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Evidence Based Medicine
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Clinical Trials
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VisualWikitext

Revision as of 17:54, 22 July 2020

For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
For COVID-19 patient information, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mounika Reddy Vadiyala, M.B.B.S.[2]

Synonyms and keywords: Novel coronavirus, COVID-19, Wuhan coronavirus, coronavirus disease-19, coronavirus disease 2019, SARS-CoV-2, COVID-19, COVID-19, 2019-nCoV, 2019 novel coronavirus, cardiovascular finding in COVID-19, myocardial injury in COVID-19, myocarditis, myocarditis in COVID-19, COVID-19-associated myocarditis, SARS-CoV2-associated myocarditis, myocardial injury in COVID-19, COVID-19 myocarditis

Overview

COVID-19 caused by the novel coronavirus, also known as SARS-CoV-2 mainly affects the lungs, causing severe acute respiratory syndrome (SARS). It invades through the angiotensin-converting enzyme 2 (ACE2) receptors present abundantly not only in the lungs but also in the heart, kidneys, intestine, brain, skin thus causing multiorgan dysfunction. Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions. Myocardial injury is relatively common in patients with COVID-19, accounting for 7%-23% of cases, and is associated with a higher rate of morbidity and mortality. Myocarditis is a potentially lethal complication of COVID-19. Although many anecdotal reports of myocarditis have been noted, there are only a handful of case reports in the literature about myocarditis related to COVID-19. The exact pathophysiology of COVID-19-associated myocarditis is still elusive; but the proposed mechanisms involve direct invasion through ACE2 receptors and cytokine storm. If untreated, it may lead to life-threatening complications such as cardiogenic shock, heart failure and even death. Supportive care remains the mainstay of treatment.

Historical Perspective

The novel coronavirus, SARS-CoV-2, is identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in late December 2019. It was named SARS-CoV-2 for its similarity severe acute respiratory syndrome related coronaviruses such as SARS-CoV, which caused acute respiratory distress syndrome (ARDS) in 2002–2003.^[1]^[2]
On January 30, 2020,the World Health Organization(WHO) declared the outbreak as a Public Health Emergency of International Concern.
On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
On March 27, 2020, Inciardi et al., from Italy, reported the first case of acute myocardial inflammation in a patient with COVID-19.^[3]

Classification

There is no established system for the classification of the myocarditis seen in COVID-19.
For general classification of myocarditis, click here.

Pathophysiology

Myocarditis is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause.^[4]
The major cause of myocarditis in the United States and other developed countries is viral.^[5] ^[6]
The exact mechanisms of COVID-19 induced myocarditis are not yet well known, although several have been proposed based on the limited data outside of case reports.

Proposed pathophysiologies of SARS-CoV-2 myocarditis

Direct invasion of the virus into cardiomyocytes:
- COVID-19 infection is caused by receptor-mediated endocytosis via binding of the viral surface spike protein (primed by TMPRSS2 - Transmembrane Protease Serine 2) to the human angiotensin-converting enzyme 2 (ACE2) receptor.^[7]^[8]
- ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry.^[9]
- ACE2 is highly expressed in the heart as well.^[10]
- However, there are limited reports showing pathological evidence that COVID-19 directly invades the heart.^[11]

Hyperinflammation and Cytokine storm
- Naive T lymphocytes can be primed for viral antigens via antigen-presenting cells.^[12]
- The primed CD8+ T lymphocytes migrate to the cardiomyocytes and through cell-mediated cytotoxicity, cause myocardial inflammation and cardio-tropism by heart-produced Hepatocyte Growth Factor (HGF) which interacts with c-Met, an HGF receptor on naïve T lymphocytes.^[12]
- In the cytokine storm syndrome, proinflammatory cytokines such as Interleukin-6 (IL-6) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines.^[13]
- Cytokine storms result in increased vascular wall permeabilityand myocardial edema.^[14]^[15]
- A positive feedback loop of immune activation and myocardial damage is established.^[16]^[4]
- Thus cytokine storm activated by T helper cells (Th1 and Th2) and a systemic hyperinflammatory response is triggered.^[17]^[18]

Pathological changes in the myocardium

They could be due to viral replication in the myocardium or immune responses caused by the infection or due to systemic responses to respiratory failure.
Interstitial mononuclear inflammatory infiltration has been observed in the heart tissue in COVID-19 autopsy studies.^[19]
In one of the autopsy studies of myocarditis in COVID-19, the viral particles were observed in interstitial cytopathic macrophages. Cardiac myocytes showed non‐specific features consisting of focal myofibrillar lysis, and lipid droplets but no viral particles in myocytes and endothelia; small intramural vessels were free from vasculitis and thrombosis.^[11]

