key: cord-0730058-8p13kr49 authors: Haryalchi, Katayoun; Olangian‐Tehrani, Sepehr; Asgari Galebin, Seyed Mohammad; Mansour‐Ghanaie, Mandana title: The importance of myocarditis in Covid‐19 date: 2022-01-13 journal: Health Sci Rep DOI: 10.1002/hsr2.488 sha: 91c4dbb0bb8b69f3d289ddb61a97643cbfa66cad doc_id: 730058 cord_uid: 8p13kr49 BACKGROUND: The outbreak of Covid‐19 is a real threat to public health. It causes cardiovascular complications such as acute myocardial injury and myocarditis. Symptoms of myocarditis vary from chest pain, tachycardia, or chest tightness. Inotropes and/or vasopressors and mechanical ventilation are the protocols for cardiogenic shock in patients with myocarditis. Some previous studies stated that the mechanism of cardiac injury is not well defined but, it can be due to direct myocardial infection, respiratory failure or hypoxemia, and indirect injury from systemic inflammatory response separately or all three factors together. The pathologic processes included direct myocardial injury by virus binding to ACE2, systemic inflammation, altered myocardial demand‐supply ratio, and plaque and coronary thrombosis. There are disagreements on the usage of corticosteroids in active‐infection myocarditis. As everyday new complications of Covid‐19 appear, there is a need for further research to overcome them. AIMS: This narrative study aimed to assess the effect of Covid‐19 on myocarditis. Nowadays Covid-19 has been known as a pandemic which caused mortality and morbidity. In addition to respiratory problems, it could be accompanied by other dangerous complications. 1 One of the important ones is cardiovascular complications. And one of the serious complications is acute myocardial injury that leads to myocarditis. Also, Acute Respiratory Distress Syndrome (ARDS) can cause acute myocardial injury followed by myocarditis. As it has been shown that cardiovascular complications are associated with more mortality rate. Overall, myocardial involvement occurs in 20%-30% of hospitalized patients with Covid-19. The prevalence of myocarditis is unknown, and the number of autopsies is limited. [2] [3] [4] Maybe cardiovascular diseases and older age are risk factors for the development and severity of Covid-19. And conversely cardiovascular disease may be caused by exacerbation of Covid- 19 . It has been reported that viral myocarditis created with Covid-19 can exist without clinical symptoms. 5 Acute cardiac injury defined as elevated cardiac troponin levels and associated with higher mortality. 6 Pathology is usually focal within myocarditis, but in addition to myocardial involvement and myocarditis there is a risk of arrhythmia, fulminant heart failure, and cardiogenic shock. 7 Endomyocardial biopsy is the gold standard of myocarditis diagnosis. 8 Generally, myocarditis is an inflammatory disease. It can be intensified by cytokine storm syndrome that leads to T-Lymphocyte activation and inflammatory cytokines release. 9 Covid-19 attaches to Angiotensin-Converting Enzyme 2 (ACE2) in alveolar and myocardial tissues and causes myocardial injury. 10 It has been presented that cardiac troponin levels are high in Covid-19 obviously. 11 It is the indicator of myocardial injury even in the nonischemic myocardial process. 12 Also, the troponin T (TnT) prognostic accuracy can be increased by N-terminal pro-Btype natriuretic peptide (NT-proBNP) measurement. 13 Some previous studies stated that the mechanism of cardiac injury is not well defined but it can be due to direct myocardial infection, respiratory failure or hypoxemia, indirect injury from systemic inflammatory response separately or all three factors. 1, 14 The pathologic processes included direct myocardial injury with virus binding to ACE2, systemic inflammation, altered myocardial demand-supply ratio, plaque, and coronary thrombosis 15, 16 (Figure 1 ). As Covid-19 is a new problem as a pandemic and in fact, little is known about it. We decided to arrange this narrative review to assess the effect of Covid-19 on cardiovascular system and creating myocarditis, which can be both a cause of mortality and can lead to morbidity. We know there is a long way to go to understand all the side effects of the Covid-19, but we tried to highlight specially myocarditis caused by this disease by reviewing these few articles. This narrative study aimed to assess the effect of Covid-19 on creating myocarditis. Some of cardiac problems included acute coronary syndrome (ACS), cardiac dysfunction, blood pressure fluctuations, arrhythmias, and myocarditis. 17, 18 Although viral myocarditis created by Covid-19 can be asymptomatic, or mild to severe symptoms can be presented too. 19 Myocardial injury is defined as increased cardiac troponin above the 99th percentile. 25 The virus initially attacks cardiac cells directly and following the inflammatory response, further damage. 1, 25 Although the mechanism of cardiac injury in Covid-19 is not well defined, acute F I G U R E 1 Some of the proposed mechanisms and pathologic processes of cardiac injury in Covid-19 infection myocardial injury is the main cardiovascular complication in this pandemic. The probable mechanism is as below: • Direct myocardial injury by binding to ACE2. • Indirect myocardial injury by (a) overwhelming immuneinflammatory response (b) severe hypoxia from acute respiratory damage which leading to oxidative stress and increases the cardiometabolic demand and finally myocardial injury. • Elevation of cardiac biomarkers particularly cardiac troponin (hstroponin) and/or creatinine kinase MB that is common in Covid-19 infection. 