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2.
Viruses ; 14(2)2022 01 31.
Article in English | MEDLINE | ID: covidwho-1715767

ABSTRACT

INTRODUCTION: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. RESULTS: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3-12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. CONCLUSION: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.


Subject(s)
Herpesvirus 6, Human/physiology , Immunosuppressive Agents/administration & dosage , Myocarditis/drug therapy , Myocarditis/virology , Roseolovirus Infections/drug therapy , Roseolovirus Infections/virology , Steroids/administration & dosage , Adult , Aged , Biopsy , Cohort Studies , DNA, Viral/genetics , Female , Gene Dosage , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Humans , Male , Middle Aged , Myocarditis/immunology , Myocarditis/physiopathology , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Roseolovirus Infections/immunology , Roseolovirus Infections/physiopathology , Stroke Volume
3.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
5.
EBioMedicine ; 75: 103807, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611695

ABSTRACT

BACKGROUND: COVID-19 mRNA vaccines have proven to be highly safe and effective. Myocarditis is an adverse event associated with mRNA vaccination, especially in young male subjects. These events are rare and, in the majority of cases, resolve quickly. As myocarditis can be driven by autoimmune responses, we wanted to determine if the SARS-CoV-2 spike protein antigen encoded in the mRNA COVID vaccines had potential cross-reactivity with auto-antigens previously associated with myocarditis. METHODS: We performed a sequence identity comparison between SARS-CoV-2 spike protein-derived peptides and myocarditis-associated antigens. We also performed a structural analysis of these antigens and the SARS-CoV-2 spike protein to identify potential discontinuous 3-D epitope similarities. FINDINGS: We found no significant enrichment in the frequency of spike-derived peptides similar to myocarditis-associated antigens as compared to several controls. INTERPRETATION: Our results do not support the notion that increased occurrence of myocarditis after SARS-CoV-2-spike vaccination is mediated by a cross-reactive adaptive immune response.


Subject(s)
Antigens/genetics , COVID-19/genetics , Epitopes/genetics , Myocarditis/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Adaptive Immunity , Antigens/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cross Reactions , Epitopes/immunology , Humans , Myocarditis/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
6.
Front Immunol ; 12: 779026, 2021.
Article in English | MEDLINE | ID: covidwho-1581330

ABSTRACT

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.


Subject(s)
COVID-19/complications , Myocarditis/pathology , Myocarditis/virology , Systemic Inflammatory Response Syndrome/pathology , T-Lymphocytes/immunology , Adult , COVID-19/immunology , COVID-19/pathology , Humans , Male , Myocarditis/immunology , RNA, Viral/analysis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/immunology
7.
Biomolecules ; 11(10)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1480575

ABSTRACT

BACKGROUND: Acute myocarditis often progresses to heart failure because there is no effective, etiology-targeted therapy of this disease. Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases' (MMPs) activity. The study was designed to determine whether simvastatin inhibits MMPs activity, decreases the severity of inflammation and contractile dysfunction of the heart in experimental autoimmune myocarditis (EAM). METHODS: Simvastatin (3 or 30 mg/kg/day) was given to experimental rats with EAM by gastric gavage for 21 days. Then transthoracic echocardiography was performed, MMPs activity and troponin I level were determined and tissue samples were assessed under a light and transmission electron microscope. RESULTS: Hearts treated with simvastatin did not show left ventricular enlargement. As a result of EAM, there was an enhanced activation of MMP-9, which was significantly reduced in the high-dose simvastatin group compared to the low-dose group. It was accompanied by prevention of myofilaments degradation and reduction of severity of inflammation. CONCLUSIONS: The cardioprotective effects of simvastatin in the acute phase of EAM are, at least in part, due to its ability to decrease MMP-9 activity and subsequent decline in myofilaments degradation and suppression of inflammation. These effects were achieved in doses equivalent to therapeutic doses in humans.