Light microscopy immunostaining of the inflammatory infiltrate. (A,B) Low‐ and high‐power views of endomyocardial biopsy, with sparse CD45RO positive interstitial cells. (C,D) Large, vacuolated macrophages immunostained with anti‐CD68 antibodies. (E) Ultrastructural morphology of a large and cytopathic macrophage. (*A–D*: the bar scale is in the left low corner of each panel. E: the bar scale is in the right low corner of the panel and corresponds to 2 μm). Case courtesy by Guido Tavazzi^[20]

Causes

Myocarditis in COVID-19 is caused by:

Direct invasion of endothelial cells by SARS-CoV-2
Pro-inflammatory cytokine storm

Differentiating COVID-19 associated myocarditis from other Diseases

Myocarditis in COVID-19 must be differentiated from other diseases that cause chest pain, dyspnea, elevated cardiac biomarkers, ventricular dysfunction, such as:

Acute Coronary Syndrome
Stress-induced cardiomyopathy (Takotsubo cardiomyopathy)
Heart failure
Heart failure

For further information about the differential diagnosis, click here.
For further information about the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

The prevalence of cardiovascular disease among patients with COVID-19 is high, and >7% of patients experience myocardial injury from the infection.^[21]
The exact incidence of myocarditis among hospitalized COVID-19 patients is unknown. The overall incidence of acute cardiac injury caused by COVID-19 ranges from 7 to 28% among hospitalized patients.^[22]^[23]^[24]
The prevalence of myocarditis among COVID-19 patients has not yet been reported. Though many anecdotal reports of myocarditis have been noted, there are only a few case reports of myocarditis related to COVID-19.^[23]^[15]^[3]^[14]^[25]^[26]^[11]^[27]^[28]^[29]
Myocarditis has also been reported as the cause of death in some COVID-19 patients.^[30]

Age

COVID-19-associated myocarditis is more commonly observed among elderly patients.^[23]^[24]

Gender

There is no data on gender predilection to myocarditis in COVID-19.

Race

There is no data on racial predilection to myocarditis in COVID-19.

Risk Factors

There are no established risk factors for myocarditis, however the prevalence of COVID-19-associated myocarditis has been more in elderly patients [age>50] and patients with pre-existing cardiovascular diseases.^[24]^[23]

Screening

There is insufficient evidence to recommend routine screening for myocarditis in COVID-19 patients.

Natural History, Complications and Prognosis

Natural history

If left untreated, myocarditis of patients with COVID-19 may progress to to cardiogenic shock, heart failure, and eventually can lead to death.^[27]

Complications

Common complications of [myocarditis] include:

Prognosis

Prognosis is generally poor.
A retrospective analysis of the cause of death in Chinese patients infected with COVID-19 revealed that 40% of patients died at least in part due to myocardial injury and circulatory collapse.^[30]
In another study, patients hospitalized for COVID-19 infection developed cardiac injury in approximately 20% of cases; thus leading to greater than 50% mortality.^[23]

Diagnosis

Diagnostic Criteria

The diagnosis of myocarditis cannot be made with a single test or examination. When indicated, the diagnosis requires a combination of:

Signs and Symptoms

Clinical presentations have varied in the reported COVID-19 cases with myocarditis in the literature with potential overlap in symptomatology in patients with primary COVID-19 infection and COVID-19 patients with clinically suspected myocarditis. Clinical presentation of COVID-19 related myocarditis varies among cases from mild to severe to fulminant.

Mild - fatigue and dyspnea, chest pain or chest tightness on exertion.^[3]^[14]^[15]^[25]
Severe - Many patients deteriorate and show symptoms of tachycardia and acute-onset heart failure with cardiogenic shock.^[15]^[3]^[14]
Patients may also present with signs of right-sided heart failure, including the following:^[6]
Fulminant - Fulminant myocarditis is defined as ventricular dysfunction and heart failure within 2–3 weeks of infection.^[4]^[31]^[26]^[32]
The early signs of fulminant myocarditis resemble those of sepsis: Fever, low pulse pressure, cold extremities, and sinus tachycardia.^[6]^[15]

According to a study, ventricular arrhythmia has also been known to occur in patients with myocarditis.^[33]

Physical Examination

Physical examination of patients with severe myocarditis may find:

Physical examination of patients with fulminant myocarditis may find:

Laboratory Findings

Inflammatory biomarkers

Elevated levels of inflammatory markers including erythrocyte sedimentation rate, C reactive protein, and procalcitonin are usually seen in myocarditis but they are not specific and do not confirm the diagnosis.
Increases levels of Interleukin-6 (IL-6), d-dimer, serum ferritin, prothrombin time were seen in COVID-19 patients.^[23]^[13]

