Skip to main content
The Egyptian Heart Journal
Download PDF

COVID-19 and myocarditis: a review of literature

The Egyptian Heart Journal volume 74, Article number: 23 (2022) Cite this article

Abstract

Myocarditis has been discovered to be a significant complication of coronavirus disease 2019 (COVID-19), a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 myocarditis seems to have distinct inflammatory characteristics, which make it unique to other viral etiologies. The incidence of COVID-19 myocarditis is still not clear as a wide range of figures have been quoted in the literature; however, it seems that the risk of developing myocarditis increases with more severe infection. Furthermore, the administration of the mRNA COVID-19 vaccine has been associated with the development of myocarditis, particularly after the second dose. COVID-19 myocarditis has a wide variety of presentations, ranging from dyspnea and chest pain to acute heart failure and possibly death. It is important to catch any cases of myocarditis, particularly those presenting with fulminant myocarditis which can be characterized by signs of heart failure and arrythmias. Initial work up for suspected myocarditis should include serial troponins and electrocardiograms. If myocardial damage is detected in these tests, further screening should be carried out. Cardiac magnetic resonance imagining and endomyocardial biopsy are the most useful tests for myocarditis. Treatment for COVID-19 myocarditis is still controversial; however, the use of intravenous immunoglobulins and corticosteroids in combination may be effective, particularly in cases of fulminant myocarditis. Overall, the incidence of COVID-19 myocarditis requires further research, while the use of intravenous immunoglobulins and corticosteroids in conjunction requires large randomized controlled trials to determine their efficacy.

Background

An outbreak of pneumonia infections originating in December 2019, Wuhan, China, was given the name coronavirus disease 2019 (COVID-19) [1]. The cause was discovered to be a novel virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. The virus rapidly spread across the globe and on March 11, 2020, the World Health Organization declared COVID-19 a global pandemic [2]. As of August 31, 2021, there have been over 200 million confirmed cases of COVID-19 worldwide with over 4.5 million deaths [3].

The spike (S) protein of the SARS-CoV-2 virus is pivotal for its ability to bind and enter host cells [4]. The S protein has two subunits, namely S1 and S2, with S1 allowing for binding to host cells, while S2 carries out the process of fusion between the membranes of the virus and host cell [4]. Angiotensin-converting enzyme (ACE)-2 is the receptor to which the S protein binds [5]. Once binding has occurred, the SARS-CoV-2 virus is able to fuse its membrane with the host cell, allowing it to enter the host cell [6]. The fusion of membranes is mediated by type 2 transmembrane serine protease (TMPRSS2), a cell surface protein which cleaves ACE-2 [7]. Entry into host cells is followed by viral replication and an immune response, causing tissue damage and the clinical manifestations of COVID-19 [4].

COVID-19 typically manifests as pneumonia resulting in symptoms of cough, dyspnea and fever [8]. However, it has since been realized that COVID-19 can cause cardiovascular complications, among these is myocarditis. The disease course of COVID-19 myocarditis can range from mild to severe. If not treated, the myocarditis may progress to life-threatening heart failure and arrythmias; therefore, it is imperative for clinicians to recognize possible cases of COVID-19 myocarditis and treat them accordingly [9,10,11]. Moreover, it may lead to an increase in ward admissions in a time where hospitals can already be overwhelmed. This literature review aims to discuss the pathophysiology and incidence of COVID-19 myocarditis, along with its presentation, diagnosis and treatment.

Pathophysiology of viral myocarditis

Myocarditis is described as inflammation of the heart muscle, leading to damage in the absence of ischemia [12, 13]. Viruses have been suggested to be a significant etiology for myocarditis with a wide variety of causative agents including, but not limited to, adenovirus, parvovirus B19, Epstein Barr virus and cytomegalovirus [13,14,15,16]. Now, recent evidence suggests the SARS-CoV-2 virus may also be a significant infectious agent for myocarditis. The proposed pathophysiology of viral myocarditis is a combination of direct cell injury and immune-mediated cell death [12]. Early in the development of viral myocarditis high rates of viral replication leads to direct cardiomyocyte injury [17]. The damaged cells, and proteins released from them (such as cardiac myosin), activate toll-like receptors and inflammasomes, leading to the release of pro-inflammatory cytokines [18, 19]. As time progresses, these pro-inflammatory cytokines recruit immune cells, including natural killer cells, macrophages and T-lymphocytes, to the myocardium. These cells are involved in immune-mediated myocyte injury [17]. Moreover, interleukin (IL)-1β and IL-17 cause cardiac remodeling and fibrosis, which eventually leads to dilated cardiomyopathy and heart failure [20, 21]. Myocardial fibrosis leads to a disruption in the conduction system, leading to an increased risk of developing arrythmias [22].

Proposed mechanisms for COVID-19 myocarditis

As mentioned previously, the SARS-CoV-2 virus enters human cells by binding to the ACE2 protein. While the ACE2 protein is expressed on epithelial cells (type II alveolar cells) of the respiratory tract, leading to the respiratory manifestations of COVID-19, these proteins can also be found on cardiomyocytes [23,24,25]. A case study, using endomyocardial biopsy (EMB), revealed the presence of SARS-CoV-2 viral particles in the myocardium of a patient with COVID-19 [26]. Furthermore, autopsies of 20 human heart samples of patients infected with SARS-CoV, a virus related to SARS-CoV2, demonstrated seven hearts contained viral particles, alongside macrophage infiltration [27]. Therefore, it is very possible that the SARS-CoV-2 virus can also infect cardiomyocytes leading to viral myocarditis [28]. An alternative way SARS-CoV-2 can cause myocardial damage is via the infection of endothelial cells in the heart [29]. This theory is supported by the discovery of SARS-CoV-2 in endothelial cells of numerous organs, including the heart, under histology [30, 31].