Subject(s)
Inflammation/drug therapy , Metalloproteases/genetics , Myocarditis/drug therapy , Simvastatin/pharmacology , Animals , Autoimmune Diseases/drug therapy , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Cardiotonic Agents/pharmacology , Echocardiography , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Inflammation/genetics , Inflammation/immunology , Inflammation/pathology , Metalloproteases/antagonists & inhibitors , Models, Animal , Myocarditis/genetics , Myocarditis/immunology , Myocarditis/pathology , Rats , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/prevention & control
8.
Cardiovasc Res ; 117(13): 2610-2623, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1450387

ABSTRACT

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.


Subject(s)
COVID-19/virology , Cardiomyopathy, Dilated/virology , Myocarditis/virology , Parvoviridae Infections/virology , Parvovirus B19, Human/pathogenicity , SARS-CoV-2/pathogenicity , Animals , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , COVID-19/therapy , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/immunology , Cardiomyopathy, Dilated/therapy , Genetic Therapy , Host-Pathogen Interactions , Humans , Myocarditis/diagnosis , Myocarditis/immunology , Myocarditis/therapy , Parvoviridae Infections/diagnosis , Parvoviridae Infections/immunology , Parvoviridae Infections/therapy , Parvovirus B19, Human/immunology , SARS-CoV-2/immunology
9.
Curr Oncol Rep ; 23(7): 79, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1384599

ABSTRACT

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher. RECENT FINDINGS: Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes. Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.


Subject(s)
Atherosclerosis/diagnosis , Cardiotoxicity/diagnosis , Immune Checkpoint Inhibitors/therapeutic use , Myocarditis/diagnosis , Neoplasms/drug therapy , Atherosclerosis/chemically induced , Atherosclerosis/immunology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Cardiotoxicity/etiology , Cardiotoxicity/immunology , Humans , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/immunology , Myocarditis/chemically induced , Myocarditis/immunology , Neoplasms/immunology , Pandemics , Risk Factors , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
10.
Circulation ; 144(6): 471-484, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1365256

ABSTRACT

Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.


Subject(s)
Autoantigens/immunology , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Myocarditis/chemically induced , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Biomarkers , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Female , Humans , Male , Molecular Mimicry/immunology , Myocarditis/immunology , Sex Factors
11.
Pacing Clin Electrophysiol ; 44(3): 552-556, 2021 03.
Article in English | MEDLINE | ID: covidwho-1358629

ABSTRACT

We present, to our knowledge, the first case of immunosuppressive therapy (IST) application in a 12-year-old child with arrhythmogenic inflammatory cardiomyopathy resulting from the overlap between autoimmune myocarditis and primary arrhythmogenic cardiomyopathy. Indication to off-lable IST was compelling, because of recurrent drug-refractory ventricular arrhythmias (VAs). We show that IST was feasible, safe, and effective on multiple clinical endpoints, including symptoms, VA recurrences, and T-troponin release. Remarkably, all diagnostic and therapeutic strategies were worked out by a dedicated multidisciplinary team, including specialized pediatric immunologists.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/drug therapy , Arrhythmogenic Right Ventricular Dysplasia/immunology , Azathioprine/therapeutic use , Biomarkers/blood , Child , Echocardiography , Electrocardiography , Humans , Magnetic Resonance Imaging , Male , Myocarditis/drug therapy , Myocarditis/immunology , Prednisone/therapeutic use , Recurrence , Risk Factors
12.
Front Immunol ; 12: 624703, 2021.
Article in English | MEDLINE | ID: covidwho-1354863

ABSTRACT

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.


Subject(s)
Autoimmune Diseases/metabolism , Autoimmunity , Cardiomyopathies/metabolism , Inflammation Mediators/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Tenascin/metabolism , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Cardiomyopathies/immunology , Cardiomyopathies/pathology , Cellular Microenvironment , Humans , Myocarditis/immunology , Myocarditis/pathology , Myocardium/immunology , Myocardium/pathology , Self Tolerance , Signal Transduction
13.
Cardiovasc Pathol ; 54: 107361, 2021.
Article in English | MEDLINE | ID: covidwho-1281392

ABSTRACT

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.