Cardiac biomarkers

Levels of cardiac enzymes such as cardiac troponins (cardiac troponin I(cTnI) and cardiac troponin T (cTnT)) and natriuretic peptides (N-terminal pro-B-type natriuretic peptide (NT-proBNP), and Brain natriuretic peptide (BNP)) usually are elevated in myocarditis due to acute myocardial injury and possible ventricular dilation.
Elevations of both troponin and NT-proBNP levels were observed in the COVID-19–related myocarditis cases.^[15]^[3]^[14]^[25]^[31]^[34]
Elevated NT-proBNP level has been associated with worse clinical outcomes in severe COVID-19 patients.^[35]^[36]
Cardiac troponins and brain natriuretic peptides are sensitive but not specific in the diagnosis of myocarditis. It requires other supplementary findings and investigations.^[37]^[38]^[39]
Although a negative troponin result cannot exclude myocarditis, negative serial high-sensitivity cardiac troponin (hs-cTn) still is helpful in the acute phase and makes the diagnosis of acute myocarditis significantly less likely.^[40]

Electrocardiogram

ECG is usually abnormal in myocarditis but it is neither sensitive nor specific in the diagnosis.^[41]^[5]
ECG abnormalities ST-elevation and PR depression may be observed in myocarditis in COVID-19 patients.^[3]^[5]^[31]
However, these abnormalities are not sensitive in detecting myocarditis in COVID-19. For example, one COVID-19–related myocarditis case showed neither ST-elevation nor PR depression.^[15]
Other ECG abnormalities, including new-onset bundle branch block, premature ventricular complexes, QT prolongation, and bradyarrhythmia with advanced atrioventricular nodal block, can be observed in myocarditis.^[14]

The American Heart Association (AHA) recommends further testing with 1 or more cardiac imaging methods such as an echocardiogram or cardiovascular magnetic resonance imaging (CMR) for patients having signs consistent with myocarditis.^[6]
However, echocardiogram or cardiac imaging can be avoided or delayed until recovery from COVID-19 in the patients with COVID-19 and myocardial injury who are hemodynamically and electrophysiologically stable with mild to moderate elevations of troponin unless the patient clinically deteriorates and develops hemodynamic instability, shock, ventricular arrhythmias, or a severely elevated or rapidly rising troponin levels.^[42]

Echocardiography

The prominent signs of myocarditis on an echocardiogram are increased wall thickness, ventricular dilation, diffuse hypokinesia/dyskinesia, and pericardial effusion in the background of ventricular systolic dysfunction.^[43]^[44]^[5]
These findings were noted in COVID-19 related myocarditis cases.^[14]^[3]^[15]

Cardiac Magnetic Resonance

Cardiac Magnetic Resonance (CMR) imaging is a vital test in the diagnosis of myocarditis, especially if an endomyocardial biopsy (EMB) is not pursued or cannot be obtained, before the COVID-19 pandemic.^[45]
Cardiac Magnetic resonance (CMR) has major imaging advantages with highest diagnostic accuracy over echocardiography.^[46]
CMR is not indicated in unstable patients who present with severe heart failure, circulatory shock, ventricular arrhythmia, or high-grade AV block and an EMB should be obtained.^[47]
CMR using the revised Lake Louise consensus criteria to interpret the results has a specificity of up to 91% and a sensitivity of 67% for diagnosing myocarditis.^[47]
- 1) Edema
- 2) Irreversible cell injury
- 3) Hyperemia or capillary leak.
If available and there are no contraindications, CMR can safely be used as a first-line diagnostic tool in myocarditis associated with COVID-19.^[48]
In all of the COVID-19–related myocarditis cases for which CMR results were reported, myocardial edema and/or scarring were observed.^[3]^[14]^[25]^[27]^[34]^[28]

Cardiac Computed Tomography

Cardiac computed tomography scan (CT scan) with contrast enhancement and ECG gating is an effective alternative to CMR in terms of rapid testing and minimal requirement of breath-holding, especially when the patient has to undergo a high-resolution CT scan (HRCT) of the chest for assessment of acute respiratory distress syndrome.
Myocardial hypertrophy due to edema was observed in COVID-19 related myocarditis.^[14]

Endomyocardial biopsy

Endomyocardial biopsy (EMB) has been recommended as the definitive diagnostic tool for myocarditis by the American Heart Association (AHA) and European Society of Cardiology (ESC).^[49]
In non–COVID-19 cases, endomyocardial biopsy has traditionally been recommended in fulminant presentations to exclude the rare presentation of eosinophilic, hypersensitive,and giant cell myocarditis.^[50]
However, in COVID-19, it may not be feasible because of the instability of the patient, requirement of expertise, false-negative rate and risk of contagiousness, especially if the biopsy results would not change clinical management.^[5]^[6]^[46]
EMB samples if obtained should be tested for inflammatory infiltrates and for the presence of viral genomes by DNA/RNA extraction.^[5]
In a COVID-19 case reported, EMB showed diffuse T-lymphocytic inflammatory infiltrates with huge interstitial edema and no replacement fibrosis, suggesting an acute inflammatory process. SARS-CoV-2 genome was absent within the myocardium in molecular analysis.^[25]