Some authors have found an increased number of diffusely distributed CD68 + cells in hearts of patients with COVID-19, compared to those with typical myocarditis and control groups [32]. Fox et al. hypothesized the difference in immune cells on histology suggest COVID-19 myocarditis is a distinct inflammatory process separate from typical viral myocarditis [32]. Two theories describing the inflammatory process were proposed. First, SARS-CoV-2 can infect endothelial cells within coronary vessels, leading to the migration of macrophages to these areas, causing the activation of complement and apoptosis [32]. Second, the inflammation can lead to thrombus formation in the coronary vessels leading to ischemic myocardial injury [32].

Systemic inflammation may also play a role in the development of COVID-19 myocarditis. IL-6 is a cytokine implicated in the pathophysiology of myocarditis, recruiting inflammatory cells to the myocardium [33]. IL-6 is also a primary mediator of the cytokine storm, a life-threatening condition seen in some patients who have developed COVID-19, which is characterized by extreme increases in pro-inflammatory cytokines and an uncontrolled immune response [33, 34]. This systemic inflammation can further increase the risk of thrombus formation within coronary vessels due to activation of platelets and high levels of clotting factors (including factor V and VIII) [29, 35]. It is also possible that the cytokine storm may lead to exacerbation of established myocarditis and further myocardial injury [28]. Furthermore, myocardial injury may be exacerbated by hypoxia of the myocardium due to increased oxygen demands in the setting of infection, which cannot be met due to the presence of pneumonia of acute respiratory distress syndrome [36]. The possible pathophysiology of COVID-19 myocarditis is outlined in Fig. 1.

Fig. 1
figure 1

Pathophysiology of COVID-19-induced myocarditis. SARS-CoV-2 uses the Spike protein to bind to and enter a variety of cells including type II alveolar cells, cardiomyocytes and endothelial cells. Myocardial inflammation results from the combination of hypoxemia, thrombus-induced ischemia and the migration of proinflammatory cytokines and cells to the area. ACE2= angiotensin-converting enzyme 2; ARDS= acute respiratory distress syndrome; IL-6= interleukin 6; SARS-CoV-2= severe acute respiratory syndrome coronavirus 2; WBC= white blood cell

Full size image

Risk of developing COVID-19 myocarditis

Unfortunately, the incidence of COVID-19-induced myocarditis is unclear. A study revealed that approximately 28% of patients with COVID-19 exhibited myocardial injury, diagnosed by the presence of raised troponin T [37]. A meta-analysis found 8% of patients with COVID-19 developed myocardial injury, with a 13-fold increase in prevalence among patients in intensive care [38]. Halushka et al. found 7.2% of 277 postmortem cases displaying evidence of myocarditis, with only less than 2% of cases demonstrating clinically significant myocarditis [39]. This study reveals that the true incidence of COVID-19 myocarditis may be underestimated, as some patients may be asymptomatic or have minor symptoms. Puntmann et al. studied 100 patients who had recently recovered from severe COVID-19 and found 78% exhibited cardiac involvement on cardiac magnetic resonance imaging (cMRI), with 60% found to have ongoing inflammation [40]. Myocarditis is a significant complication of COVID-19; however, the exact mortality due to these complications remains unclear. Published evidence does show that the myocardial involvement increases mortality in patients hospitalized with COVID-19 [41]. Qiurong et al. demonstrated that among 68 deaths of patients with COVID-19, 7% were attributable to fulminant myocarditis leading to circulatory failure, while 33% died of a combination of respiratory and cardiac failure [42]. The diagnoses of fulminant myocarditis were made based on the evaluation of clinical data available to the authors. There was no mention of analysis of immunohistology which would be the most reliable way of diagnosing myocarditis. This may affect reliability of these results due to an increased risk of misdiagnoses. Myocarditis can worsen prognosis for patients who have developed COVID-19 infection, while patients who develop COVID-19 myocarditis may suffer from long-term cardiovascular complications, which will need to be studied over time.

A systematic review and case series demonstrated that patients with cardiovascular comorbidities were more at risk at developing COVID-19 myocarditis [43, 44]. The exact mechanism as to why this occurs is not completely clear. Guo et al. [45] hypothesized that the virus could travel into the pulmonary circulation after infecting pneumocytes via ACE2 expressing endothelial cells. Furthermore, it has been demonstrated that failing hearts show greater expression of ACE2 proteins than normal [45,46,47]. The higher concentrations of ACE2 in these hearts may allow for easier uptake of the SARS-CoV-2 virus [46]. As the heart is the first organ encountered by pulmonary outflow, the SARS-CoV-2 virus is likely to encounter ACE2 expressing cardiomyocytes in patients with cardiovascular disease [45]. SARS-CoV-2 binds to ACE2 to enter cells meaning these patients may be at a higher risk of developing COVID-19-induced myocarditis [28]. Black, Asian and minority ethnic (BAME) groups may be more seriously affected by COVID-19-induced myocarditis, due to a greater prevalence of cardiovascular disease among these groups [48,49,50,51,52]. However, other evidence suggests that those of African descent express lower levels of ACE2, particularly those of whom with pre-hypertension [52]. The evidence is contradictory and so the association between race and the risk of developing COVID-19 myocarditis requires more research.

An important group to be vigilant of are those who compete in competitive sports as myocarditis is associated with sudden cardiac death in athletes [53]. Daniels et al. tested 1597 athletes for the presence of COVID-19-induced myocarditis. Of these athletes, 37 (2.3%) were diagnosed with COVID-19 myocarditis, 28 of whom were classified as having possible myocarditis [54]. Daniels et al. noted that if cardiac testing were only done on those patients with cardiac symptoms, only five cases of COVID-19 myocarditis would have been recorded [54]. Again, this highlights the possibility that the cardiac involvement of COVID-19 is underestimated due to asymptomatic patients. In another study of 26 competitive athletes who underwent cMRI, 15% were found to have myocarditis, while 31% showed evidence of the previous myocardial damage [55]. Athletes who have recovered from COVID-19 and are returning to sports should receive cardiac testing, including cMRI, to screen for any active myocarditis or the previous cardiac injury.

Overall, the exact incidence of COVID-19 myocarditis is still unclear; however, the current literature suggests that those who suffer from severe infection are at an increased risk of developing myocarditis than those who develop a mild infection.