5, 20 In Covid-19, three types of myocardial injury are included: Mild increase in troponin level is the most common type (typically more than 99%). Progressive type is the second one. In this type, some patients have normal or moderately increased troponin level. Early moderate increase in troponin level is the third one that usually occurs in clinical myocarditis. 6 Colchicine in pericarditis. 19 Rali et al pointed to the role of cytokine storm myocardial damage and proposed Tocilizumab to treat this complication. They also pointed out the role of ACE2 downregulation in Covid-19. Thus, they suggested ACE2 inhibitors to control mortality. 9 Kang et al concluded that there is no proven remedy for Covid-19, but they focused on supportive therapy. They suggested medication in the following manner: 1. Prophylactic anticoagulant therapy (to prevent thromboembolism). 3. Angiotensin receptor blockers. They prescribed Antimalarial agents like Chloroquine and Hydroxychloroquine as Covid-19 inhibitors. They also used immunoglobulins and anti-IL6 antibodies for viral neutralization and immunomodulation. It seems that IVIG terminates the inflammation suppression and alleviates hyper-inflammation phase severity. They administered corticosteroids as well. They used cell-based therapy for skeletal myoblasts, bone marrow, and mesenchymal stem cell stimulation. 1 Blockers increased ACE2 levels that may decompensate cardiac function due to Covid-19 infection. They were unsure about using antiviral remedies such as Chloroquine and Hydroxychloroquine or Azithromycin because of their cardiovascular complications like QT interval prolongation, Atrioventricular block, pulmonary hypertension, sick sinus syndrome, and sudden death. 22 Everaert et al assessed the usage of Hydroxychloroquine or Chloroquine with or without Azithromycin as the first-line treatment because of the risk of QT interval prolongation and subsequent arrhythmias. 28 Paul et al treated a case of myocarditis with 5 mg of Ramipril and 5 mg of bisoprolol. 29 Kow and Hasan discussed the usage of corticosteroid and IVIG in fulminant myocarditis. They were worried about a secondary infection that may occur by corticosteroids. They believed that IV IG was stronger in the treatment of myocarditis than corticosteroids. They illustrated that IVIG reduced in-hospital mortality significantly. It has been presented that IVIG decreased cardiac inflammation and downregulation of cytokines which has a negative inotropic effect. 30 We know that Covid-19 has confused the whole world, and myocarditis is a dangerous complication of Covid-19. There is not much information about its treatment or outcome yet. In this article, we have tried to take a brief look at 31 articles which have studied the cardiac complications of Covid-19, especially myocarditis. Because Covid-19 and its side effects as myocarditis are very new to the world there is a need for further research to overcome them. The authors thank all those who helped them writing this article. None. The importance of happy hypoxemia in COVID-19 COVID-19 cardiac injury: implications for long-term surveillance and outcomes in survivors Approach to acute cardiovascular complications in COVID-19 infection Global evaluation of echocardiography in patients with COVID-19 Myocardial injury in COVID-19 patients (The beginning or the end?) A review of acute myocardial injury in coronavirus disease 2019 Recognizing COVID-19 related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management Fulminant myocarditis and COVID19 Mechanisms of myocardial injury in Coronavirus Disease COVID-19 and acute heart failure: screening the critically I11-A position statement of the cardiac society of Australia and New Zealand (CSANZ) Cardiovascular system and COVID-19: perspectives from a developing country COVID-19 pandemic and troponin: indirect myocardial injury, myocardial inflammation or myocarditis? Suspected myocardial injury in patients with COVID-19: evidence from front line clinical observation in Wuhan, China Cardiac manifestations in COVID-19 patients-A systematic review Myocardial injury and COVID-19: possible mechanisms Two cases of coronavirus 2019-related cardiomyopathy in pregnancy COVID-19 illness and heart failure Cardiovascular complications of COVID-19: pharmacotherapy perspective. Cardiovasc Drugs Ther Fatal eosinophilic myocarditis in a healthy 17 year old male with sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2c) Spectrum of cardiac involvement in COVID-19 Cardiovigilance in COVID-19 Cardiovascular manifestations and treatment considerations in COVID-19 Special Article -Acute myocardial injury in patients hospitalized with COVID-19 infection: a review COVID-19 pandemic: cardiovascular complications and future implications COVID-19 and the heart: an update for clinicians COVID-19 "fulminant myocarditis" successfully treated with temporary mechanical circulatory support Emerging cardiological issues during the COVID-19 pandemic Myocarditis revealing COVID-19 infection in a young patient Glucocorticoid versus immunoglobulin in the treatment of COVID-19-associated fulminant myocarditis The importance of myocarditis in Covid-19 The authors report no conflict of interest regarding publication of this paper. All the authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported, and no important aspects of the study have been omitted. Related data of this project are available on request. https://orcid.org/0000-0001-8012-9952Sepehr Olangian-Tehrani https://orcid.org/0000-0002-8970-9344Seyed Mohammad Asgari Galebin https://orcid.org/0000-0002- Mandana Mansour-Ghanaie https://orcid.org/0000-0003-1503-3502