Treatment

Medical Therapy

There is no definitive treatment for COVID-19-associated myocarditis; the mainstay of therapy is supportive care because no specific effective anti-viral therapies have been identified.
As per AHA recommendations, in the patients of fulminant myocarditis, initial management includes the protocol of cardiogenic shock which is the administration of inotropes and/vasopressors and mechanical ventilation; and use of extracorporeal membrane oxygenation(ECMO), ventricular assistive devices (VAD) in severe cases.^[15]^[51]^[31]^[3]^[26]
This protocol has been the mainstay of treatment in COVID-19-associated myocarditis cases as well and proved beneficial in mitigating ventricular systolic dysfunction.
Though the European Society of Cardiology (ESC) did not approve the use of intravenous immunoglobulins (IVIG) and corticosteroids in active-infection myocarditis, COVID-19-associated myocarditis cases have been reported in which use of immunoglobulins and corticosteroids such as methylprednisolone and hydrocortisone have been beneficial.^[26]^[15]^[3]^[34]^[27]
Tocilizumab, an anti–IL-6 receptor monoclonal antibody, is being tested in a randomized controlled trial of COVID-19 patients with raised IL-6 levels.
Tocilizumab, might be beneficial in the setting of cytokine storm syndrome and help reduce myocardial inflammation.^[40]
Although the cases of COVID-19 patients with myocarditis were treated with steroids and immunoglobulins, it is uncertain the incremental benefit these therapies might have provided over supportive care.
Further evidence is needed to determine whether any combination of immunosuppression improves outcomes among patients with myocarditis in COVID-19.

Surgery

Surgical intervention is not recommended for the management of COVID-19-associated myocarditis.

Primary Prevention

There are no established measures for the primary prevention of COVID-19-associated myocarditis.
For primary preventive measures of [COVID-19], click here.

Secondary Prevention

There are no established measures for the secondary prevention of COVID-19-associated myocarditis.
For secondary preventive measures of [COVID-19], click here.

References

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↑ ^47.0 ^47.1 Friedrich, Matthias G.; Sechtem, Udo; Schulz-Menger, Jeanette; Holmvang, Godtfred; Alakija, Pauline; Cooper, Leslie T.; White, James A.; Abdel-Aty, Hassan; Gutberlet, Matthias; Prasad, Sanjay; Aletras, Anthony; Laissy, Jean-Pierre; Paterson, Ian; Filipchuk, Neil G.; Kumar, Andreas; Pauschinger, Matthias; Liu, Peter (2009). "Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper". Journal of the American College of Cardiology. 53 (17): 1475–1487. doi:10.1016/j.jacc.2009.02.007. ISSN 0735-1097.
↑ Han, Yuchi; Chen, Tiffany; Bryant, Jennifer; Bucciarelli-Ducci, Chiara; Dyke, Christopher; Elliott, Michael D.; Ferrari, Victor A.; Friedrich, Matthias G.; Lawton, Chris; Manning, Warren J.; Ordovas, Karen; Plein, Sven; Powell, Andrew J.; Raman, Subha V.; Carr, James (2020). "Society for Cardiovascular Magnetic Resonance (SCMR) guidance for the practice of cardiovascular magnetic resonance during the COVID-19 pandemic". Journal of Cardiovascular Magnetic Resonance. 22 (1). doi:10.1186/s12968-020-00628-w. ISSN 1532-429X.
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↑ Cooper, Leslie T.; Baughman, Kenneth L.; Feldman, Arthur M.; Frustaci, Andrea; Jessup, Mariell; Kuhl, Uwe; Levine, Glenn N.; Narula, Jagat; Starling, Randall C.; Towbin, Jeffrey; Virmani, Renu (2007). "The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease". Circulation. 116 (19): 2216–2233. doi:10.1161/CIRCULATIONAHA.107.186093. ISSN 0009-7322.
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[LuCui2020-1] Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.

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[KociolCooper2020-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 Kociol, Robb D.; Cooper, Leslie T.; Fang, James C.; Moslehi, Javid J.; Pang, Peter S.; Sabe, Marwa A.; Shah, Ravi V.; Sims, Daniel B.; Thiene, Gaetano; Vardeny, Orly (2020). "Recognition and Initial Management of Fulminant Myocarditis". Circulation. 141 (6). doi:10.1161/CIR.0000000000000745. ISSN 0009-7322.

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[TavazziPellegrini2020-11] 11.0 ^11.1 ^11.2 Tavazzi, Guido; Pellegrini, Carlo; Maurelli, Marco; Belliato, Mirko; Sciutti, Fabio; Bottazzi, Andrea; Sepe, Paola Alessandra; Resasco, Tullia; Camporotondo, Rita; Bruno, Raffaele; Baldanti, Fausto; Paolucci, Stefania; Pelenghi, Stefano; Iotti, Giorgio Antonio; Mojoli, Francesco; Arbustini, Eloisa (2020). "Myocardial localization of coronavirus in COVID‐19 cardiogenic shock". European Journal of Heart Failure. 22 (5): 911–915. doi:10.1002/ejhf.1828. ISSN 1388-9842.