Association between COVID-19 mRNA vaccine and myocarditis

The administration of a COVID-19 mRNA vaccine (both Pfizer and Moderna) may be associated with a development of myocarditis. Recent evidence suggest that myocarditis rates are around 12.6 cases per million administrations of the second dose of mRNA vaccines among people aged 12–39, with a predominance of young males [56]. Patients tend to present with chest pain and abnormal ECG findings which occur two to three days after the second dose of the vaccine [56]. Patients usually have their symptoms resolved [56]. Diaz et al. discovered an increase mean number of monthly cases of myocarditis/myopericarditis of 10.4 (p < 0.001) since the vaccine started to be rolled out in the USA [57]. Furthermore, multiple case series following patients who develop acute myocarditis following COVID-19 mRNA vaccination have been published [58,59,60,61]. All vaccinated patients studied were confirmed to not have COVID-19 at presentation. Mouch et al. [58] followed five patients presenting after the second dose and one patient presenting after the first dose. Kim et al. [59] followed four patients, all of whom had both doses of the mRNA COVID-19 vaccine. Shaw et al. [60] followed four patients of which two received both doses and two received one dose of the vaccine. Both the patients presenting after the first dose had previous SARS-CoV-2 infection. All patients in these studies underwent diagnostic cMRI. Finally, Montgomery et al. [61] followed 23 male patients, 20 of which presenting following the second dose, while three presented after the first dose (all of whom had previous SARS-CoV-2 infection). However, in this study, only eight patients underwent diagnostic cMRI, affecting the reliability of the results as most diagnoses would have been made by clinical judgment. Overall, these four studies followed 37 patients: 31 presenting after the second dose and 6 presenting after the first dose of the mRNA vaccine with previous COVID-19 infection. This highlights the important point that vaccine-induced myocarditis tends to occur after sensitization to SARS-CoV-2.

A case series following 15 children (12–18 years old) who were hospitalized due to symptoms of myocarditis (such as chest pain and fever) found 13 of these patients had cMRI changes consistent with myocardial inflammation [62]. All but one of these patients presented after the second dose of the vaccine. This study reveals that children may also be at risk of developing myocarditis from administration of mRNA vaccines. Current evidence demonstrates that children with COVID-19 have low mortality and intensive care admission rate [63]. Therefore, recommendations for giving mRNA vaccines to children (under 18 s) should consider the risk of developing myocarditis compared to the risk of severe COVID-19 infection in this age group.

There is evidence that the COVID-19 mRNA vaccine can cause myocarditis, particularly in cases of the previous exposure. With most patients presenting after both doses of the vaccine, or after the first dose with prior SARS-CoV-2 infection, there may be a possibility of a hypersensitivity reaction occurring after the previous exposure [61, 64]. This reaction may be a delayed-type hypersensitivity reaction due to the two- to three-day period between vaccine administration and onset of symptoms seen in most patients [56, 64]. The first vaccine dose could act to sensitize the immune system, while the second dose causes the activation of the effector phase of the immune system [64]. Activated immune cells may migrate to the myocardium leading to release of cytokines into the myocardium. This process can stimulate further immune cells to enter the myocardium, leading to inflammation and the patient may present with myocarditis.

Presentation of COVID-19 myocarditis

Classic presentation of myocarditis is analogous to heart failure, with symptoms of dyspnea, orthopnea and chest pain maybe present [65]. However, clinical presentations of patients with COVID-19 myocarditis can vary from patient to patient. Some patients have relatively mild presentations such as cough, fever and dyspnea [9, 10, 22, 66, 67]. These symptoms may be due to COVID-19 itself and not the myocarditis. Therefore, some patients may have a silent presentation of COVID-19 myocarditis [22]. Some patients may present with chest pain which may or may not be described as a pressure [68,69,70]. In one report this chest pain was present without fatigue, cough or dyspnea [68]. Some patients may also present with palpitations alongside their other symptoms [67, 71]. After initial presentation, patients may deteriorate to develop signs of heart failure and hemodynamic compromise if treatment is not initiated or is inadequate [9,10,11]. In severe cases, patients may initially present with new-onset heart failure in the absence of a history of cardiovascular disease [71]. This is a presentation of fulminant myocarditis, a condition characterized by sudden and severe cardiac inflammation, which may lead to arrythmias, severe heart failure or death [72, 73]. Physicians should be vigilant with patients who present with hypotension, ECG changes (e.g., ventricular tachycardia, bradyarrythmias, ST depression) or clinical signs of heart failure such as peripheral edema [73].

Diagnosing COVID-19 myocarditis

C-reactive protein (CRP), lactate dehydrogenase (LDH) and white cell count (WCC) have been shown to be raised in patients with COVID-19 myocarditis [68,69,70]. These blood tests are markers of infection and, thus, are non-specific to myocarditis. Raised cardiac enzymes (e.g., troponin) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) have also been noted in COVID-19 myocarditis [44, 70]. Therefore, it is a good idea to take baseline levels of troponin I/T and NT-pro-BNP on admission of a patient with COVID-19 allowing a trend of these tests to be established throughout the patients stay [28]. However, some patients with COVID-19 myocarditis may not have a raised troponin, meaning a normal troponin does not rule out myocarditis [22, 74]. In fact, the sensitivity for elevated troponin I levels in myocarditis is 34% [75]. Electrocardiogram (ECG) changes can also be seen with patients who develop myocarditis. Most changes are non-specific and can include sinus tachycardia (the most common change), ST segment elevation/depression, T wave inversions, tachy/bradyarrhythmia and QT prolongation [44, 70]. Therefore, ECG changes are not diagnostic of myocarditis, but they may be helpful as a tool to assess for possible myocardial damage or the presence of arrythmias, indicating severity of disease. Echocardiography may also be used; however, it also shows non-specific changes in myocarditis, including reduced ejection fraction, pericardial effusion and hypokinesis throughout the heart wall [74, 76]. Echocardiography can be useful to rule out other causes of heart failure, such as valvular or congenital causes [74].