Subject(s)
Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , COVID-19/immunology , Macrophages/immunology , Myocarditis/immunology , Myocardium/immunology , Adult , Aged , Autopsy , Biomarkers/analysis , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Female , Host-Pathogen Interactions , Humans , Immunohistochemistry , Macrophages/virology , Male , Middle Aged , Myocarditis/mortality , Myocarditis/pathology , Myocarditis/virology , Myocardium/pathology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
14.
Cells ; 10(5)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1274611

ABSTRACT

Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host's immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.


Subject(s)
Myocarditis/immunology , Th17 Cells/metabolism , Virus Diseases/immunology , Adenoviridae , Animals , Autoimmune Diseases/immunology , Chikungunya virus , Cytokines/immunology , Dengue Virus , Humans , Immune System , Immunosuppressive Agents/pharmacology , Inflammation , Interleukin-10/biosynthesis , Lymphocytes/cytology , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/virology , Myocarditis/metabolism , Myocarditis/virology , Orthomyxoviridae , SARS-CoV-2 , Simplexvirus , Th1 Cells/cytology , Th2 Cells/cytology , Virus Diseases/drug therapy , Virus Diseases/metabolism , Zika Virus
16.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-1059326

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a lethal pandemic that has claimed millions of lives worldwide. While respiratory involvement is the most common and most virulent manifestation of COVID-19, there is enough data to suggest that myocardial injury reflected through elevated troponin levels is seen in around 7-28% of patients and is related with increased morbidity and mortality.


Subject(s)
Coronavirus Infections/physiopathology , Heart/virology , Myocarditis/physiopathology , Myocardium/pathology , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Myocarditis/etiology , Myocarditis/immunology , Myocarditis/pathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2
17.
Eur Rev Med Pharmacol Sci ; 24(23): 12527-12535, 2020 12.
Article in English | MEDLINE | ID: covidwho-995013

ABSTRACT

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Myocarditis/immunology , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antioxidants/therapeutic use , Apoptosis , Atrial Natriuretic Factor/therapeutic use , Azetidines/therapeutic use , Benzyl Compounds/therapeutic use , Cytokine Release Syndrome/drug therapy , Enzyme Inhibitors/therapeutic use , Glucocorticoids/therapeutic use , Glycoproteins/therapeutic use , Humans , Hypoxia/metabolism , Hypoxia/therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Myocardial Ischemia/metabolism , Myocarditis/metabolism , Myocarditis/therapy , Myocytes, Cardiac/metabolism , Oxidative Stress , Oxygen Inhalation Therapy , Respiration, Artificial , SARS-CoV-2 , Sphingosine 1 Phosphate Receptor Modulators/therapeutic use , Trypsin Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/therapeutic use , alpha-Methyltyrosine/therapeutic use
18.
Trends Endocrinol Metab ; 31(12): 893-904, 2020 12.
Article in English | MEDLINE | ID: covidwho-867128

ABSTRACT

Coronavirus disease 2019 (COVID-19) patients with pre-existing cardiovascular disease (CVD) or with cardiovascular complications have a higher risk of mortality. The main cardiovascular complications of COVID-19 include acute cardiac injury, acute myocardial infarction (AMI), myocarditis, arrhythmia, heart failure, shock, and venous thromboembolism (VTE)/pulmonary embolism (PE). COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch. We systematically review cardiovascular manifestations, histopathology, and mechanisms of COVID-19, to help to formulate future research goals and facilitate the development of therapeutic management strategies.