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[ZhouYu2020-13] 13.0 ^13.1 Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.

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[ClerkinFried2020-21] Clerkin, Kevin J.; Fried, Justin A.; Raikhelkar, Jayant; Sayer, Gabriel; Griffin, Jan M.; Masoumi, Amirali; Jain, Sneha S.; Burkhoff, Daniel; Kumaraiah, Deepa; Rabbani, LeRoy; Schwartz, Allan; Uriel, Nir (2020). "COVID-19 and Cardiovascular Disease". Circulation. 141 (20): 1648–1655. doi:10.1161/CIRCULATIONAHA.120.046941. ISSN 0009-7322.

[WangHu2020-22] Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.

[ShiQin2020-23] 23.0 ^23.1 ^23.2 ^23.3 ^23.4 ^23.5 Shi, Shaobo; Qin, Mu; Shen, Bo; Cai, Yuli; Liu, Tao; Yang, Fan; Gong, Wei; Liu, Xu; Liang, Jinjun; Zhao, Qinyan; Huang, He; Yang, Bo; Huang, Congxin (2020). "Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China". JAMA Cardiology. doi:10.1001/jamacardio.2020.0950. ISSN 2380-6583.

[GuoFan2020-24] 24.0 ^24.1 ^24.2 Guo, Tao; Fan, Yongzhen; Chen, Ming; Wu, Xiaoyan; Zhang, Lin; He, Tao; Wang, Hairong; Wan, Jing; Wang, Xinghuan; Lu, Zhibing (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. doi:10.1001/jamacardio.2020.1017. ISSN 2380-6583.

