorbidade , Diagnóstico por Imagem , Humanos , Mediadores da Inflamação/metabolismo , Infarto do Miocárdio/patologia , Miocardite/patologia , SARS-CoV-2 , Troponina/biossíntese
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