cMRI has a high sensitivity for diagnosing myocarditis and is therefore the best noninvasive test [77]. The Lake Louis criteria should be used when interpreting cMRI images [78]. This criterion uses a combination of T2-weighted images, early gadolinium enhancement and late gadolinium enhancement to detect myocardial edema, hyperemia and myocardial necrosis and fibrosis, respectively [78,79,80]. cMRI has shortcomings as it is not possible to distinguish whether the inflammation is caused from an autoimmune response to the virus or from viral infection of the myocardium [78]. Furthermore, when used in patients presenting with severe myocarditis causing cardiogenic shock or hemodynamic instability application of cMRI can be limited as these patients may be mechanically ventilated or have tachyarrhythmias [77, 81]. In these situations, it may be preferred to use EMB which is considered the gold standard test to confirm the presence of myocarditis as it can determine the nature of inflammation [77]. For example, samples from the biopsy can be sent for immunohistology and genomic analysis, which can confirm the diagnosis of COVID-19-induced myocarditis through the presence of SARS-CoV-2 RNA [82]. EMB samples were previously interpreted using the Dallas criteria which described myocarditis as myocyte necrosis or damage associated with inflammatory infiltrates [83]. The reliability of the Dallas criteria is questionable as it has been shown to not apply to 50% of virus positive cases [29]. EMB has further drawbacks including risk of infection and sampling errors due to the patchy inflammation seen in myocarditis [74]. An immunohistochemistry criteria has been added to the Dallas criteria to make it more reliable [29]. This criterion defines myocarditis as the presence of leukocytes ≥ 14/mm2 with monocytes ≤ 4/mm2 and CD3 + cells ≥ 7/mm2 alongside evidence of non-ischemic necrosis under histology [29]. Using this criteria may increase the sensitivity of cMRI in diagnosing COVID-19 myocarditis.

During the COVID-19 pandemic, the availability of scans, such as cMRI, has been greatly reduced, while due to the risk of infection EMB is likely avoided on patients with COVID-19 [70, 84]. Therefore, physicians may need to use a combination of blood tests, ECGs, echocardiograms and a high clinical suspicion for myocarditis to reach a diagnosis if hospitals are under pressure from COVID-19.

Managing COVID-19 myocarditis

Treating myocarditis involves the management of both the myocardial inflammation and the complications that may arise from it. Intravenous immunoglobulins (IVIG) have been studied for their efficacy in treating viral myocarditis. IgG, IgA and IgM immunoglobulins have anti-inflammatory effects, while neutralizing and facilitating the clearance of pathogens from the myocardium [85]. Maisch et al. demonstrated that immunoglobulin therapy for biopsy proven cytomegalovirus myocarditis showed favorable outcomes with a reduction in inflammatory and viral levels [86]. However, in cases of suspected myocarditis with no biopsy proof of viral infection, use of immunoglobin therapy showed inconsistent results [86]. Hu et al. used a combination of glucocorticoid and immunoglobulin treatment to successfully treat COVID-19 myocarditis [87]. A meta-analysis revealed that the use of IVIG to treat acute myocarditis significantly reduced mortality, while improving left ventricular ejection fraction [88]. Moreover, the effect of IVIG was even more noticeable in patients with fulminant myocarditis where it showed to significantly increase survival rates of this life-threatening condition [88]. The evidence for use of corticosteroids to treat COVID-19 myocarditis is not as clear. The use of the corticosteroid, prednisolone, may be effective in treating viral myocarditis in the absence of viral replication [89]. It is thought that the use of immunocompromising medication, such as corticosteroids, may worsen acute myocarditis where viral replication is present [90]. A systematic review by Sawalha et al. revealed the use of corticosteroids showed improved outcomes among patients with COVID-19 myocarditis [76]. This comes with the caveat that the review consisted of 14 case reports, and therefore, the evidence lacks in reliability. On the other hand, other studies show the use of corticosteroid therapy does not reduce mortality in patients with viral myocarditis [91]. Tocilizumab, which is an anti-IL-6 receptor monoclonal antibody, was trialed with the combination of the anti-viral, favipiravir, to treat COVID-19 patients who had developed cytokine storm [92]. The trial found that the combination of Tocilizumab and favipiravir significantly reduced inflammation caused by cytokine storm [92]. As COVID-19 myocarditis may be exacerbated by cytokine storm, the use of this combination therapy may provide positive outcomes [28]. Although there is evidence to show the efficacy of IVIG in the treatment of viral myocarditis, more research is needed to assess the effects on COVID-19 myocarditis specifically. Dexamethasone, a corticosteroid, is currently used in the management of COVID-19. Therefore, research into assessing the efficacy of Dexamethasone may reveal if current treatment is sufficient or if patients who develop COVID-19 myocarditis require extra anti-viral/anti-inflammatory treatment.

Patients who present with cardiogenic shock due to fulminant myocarditis need further management. For patients with cardiogenic shock, the use of inotropic agents, such as dobutamine, and mechanical support, including intra-aortic balloon pumps or Impella systems, can be used to maintain blood pressure [74, 77]. The presence of tachyarrhythmias can be treated with intravenous amiodarone hydrochloride, or, if the patient is unstable or unresponsive to pharmacological intervention, direct current cardioversion or pacing may be used [93]. Bradyarrhythmias which may occur can be treated by intravenous atropine or, if required, transcutaneous pacing can be commenced [93].

Conclusions

COVID-19 myocarditis is a significant complication of SARS-CoV-2 infection which can worsen the prognosis for patients. While some cases may be insignificant or asymptomatic, it is likely clinicians will come across cases which are more severe and require prompt treatment. Therefore, it is imperative to recognize how to diagnose and treat this condition. If possible, it is a good idea to carry out serial troponins and ECGs to monitor for any development of myocarditis or other myocardial injury. As the symptoms for myocarditis can be non-specific and can overlap with the respiratory symptoms of COVID-19, it may be hard to diagnose this condition. It is important to have a low threshold to work up a patient, as initial tests are relatively inexpensive. Further testing should be used for patients with evidence of myocardial injury on initial work up, these include echocardiography, cMRIs and EMB. Clinicians should be vigilant for any signs of heart failure or arrhythmias, as these could be the life-threatening signs of fulminant myocarditis. While no definitive treatment for COVID-19 myocarditis has been published, the combination of IVIG and corticosteroids shows promise to reduce mortality, particularly in the case of fulminant myocarditis.