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@@ Line 79: / Line 79: @@
 ==Risk Factors==
-*There are no established risk factors for [[myocarditis]].
+*There are no established risk factors for [[myocarditis]], however the [[prevalance|prevalence]] of [[COVID-19]]-associated [[myocarditis]] has been more in [[elderly]] patients [age>50] and patients with pre-existing [[cardiovascular diseases]].<ref name="GuoFan2020">{{cite journal|last1=Guo|first1=Tao|last2=Fan|first2=Yongzhen|last3=Chen|first3=Ming|last4=Wu|first4=Xiaoyan|last5=Zhang|first5=Lin|last6=He|first6=Tao|last7=Wang|first7=Hairong|last8=Wan|first8=Jing|last9=Wang|first9=Xinghuan|last10=Lu|first10=Zhibing|title=Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1017}}</ref><ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref>
-*But the [[prevalance]] of [[COVID-19]]-associated [[myocarditis]] has been more in [[elderly]] patients [age>50] and patients with pre-existing [[cardiovascular diseases]].<ref name="GuoFan2020">{{cite journal|last1=Guo|first1=Tao|last2=Fan|first2=Yongzhen|last3=Chen|first3=Ming|last4=Wu|first4=Xiaoyan|last5=Zhang|first5=Lin|last6=He|first6=Tao|last7=Wang|first7=Hairong|last8=Wan|first8=Jing|last9=Wang|first9=Xinghuan|last10=Lu|first10=Zhibing|title=Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1017}}</ref><ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref>
 ==Screening==
@@ Line 87: / Line 86: @@
 == Natural History, Complications and Prognosis==
 ===Natural history===
-* If left untreated, [[myocarditis]] of patients with [[COVID-19]] may progress to develop [[cardiogenic shock]], [[heart failure]], and succumb to death.<ref name="CoyleIgbinomwanhia2020">{{cite journal|last1=Coyle|first1=Justin|last2=Igbinomwanhia|first2=Efehi|last3=Sanchez-Nadales|first3=Alejandro|last4=Danciu|first4=Sorin|last5=Chu|first5=Chae|last6=Shah|first6=Nishit|title=A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.025}}</ref>
+* If left untreated, [[myocarditis]] of patients with [[COVID-19]] may progress to to [[cardiogenic shock]], [[heart failure]], and eventually can lead to death.<ref name="CoyleIgbinomwanhia2020">{{cite journal|last1=Coyle|first1=Justin|last2=Igbinomwanhia|first2=Efehi|last3=Sanchez-Nadales|first3=Alejandro|last4=Danciu|first4=Sorin|last5=Chu|first5=Chae|last6=Shah|first6=Nishit|title=A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.025}}</ref>
 ===Complications===
 Common complications of [<nowiki/>[[myocarditis]]] include:
 *[[Dilated cardiomyopathy]]
 *Acute-onset [[heart failure]]
@@ Line 98: / Line 100: @@
 ===Prognosis===
 *[[Prognosis]] is generally [[poor]].
-*A [[retrospective]] analysis of the cause of death in [[Chinese]] patients infected with [[COVID-19]] revealed that 40% of patients died at least in part because of [[myocardial injury]] and [[circulatory collapse]].<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1294–1297|issn=0342-4642|doi=10.1007/s00134-020-06028-z}}</ref>
+*A [[retrospective]] analysis of the cause of death in [[Chinese]] patients infected with [[COVID-19]] revealed that 40% of patients died at least in part due to [[myocardial injury]] and [[circulatory collapse]].<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1294–1297|issn=0342-4642|doi=10.1007/s00134-020-06028-z}}</ref>
-*In another study, patients hospitalized for [[COVID-19]] infection developed [[cardiac]] injury in roughly 20% of cases; thus leading to greater than 50% [[mortality]].<ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref>
+*In another study, patients hospitalized for [[COVID-19]] infection developed [[cardiac]] injury in approximately 20% of cases; thus leading to greater than 50% [[mortality]].<ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref>
 == Diagnosis ==
@@ Line 111: / Line 113: @@
 === Signs and Symptoms ===
-Clinical presentations have varied in the reported [[COVID-19]] cases with [[myocarditis]] in the literature with potential overlap in symptomatology in patients with primary [[COVID-19]] infection and [[COVID-19]] patients with clinically suspected [[myocarditis]]. Clinical presentation of [[SARS-CoV-2]] [[myocarditis]] varies among cases from mild to severe to [[fulminant]].
+Clinical presentations have varied in the reported [[COVID-19]] cases with [[myocarditis]] in the literature with potential overlap in symptomatology in patients with primary [[COVID-19]] infection and [[COVID-19]] patients with clinically suspected [[myocarditis]]. Clinical presentation of [[COVID-19]] related [[myocarditis]] varies among cases from mild to severe to [[fulminant]].
-*Mild-[[fatigue]] and [[dyspnea]], [[chest pain]] or chest tightness on exertion.<ref name="InciardiLupi2020" /><ref name="HanKim2020" /><ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref>
+*'''Mild''' - [[fatigue]] and [[dyspnea]], [[chest pain]] or chest tightness on exertion.<ref name="InciardiLupi2020" /><ref name="HanKim2020" /><ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref>
-*Severe - Many patients deteriorate and show symptoms of [[tachycardia]] and [[heart failure|acute-onset heart failure]] with [[cardiogenic shock]].<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref>
+*'''Severe''' - Many patients deteriorate and show symptoms of [[tachycardia]] and [[heart failure|acute-onset heart failure]] with [[cardiogenic shock]].<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref>