Subject(s)
COVID-19/physiopathology , Cardiovascular Diseases/physiopathology , Angiotensin-Converting Enzyme 2/metabolism , Arrhythmias, Cardiac/immunology , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , COVID-19/immunology , COVID-19/metabolism , Cardiovascular Diseases/immunology , Cardiovascular Diseases/metabolism , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/physiopathology , Heart Diseases/immunology , Heart Diseases/metabolism , Heart Diseases/physiopathology , Heart Failure/immunology , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Hypoxia/immunology , Hypoxia/metabolism , Hypoxia/physiopathology , Myocardial Infarction/immunology , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Myocarditis/immunology , Myocarditis/metabolism , Myocarditis/physiopathology , Pulmonary Embolism/immunology , Pulmonary Embolism/metabolism , Pulmonary Embolism/physiopathology , Renin-Angiotensin System/physiology , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Shock/immunology , Shock/metabolism , Shock/physiopathology , Troponin/metabolism , Venous Thromboembolism/immunology , Venous Thromboembolism/metabolism , Venous Thromboembolism/physiopathology
19.
Nat Rev Cardiol ; 18(3): 169-193, 2021 03.
Article in English | MEDLINE | ID: covidwho-851285

ABSTRACT

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.


Subject(s)
Cardiomyopathies/physiopathology , Inflammation/physiopathology , Myocarditis/physiopathology , Virus Diseases/physiopathology , Animals , Antiviral Agents/therapeutic use , Autoimmunity/immunology , Biopsy , COVID-19/physiopathology , COVID-19/therapy , Cardiomyopathies/diagnosis , Cardiomyopathies/immunology , Cardiomyopathies/therapy , Cardiomyopathy, Dilated , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Coxsackievirus Infections/immunology , Coxsackievirus Infections/physiopathology , Coxsackievirus Infections/therapy , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/physiopathology , Cytomegalovirus Infections/therapy , Disease Models, Animal , Echovirus Infections/immunology , Echovirus Infections/physiopathology , Echovirus Infections/therapy , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/physiopathology , Epstein-Barr Virus Infections/therapy , Erythema Infectiosum/immunology , Erythema Infectiosum/physiopathology , Erythema Infectiosum/therapy , HIV Infections/physiopathology , Hepatitis C/immunology , Hepatitis C/physiopathology , Hepatitis C/therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Inflammation/diagnosis , Inflammation/immunology , Inflammation/therapy , Influenza, Human/immunology , Influenza, Human/physiopathology , Influenza, Human/therapy , Leukocytes/immunology , Myocarditis/diagnosis , Myocarditis/immunology , Myocarditis/therapy , Myocardium/pathology , Prognosis , Roseolovirus Infections/immunology , Roseolovirus Infections/physiopathology
20.
Front Immunol ; 11: 2055, 2020.
Article in English | MEDLINE | ID: covidwho-807548

ABSTRACT

The clinical and laboratory features of COVID-19 are reviewed with attention to the immunologic manifestations of the disease. Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis. A common theme amongst multiple reports suggests an overexuberant autoimmune component of the disease but a common pathophysiology to explain the variations in clinical presentation has been elusive. Review of the basic science of other viral induced autoimmune disorders may give clues as to why immunosuppressive and immunomodulating regimens now appear to have some efficacy in COVID-19. Review of the immunopathology also reveals other therapies that have yet to be explored. There is potential use of T cell depleting therapies and possibly anti-CD20 therapy for COVID-19 and clinical research using these medications is warranted.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections , Immunosuppressive Agents/therapeutic use , Lymphocyte Depletion , Pandemics , Pneumonia, Viral , Systemic Inflammatory Response Syndrome , T-Lymphocytes , COVID-19 , Child , Child, Preschool , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Humans , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/virology , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/therapy , Mucocutaneous Lymph Node Syndrome/virology , Myocarditis/immunology , Myocarditis/therapy , Myocarditis/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy , Systemic Inflammatory Response Syndrome/virology , T-Lymphocytes/immunology , T-Lymphocytes/pathology
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