Availability of data and materials

Not applicable.

Abbreviations

COVID-19:

Coronavirus disease 2019

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

S:

Spike

ACE:

Angiotensin-converting enzyme

TMPRSS2:

Type 2 transmembrane serine protease

IL:

Interleukin

EMB:

Endomyocardial biopsy

cMRI:

Cardiac magnetic resonance imagining

BAME:

Black, Asian and minority ethnic

CRP:

C-reactive protein

LDH:

Lactate dehydrogenase

WCC:

White cell count

NT-pro-BNP:

N-terminal pro-B-type natriuretic peptide

ECG:

Electrocardiogram

IVIG:

Intravenous immunoglobulins

References

  1. Dong E, Du H, Gardner L (2020) An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 20(5):533–534. https://doi.org/10.1016/S1473-3099(20)30120-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cascella M, Rajnik M, Aleem A, Dulebohn SC, di Napoli R (2021)Features, Evaluation, and Treatment of Coronavirus (COVID-19)

  3. WHO Coronavirus (COVID-19) Dashboard. Covid19.who.int. Accessed September 13, 2021. https://covid19.who.int/

  4. Parasher A (2021) COVID-19: current understanding of its pathophysiology, clinical presentation and treatment. Postgrad Med J 97(1147):312. https://doi.org/10.1136/postgradmedj-2020-138577

    Article  PubMed  Google Scholar 

  5. Li W, Moore MJ, Vasilieva N et al (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426(6965):450–454. https://doi.org/10.1038/nature02145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Belouzard S, Millet JK, Licitra BN, Whittaker GR (2012) Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4(6):1011–1033. https://doi.org/10.3390/v4061011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC (2020) Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 324(8):782–793. https://doi.org/10.1001/jama.2020.12839

    Article  CAS  PubMed  Google Scholar 

  8. Mele D, Flamigni F, Rapezzi C, Ferrari R (2021) Myocarditis in COVID-19 patients: current problems. Intern Emerg Med 16(5):1123–1129. https://doi.org/10.1007/s11739-021-02635-w

    Article  PubMed  Google Scholar 

  9. Marcinkiewicz K, Petryka-Mazurkiewicz J, Nowicki M et al (2021) Acute heart failure in the course of fulminant myocarditis requiring mechanical circulatory support in a healthy young patient after coronavirus disease 2019. Kardiologia Polska (Polish Heart J) 79(5):583–584. https://doi.org/10.33963/KP.15888

    Article  Google Scholar 

  10. Inciardi RM, Lupi L, Zaccone G et al (2020) Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol 5(7):819–824. https://doi.org/10.1001/jamacardio.2020.1096

    Article  PubMed  Google Scholar 

  11. Pascariello G, Cimino G, Calvi E et al (2020) Cardiogenic shock due to COVID-19-related myocarditis in a 19-year-old autistic patient. J Med Cases 11(7):207–210. https://doi.org/10.14740/jmc3517

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cooper LT Jr (2009) Myocarditis. N Engl J Med 360(15):1526–1538. https://doi.org/10.1056/NEJMra0800028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Baboonian C, Treasure T (1997) Meta-analysis of the association of enteroviruses with human heart disease. Heart (British Cardiac Society) 78(6):539–543. https://doi.org/10.1136/hrt.78.6.539

    Article  CAS  Google Scholar 

  14. Caforio ALP, Calabrese F, Angelini A et al (2007) A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 28(11):1326–1333. https://doi.org/10.1093/eurheartj/ehm076

    Article  PubMed  Google Scholar 

  15. Agrawal AS, Garron T, Tao X et al (2015) Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 89(7):3659–3670. https://doi.org/10.1128/JVI.03427-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Esfandiarei M, McManus BM (2008) Molecular biology and pathogenesis of viral myocarditis. Annu Rev Pathol 3(1):127–155. https://doi.org/10.1146/annurev.pathmechdis.3.121806.151534

    Article  CAS  PubMed  Google Scholar 

  17. Seko Y, Takahashi N, Yagita H, Okumura K, Yazaki Y (1997) Expression of cytokine mRNAs in murine hearts with acute myocarditis caused by coxsackievirus B3. J Pathol 183(1):105–108. https://doi.org/10.1002/(SICI)1096-9896(199709)183:1%3c105::AID-PATH1094%3e3.0.CO;2-E

    Article  CAS  PubMed  Google Scholar 

  18. Cihakova D, Sharma R, Fairweather D, Afanasyeva M, Rose N (2004) Animal models for autoimmune myocarditis and autoimmune thyroiditis. Methods Mol Med 102:175–193. https://doi.org/10.1385/1-59259-805-6:175

    Article  CAS  PubMed  Google Scholar 

  19. Zhang P, Cox CJ, Alvarez KM, Cunningham MW (2009) Cutting edge: cardiac myosin activates innate immune responses through TLRs. J Immunol (Baltimore, Md) 183(1):27–31. https://doi.org/10.4049/jimmunol.0800861

    Article  CAS  Google Scholar 

  20. Blyszczuk P, Kania G, Dieterle T et al (2009) Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy. Circ Res 105(9):912–920. https://doi.org/10.1161/CIRCRESAHA.109.199802

    Article  CAS  PubMed  Google Scholar 

  21. Baldeviano GC, Barin JG, Talor Mv et al (2010) Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. Circul Res 106(10):1646–1655. https://doi.org/10.1161/CIRCRESAHA.109.213157

    Article  CAS  Google Scholar 

  22. Oleszak F, Maryniak A, Botti E et al (2020) Myocarditis associated With COVID-19. Am J Med Case Rep 8(12):498–502. https://doi.org/10.12691/ajmcr-8-12-19

    Article  PubMed  PubMed Central  Google Scholar 

  23. Qian Z, Travanty EA, Oko L et al (2013) Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol 48(6):742–748. https://doi.org/10.1165/rcmb.2012-0339OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goulter AB, Goddard MJ, Allen JC, Clark KL (2004) ACE2 gene expression is up-regulated in the human failing heart. BMC Med 2:19. https://doi.org/10.1186/1741-7015-2-19