 *Patients may also present with signs of [[heart failure|right-sided heart failure]], including the following:<ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref>
 **Raised [[jugular venous pressure]]
 **[[Right upper quadrant pain]]
 **[[Peripheral edema|Peripheral edema.]]
-*Fulminant - [[Fulminant myocarditis]] is defined as [[ventricular dysfunction]] and [[heart failure]] within 2–3 weeks of infection.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref><ref name="FangWei2020">{{cite journal|last1=Fang|first1=Yuan|last2=Wei|first2=Xin|last3=Ma|first3=Fenglian|last4=Hu|first4=Hongde|title=Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin|journal=European Heart Journal|year=2020|issn=0195-668X|doi=10.1093/eurheartj/ehaa190}}</ref><ref name="WangLi2018">{{cite journal|last1=Wang|first1=Daowen|last2=Li|first2=Sheng|last3=Jiang|first3=Jiangang|last4=Yan|first4=Jiangtao|last5=Zhao|first5=Chunxia|last6=Wang|first6=Yan|last7=Ma|first7=Yexin|last8=Zeng|first8=Hesong|last9=Guo|first9=Xiaomei|last10=Wang|first10=Hong|last11=Tang|first11=Jiarong|last12=Zuo|first12=Houjuan|last13=Lin|first13=Li|last14=Cui|first14=Guanglin|title=Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis|journal=Science China Life Sciences|volume=62|issue=2|year=2018|pages=187–202|issn=1674-7305|doi=10.1007/s11427-018-9385-3}}</ref>
+*'''Fulminant''' - [[Fulminant myocarditis]] is defined as [[ventricular dysfunction]] and [[heart failure]] within 2–3 weeks of infection.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref><ref name="FangWei2020">{{cite journal|last1=Fang|first1=Yuan|last2=Wei|first2=Xin|last3=Ma|first3=Fenglian|last4=Hu|first4=Hongde|title=Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin|journal=European Heart Journal|year=2020|issn=0195-668X|doi=10.1093/eurheartj/ehaa190}}</ref><ref name="WangLi2018">{{cite journal|last1=Wang|first1=Daowen|last2=Li|first2=Sheng|last3=Jiang|first3=Jiangang|last4=Yan|first4=Jiangtao|last5=Zhao|first5=Chunxia|last6=Wang|first6=Yan|last7=Ma|first7=Yexin|last8=Zeng|first8=Hesong|last9=Guo|first9=Xiaomei|last10=Wang|first10=Hong|last11=Tang|first11=Jiarong|last12=Zuo|first12=Houjuan|last13=Lin|first13=Li|last14=Cui|first14=Guanglin|title=Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis|journal=Science China Life Sciences|volume=62|issue=2|year=2018|pages=187–202|issn=1674-7305|doi=10.1007/s11427-018-9385-3}}</ref>
 *The early signs of fulminant myocarditis resemble those of [[sepsis]]: [[Fever]], low [[pulse pressure]], [[cold extremities]], and [[sinus tachycardia]].<ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref><ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref>
-* According to a study, [[ventricular arrhythmias]] are also seen in the patients of [[myocarditis]].<ref name="PerettoSala2020">{{cite journal|last1=Peretto|first1=Giovanni|last2=Sala|first2=Simone|last3=Rizzo|first3=Stefania|last4=Palmisano|first4=Anna|last5=Esposito|first5=Antonio|last6=De Cobelli|first6=Francesco|last7=Campochiaro|first7=Corrado|last8=De Luca|first8=Giacomo|last9=Foppoli|first9=Luca|last10=Dagna|first10=Lorenzo|last11=Thiene|first11=Gaetano|last12=Basso|first12=Cristina|last13=Della Bella|first13=Paolo|title=Ventricular Arrhythmias in Myocarditis|journal=Journal of the American College of Cardiology|volume=75|issue=9|year=2020|pages=1046–1057|issn=07351097|doi=10.1016/j.jacc.2020.01.036}}</ref>
+* According to a study, [[ventricular arrhythmias|ventricular arrhythmia]] has also been known to occur in patients with [[myocarditis]].<ref name="PerettoSala2020">{{cite journal|last1=Peretto|first1=Giovanni|last2=Sala|first2=Simone|last3=Rizzo|first3=Stefania|last4=Palmisano|first4=Anna|last5=Esposito|first5=Antonio|last6=De Cobelli|first6=Francesco|last7=Campochiaro|first7=Corrado|last8=De Luca|first8=Giacomo|last9=Foppoli|first9=Luca|last10=Dagna|first10=Lorenzo|last11=Thiene|first11=Gaetano|last12=Basso|first12=Cristina|last13=Della Bella|first13=Paolo|title=Ventricular Arrhythmias in Myocarditis|journal=Journal of the American College of Cardiology|volume=75|issue=9|year=2020|pages=1046–1057|issn=07351097|doi=10.1016/j.jacc.2020.01.036}}</ref>
 === Physical Examination ===
-*Physical examination of patients with severe [[myocarditis]] may be remarkable for:
+*Physical examination of patients with severe [[myocarditis]] may find:
 :*[[Tachycardia]]
 :*Raised [[jugular venous pressure]]
@@ Line 130: / Line 132: @@
 :*[[Peripheral edema]]
-*Physical examination of patients with [[fulminant]] [[myocarditis]] may be remarkable for:
+*Physical examination of patients with [[fulminant]] [[myocarditis]] may find:
 :*[[Fever]]
 :*[[Sinus tachycardia]]
@@ Line 170: / Line 172: @@
 **3) [[Hyperemia]] or [[capillary]] leak.
 *If available and there are no contraindications, [[Cardiovascular magnetic resonance imaging (CMR)|CMR]] can safely be used as a first-line diagnostic tool in [[myocarditis]] associated with [[COVID-19]].<ref name="HanChen2020">{{cite journal|last1=Han|first1=Yuchi|last2=Chen|first2=Tiffany|last3=Bryant|first3=Jennifer|last4=Bucciarelli-Ducci|first4=Chiara|last5=Dyke|first5=Christopher|last6=Elliott|first6=Michael D.|last7=Ferrari|first7=Victor A.|last8=Friedrich|first8=Matthias G.|last9=Lawton|first9=Chris|last10=Manning|first10=Warren J.|last11=Ordovas|first11=Karen|last12=Plein|first12=Sven|last13=Powell|first13=Andrew J.|last14=Raman|first14=Subha V.|last15=Carr|first15=James|title=Society for Cardiovascular Magnetic Resonance (SCMR) guidance for the practice of cardiovascular magnetic resonance during the COVID-19 pandemic|journal=Journal of Cardiovascular Magnetic Resonance|volume=22|issue=1|year=2020|issn=1532-429X|doi=10.1186/s12968-020-00628-w}}</ref>