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sharma YP, Agstam S, Yadav A, Gupta A, Gupta A (2021) Cardiovascular manifestations of COVID-19: an evidence-based narrative review. Indian J Med Res 153(1 & 2):7–16. https://doi.org/10.4103/ijmr.IJMR_2450_20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tavazzi G, Pellegrini C, Maurelli M et al (2020) Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 22(5):911–915. https://doi.org/10.1002/ejhf.1828

    Article  CAS  PubMed  Google Scholar 

  27. Oudit GY, Kassiri Z, Jiang C et al (2009) SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest 39(7):618–625. https://doi.org/10.1111/j.1365-2362.2009.02153.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Siripanthong B, Nazarian S, Muser D et al (2020) Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm 17(9):1463–1471. https://doi.org/10.1016/j.hrthm.2020.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kawakami R, Sakamoto A, Kawai K et al (2021) Pathological evidence for SARS-CoV-2 as a cause of myocarditis: JACC review topic of the week. J Am Coll Cardiol 77(3):314–325. https://doi.org/10.1016/j.jacc.2020.11.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fox SE, Li G, Akmatbekov A et al (2020) Unexpected features of cardiac pathology in COVID-19 infection. Circulation 142(11):1123–1125. https://doi.org/10.1161/CIRCULATIONAHA.120.049465

    Article  CAS  PubMed  Google Scholar 

  31. Varga Z, Flammer AJ, Steiger P et al (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet (London, England) 395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5

    Article  CAS  Google Scholar 

  32. Fox SE, Falgout L, vandar Heide RS (2021) COVID-19 myocarditis: quantitative analysis of the inflammatory infiltrate and a proposed mechanism. Cardiovasc Pathol 54:107361. https://doi.org/10.1016/j.carpath.2021.107361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lee DW, Gardner R, Porter DL et al (2014) Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124(2):188–195. https://doi.org/10.1182/blood-2014-05-552729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M (2020) The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 53:25–32. https://doi.org/10.1016/j.cytogfr.2020.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Talasaz AH, Sadeghipour P, Kakavand H et al (2021) Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC state-of-the-art review. J Am Coll Cardiol 77(15):1903–1921. https://doi.org/10.1016/j.jacc.2021.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Guzik TJ, Mohiddin SA, Dimarco A et al (2020) COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 116(10):1666–1687. https://doi.org/10.1093/cvr/cvaa106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Guo T, Fan Y, Chen M et al (2020) Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 5(7):811–818. https://doi.org/10.1001/jamacardio.2020.1017

    Article  PubMed  Google Scholar 

  38. Li B, Yang J, Zhao F et al (2020) Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol 109(5):531–538. https://doi.org/10.1007/s00392-020-01626-9

    Article  CAS  PubMed  Google Scholar 

  39. Halushka MK, vandar Heide RS (2021) Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations. Cardiovasc Pathol 50:107300. https://doi.org/10.1016/j.carpath.2020.107300

    Article  CAS  PubMed  Google Scholar 

  40. Puntmann VO, Carerj ML, Wieters I et al (2020) Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 5(11):1265–1273. https://doi.org/10.1001/jamacardio.2020.3557

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shi S, Qin M, Shen B et al (2020) Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 5(7):802–810. https://doi.org/10.1001/jamacardio.2020.0950

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ruan Q, Yang K, Wang W, Jiang L, Song J (2020) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 46(5):846–848. https://doi.org/10.1007/s00134-020-05991-x

    Article  CAS  PubMed  Google Scholar 

  43. Laganà N, Cei M, Evangelista I et al (2021) Suspected myocarditis in patients with COVID-19: a multicenter case series. Medicine 100(8):e24552–e24552. https://doi.org/10.1097/MD.0000000000024552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Omidi F, Hajikhani B, Kazemi SN et al (2021) COVID-19 and cardiomyopathy: a systematic review. Front Cardiovasc Med 8:695206. https://doi.org/10.3389/fcvm.2021.695206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Guo J, Wei X, Li Q et al (2020) Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury. J Cell Physiol 235(12):9884–9894. https://doi.org/10.1002/jcp.29802

    Article  CAS  PubMed  Google Scholar 

  46. Ma M, Xu Y, Su Y et al (2021) Single-cell transcriptome analysis decipher new potential regulation mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2. Front Cardiovasc Med. https://doi.org/10.3389/fcvm.2021.628885

    Article  PubMed  PubMed Central  Google Scholar 

  47. Chen L, Li X, Chen M, Feng Y, Xiong C (2020) The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 116(6):1097–1100. https://doi.org/10.1093/cvr/cvaa078

    Article  CAS  PubMed  Google Scholar 

  48. Pan D, Sze S, Minhas JS et al (2020) The impact of ethnicity on clinical outcomes in COVID-19: a systematic review. EClinicalMedicine 23:100404. https://doi.org/10.1016/j.eclinm.2020.100404

    Article  PubMed  PubMed Central  Google Scholar 

  49. Myers VD, Gerhard GS, McNamara DM et al (2018) Association of variants in BAG3 with cardiomyopathy outcomes in African American Individuals. JAMA Cardiol 3(10):929–938. https://doi.org/10.1001/jamacardio.2018.2541

    Article  PubMed  PubMed Central  Google Scholar 

  50. Leigh JA, Alvarez M, Rodriguez CJ (2016) Ethnic minorities and coronary heart disease: an update and future directions. Curr Atheroscler Rep 18(2):9. https://doi.org/10.1007/s11883-016-0559-4

    Article  PubMed  PubMed Central  Google Scholar 

  51. Abuelgasim E, Saw LJ, Shirke M, Zeinah M, Harky A (2020) COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities. Curr Probl Cardiol 45(8):100621. https://doi.org/10.1016/j.cpcardiol.2020.100621

    Article  PubMed  PubMed Central  Google Scholar 

  52. Vinciguerra M, Greco E (2020) Sars-CoV-2 and black population: ACE2 as shield or blade? Infection Genetics Evol J Mol Epidemiol Evolut Genetics Infect Diseases 84:104361. https://doi.org/10.1016/j.meegid.2020.104361

    Article  CAS  Google Scholar 

  53. Maron BJ, Udelson JE, Bonow RO et al (2015) Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. Circulation. https://doi.org/10.1161/CIR.0000000000000239

    Article  PubMed  PubMed Central  Google Scholar 

  54. Daniels CJ, Rajpal S, Greenshields JT et al (2021) Prevalence of clinical and subclinical myocarditis in competitive athletes with recent SARS-CoV-2 infection. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2021.2065

    Article  PubMed  PubMed Central  Google Scholar 

  55. Rajpal S, Tong MS, Borchers J et al (2021) Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol 6(1):116–118. https://doi.org/10.1001/jamacardio.2020.4916

    Article  PubMed  Google Scholar 

  56. Bozkurt B, Kamat I, Hotez PJ (2021) Myocarditis with COVID-19 mRNA vaccines. Circulation 144(6):471–484. https://doi.org/10.1161/CIRCULATIONAHA.121.056135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson Iv, Robicsek A (2021) Myocarditis and pericarditis after vaccination for COVID19. JAMA. https://doi.org/10.1001/jama.2021.13443

    Article  PubMed  PubMed Central  Google Scholar 

  58. Abu Mouch S, Roguin A, Hellou E et al (2021) Myocarditis following COVID-19 mRNA vaccination. Vaccine 39(29):3790–3793. https://doi.org/10.1016/j.vaccine.2021.05.087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kim HW, Jenista ER, Wendell DC et al (2021) Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2021.2828

    Article  PubMed  PubMed Central  Google Scholar 

  60. Shaw KE, Cavalcante JL, Han BK, Gössl M (2021) Possible association between COVID-19 vaccine and myocarditis: clinical and CMR findings. JACC Cardiovasc Imaging 14(9):1856–1861. https://doi.org/10.1016/j.jcmg.2021.06.002

    Article  PubMed  PubMed Central  Google Scholar 

  61. Montgomery J, Ryan M, Engler R et al (2021) Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2021.2833

    Article  PubMed  Google Scholar 

  62. Dionne A, Sperotto F, Chamberlain S et al (2021) Association of myocarditis with BNT162b2 messenger RNA COVID-19 vaccine in a case series of children. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2021.3471

    Article  PubMed  Google Scholar 

  63. Bhopal SS, Bagaria J, Olabi B, Bhopal R (2021) Children and young people remain at low risk of COVID-19 mortality. Lancet Child Adolescent Health 5(5):e12–e13. https://doi.org/10.1016/S2352-4642(21)00066-3

    Article  CAS  PubMed  Google Scholar 

  64. D’Angelo T, Cattafi A, Carerj ML et al (2021) Myocarditis after SARS-CoV-2 vaccination: a vaccine-induced reaction? Can J Cardiol. https://doi.org/10.1016/j.cjca.2021.05.010

    Article  PubMed  Google Scholar 

  65. Al-Akchar M, Kiel J (2021) Acute Myocarditis

  66. Kim IC, Kim JY, Kim HA, Han S (2020) COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J 41(19):1859. https://doi.org/10.1093/eurheartj/ehaa288

    Article  CAS  PubMed  Google Scholar 

  67. Das BB (2021) SARS-CoV-2 myocarditis in a high school athlete after COVID-19 and its implications for clearance for sports. Children (Basel, Switzerland) 8(6):427. https://doi.org/10.3390/children8060427

    Article  Google Scholar 

  68. Fried JA, Ramasubbu K, Bhatt R et al (2020) The variety of cardiovascular presentations of COVID-19. Circulation 141(23):1930–1936. https://doi.org/10.1161/CIRCULATIONAHA.120.047164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Okor I, Sleem A, Zhang A, Kadakia R, Bob-Manuel T, Krim SR (2021) Suspected COVID-19-induced myopericarditis. Ochsner J 21(2):181–186. https://doi.org/10.31486/toj.20.0090

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ho JS, Sia CH, Chan MY, Lin W, Wong RC (2020) Coronavirus-induced myocarditis: a meta-summary of cases. Heart Lung J Crit Care 49(6):681–685. https://doi.org/10.1016/j.hrtlng.2020.08.013

    Article  Google Scholar 

  71. Gaine S, Devitt P, Coughlan JJ, Pearson I (2021) COVID-19-associated myocarditis presenting as new-onset heart failure and atrial fibrillation. BMJ Case Rep 14(7):e244027. https://doi.org/10.1136/bcr-2021-244027

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kociol RD, Cooper LT, Fang JC et al (2020) Recognition and initial management of fulminant myocarditis. Circulation 141(6):e69–e92. https://doi.org/10.1161/CIR.0000000000000745

    Article  PubMed  Google Scholar 

  73. Wang Z, Wang Y, Lin H, Wang S, Cai X, Gao D (2019) Early characteristics of fulminant myocarditis vs non-fulminant myocarditis: a meta-analysis. Medicine 98(8):e14697–e14697. https://doi.org/10.1097/MD.0000000000014697

    Article  PubMed  PubMed Central  Google Scholar 

  74. Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS (2009) Diagnosis and treatment of viral myocarditis. Mayo Clin Proc 84(11):1001–1009. https://doi.org/10.1016/S0025-6196(11)60670-8

    Article  PubMed  PubMed Central  Google Scholar 

  75. Smith SC, Ladenson JH, Mason JW, Jaffe AS (1997) Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation 95(1)

  76. Sawalha K, Abozenah M, Kadado AJ et al (2021) Systematic review of COVID-19 related myocarditis: insights on management and outcome. Cardiovasc Revascular Med Include Mol Intervent 23:107–113. https://doi.org/10.1016/j.carrev.2020.08.028

    Article  Google Scholar 

  77. Tschöpe C, Cooper LT, Torre-Amione G, van Linthout S (2019) Management of myocarditis-related cardiomyopathy in adults. Circ Res 124(11):1568–1583. https://doi.org/10.1161/CIRCRESAHA.118.313578