-*In all of the [[SARS-CoV-2]]–related [[myocarditis]] cases for which [[Cardiovascular magnetic resonance imaging (CMR)|CMR]] results were reported, [[myocardial edema]] and/or [[scar|scarring]] were observed.<ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref><ref name="CoyleIgbinomwanhia2020">{{cite journal|last1=Coyle|first1=Justin|last2=Igbinomwanhia|first2=Efehi|last3=Sanchez-Nadales|first3=Alejandro|last4=Danciu|first4=Sorin|last5=Chu|first5=Chae|last6=Shah|first6=Nishit|title=A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.025}}</ref><ref name="DoyenMoceri2020">{{cite journal|last1=Doyen|first1=Denis|last2=Moceri|first2=Pamela|last3=Ducreux|first3=Dorothée|last4=Dellamonica|first4=Jean|title=Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes|journal=The Lancet|volume=395|issue=10235|year=2020|pages=1516|issn=01406736|doi=10.1016/S0140-6736(20)30912-0}}</ref><ref name="LuetkensIsaak2020">{{cite journal|last1=Luetkens|first1=Julian Alexander|last2=Isaak|first2=Alexander|last3=Zimmer|first3=Sebastian|last4=Nattermann|first4=Jacob|last5=Sprinkart|first5=Alois Martin|last6=Boesecke|first6=Christoph|last7=Rieke|first7=Gereon Jonas|last8=Zachoval|first8=Christian|last9=Heine|first9=Annkristin|last10=Velten|first10=Markus|last11=Duerr|first11=Georg Daniel|title=Diffuse Myocardial Inflammation in COVID-19 Associated Myocarditis Detected by Multiparametric Cardiac Magnetic Resonance Imaging|journal=Circulation: Cardiovascular Imaging|volume=13|issue=5|year=2020|issn=1941-9651|doi=10.1161/CIRCIMAGING.120.010897}}</ref>
+*In all of the [[COVID-19]]–related [[myocarditis]] cases for which [[Cardiovascular magnetic resonance imaging (CMR)|CMR]] results were reported, [[myocardial edema]] and/or [[scar|scarring]] were observed.<ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref><ref name="CoyleIgbinomwanhia2020">{{cite journal|last1=Coyle|first1=Justin|last2=Igbinomwanhia|first2=Efehi|last3=Sanchez-Nadales|first3=Alejandro|last4=Danciu|first4=Sorin|last5=Chu|first5=Chae|last6=Shah|first6=Nishit|title=A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.025}}</ref><ref name="DoyenMoceri2020">{{cite journal|last1=Doyen|first1=Denis|last2=Moceri|first2=Pamela|last3=Ducreux|first3=Dorothée|last4=Dellamonica|first4=Jean|title=Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes|journal=The Lancet|volume=395|issue=10235|year=2020|pages=1516|issn=01406736|doi=10.1016/S0140-6736(20)30912-0}}</ref><ref name="LuetkensIsaak2020">{{cite journal|last1=Luetkens|first1=Julian Alexander|last2=Isaak|first2=Alexander|last3=Zimmer|first3=Sebastian|last4=Nattermann|first4=Jacob|last5=Sprinkart|first5=Alois Martin|last6=Boesecke|first6=Christoph|last7=Rieke|first7=Gereon Jonas|last8=Zachoval|first8=Christian|last9=Heine|first9=Annkristin|last10=Velten|first10=Markus|last11=Duerr|first11=Georg Daniel|title=Diffuse Myocardial Inflammation in COVID-19 Associated Myocarditis Detected by Multiparametric Cardiac Magnetic Resonance Imaging|journal=Circulation: Cardiovascular Imaging|volume=13|issue=5|year=2020|issn=1941-9651|doi=10.1161/CIRCIMAGING.120.010897}}</ref>
 === Cardiac Computed Tomography ===
@@ Line 187: / Line 189: @@
 === Medical Therapy ===
-*There is no definitive treatment for [[COVID-19]]-assocaited [[myocarditis]]; the mainstay of therapy is supportive care because no specific effective [[Anti-viral drug|anti-viral]] therapies have been identified.
+*There is no definitive treatment for [[COVID-19]]-associated [[myocarditis]]; the mainstay of therapy is supportive care because no specific effective [[Anti-viral drug|anti-viral]] therapies have been identified.
 *As per [[American Heart Association|AHA]] recommendations, in the patients of [[fulminant myocarditis]], initial management includes the protocol of [[cardiogenic shock]] which is the administration of [[inotropes]] and/[[vasopressors]] and [[mechanical ventilation]]; and use of [[extracorporeal membrane oxygenation]]([[ECMO]]), [[ventricular assist device|ventricular assistive devices]] ([[VAD]]) in severe cases.<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="RaoSasser2014">{{cite journal|last1=Rao|first1=Sangeetha|last2=Sasser|first2=William|last3=Diaz|first3=Franco|last4=Sharma|first4=Nirmal|last5=Alten|first5=Jeffrey|title=Coronavirus Associated Fulminant Myocarditis Successfully Treated With Intravenous Immunoglobulin and Extracorporeal Membrane Oxygenation|journal=Chest|volume=146|issue=4|year=2014|pages=336A|issn=00123692|doi=10.1378/chest.1992018}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref><ref name="InciardiLupi2020" /><ref name="FangWei2020" />
 *This protocol has been the mainstay of treatment in [[COVID-19]]-associated [[myocarditis]] cases as well and proved beneficial in mitigating [[systolic dysfunction|ventricular systolic dysfunction]].