    Article  CAS  PubMed  Google Scholar 

  78. Ferreira VM, Schulz-Menger J, Holmvang G et al (2018) Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations. J Am Coll Cardiol 72(24):3158–3176. https://doi.org/10.1016/j.jacc.2018.09.072

    Article  PubMed  Google Scholar 

  79. Friedrich MG, Sechtem U, Schulz-Menger J et al (2009) Cardiovascular magnetic resonance in myocarditis: a JACC White Paper. J Am Coll Cardiol 53(17):1475–1487. https://doi.org/10.1016/j.jacc.2009.02.007

    Article  PubMed  PubMed Central  Google Scholar 

  80. Ho JS, Sia CH, Chan MY, Lin W, Wong RC (2020) Coronavirus-induced myocarditis: a meta-summary of cases. Heart Lung J Critical Care 49(6):681–685. https://doi.org/10.1016/j.hrtlng.2020.08.013

    Article  Google Scholar 

  81. Ferreira MV, Jeanette SM, Godtfred H et al (2018) Cardiovascular magnetic resonance in nonischemic myocardial inflammation. J Am College Cardiol. 72(24):3158–3176. https://doi.org/10.1016/j.jacc.2018.09.072

    Article  Google Scholar 

  82. Leone O, Veinot JP, Angelini A et al (2012) 2011 Consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathol 21(4):245–274. https://doi.org/10.1016/j.carpath.2011.10.001

    Article  PubMed  Google Scholar 

  83. Aretz HT (1987) Myocarditis: the Dallas criteria. Human Pathol. https://doi.org/10.1016/s0046-8177(87)80363-5

    Article  Google Scholar 

  84. Secco GG, Tarantini G, Mazzarotto P et al (2021) Invasive strategy for COVID patients presenting with acute coronary syndrome: the first multicenter Italian experience. Catheter Cardiovasc Interv 97(2):195–198. https://doi.org/10.1002/ccd.28959

    Article  PubMed  Google Scholar 

  85. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320(5874):373–376. https://doi.org/10.1126/science.1154315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Maisch B, Hufnagel G, Kölsch S et al (2004) Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with immunosuppression and i.v. immunoglobulins. Herz 29(6):624–636. https://doi.org/10.1007/s00059-004-2628-7

    Article  PubMed  Google Scholar 

  87. Hu H, Ma F, Wei X, Fang Y (2021) Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. Eur Heart J 42(2):206. https://doi.org/10.1093/eurheartj/ehaa190

    Article  CAS  PubMed  Google Scholar 

  88. Huang X, Sun Y, Su G, Li Y, Shuai X (2019) Intravenous immunoglobulin therapy for acute myocarditis in children and adults. Int Heart J 60(2):359–365. https://doi.org/10.1536/ihj.18-299

    Article  PubMed  Google Scholar 

  89. Tschöpe C, van Linthout SS, Pieske B, Kühl U (2018) Immunosuppression in lymphocytic myocarditis with parvovirus B19 presence. Eur J Heart Failure 20:609

    Article  Google Scholar 

  90. Abdelnabi M, Eshak N, Saleh Y, Almaghraby A (2020) Coronavirus disease 2019 myocarditis: insights into pathophysiology and management. Eur Cardiol Rev. https://doi.org/10.15420/ecr.2020.16

    Article  Google Scholar 

  91. Chen HS, Wang W, Wu SN, Liu JP (2013) Corticosteroids for viral myocarditis. Cochrane Database Syst Rev 2013(10):CD004471–CD004471. https://doi.org/10.1002/14651858.CD004471.pub3

    Article  PubMed Central  Google Scholar 

  92. Zhao H, Zhu Q, Zhang C et al (2021) Tocilizumab combined with favipiravir in the treatment of COVID-19: a multicenter trial in a small sample size. Biomed Pharmacother 133:110825. https://doi.org/10.1016/j.biopha.2020.110825

    Article  CAS  PubMed  Google Scholar 

  93. (2005) Part 7.3: management of symptomatic bradycardia and tachycardia. Circulation 112(24_supplement):IV-67–IV-77. https://doi.org/10.1161/CIRCULATIONAHA.105.166558

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. School of Medicine, The University of Manchester, Stopford Building, 99 Oxford Road, Manchester, M13 9PG, UK

    Mohammed Ali

  2. Burnley General Hospital, Burnley, UK

    Haaris A. Shiwani

  3. School of Medicine, University College Dublin, Dublin, Ireland

    Mohammed Y. Elfaki

  4. Birmingham Midland Eye Centre, Birmingham, UK

    Moaz Hamid

  5. St Vincent’s University Hospital, Dublin, Ireland

    Rebabonye Pharithi & Rene Kamgang

  6. Faculty of Medicine, University of N’Djamena, N’djamena, Chad

    Christian BinounA Egom

  7. Laboratory of Endocrinology and Radioisotopes, Institute of Medical Research and Medicinal Plants Studies (IMPM), Yaoundé, Cameroon

    Jean Louis Essame Oyono & Emmanuel Eroume-A Egom

  8. Institut du Savoir Montfort (ISM), Hôpital Montfort, 713 Montreal Rd, Ottawa, ON, K1K 0T2, Canada

    Emmanuel Eroume-A Egom

Authors
  1. Mohammed Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haaris A. Shiwani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammed Y. Elfaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moaz Hamid
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rebabonye Pharithi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rene Kamgang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christian BinounA Egom
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jean Louis Essame Oyono
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emmanuel Eroume-A Egom
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AM, SH, EM, HM, PR, KR, EC, OJ and EE all made contributions to the literature search and drafting the manuscript. AM produced the figure, revised the manuscript and made final changes. All authors read and approved the manuscript before submission.

Corresponding author

Correspondence to Mohammed Ali.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ali, M., Shiwani, H.A., Elfaki, M.Y. et al. COVID-19 and myocarditis: a review of literature. Egypt Heart J 74, 23 (2022). https://doi.org/10.1186/s43044-022-00260-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43044-022-00260-2

Keywords

  • COVID-19
  • SARS-CoV-2
  • Myocarditis
  • Vaccine
  • Intravenous immunoglobulins