Discussion:
COVID-19 may present with cardiovascular manifestations and complications. Although, currently it has been considered as an established etiology of myocarditis, there is no clear recommendation and consensus regarding the best clinical approach and the management of myocarditis following COVID-19.6-8,10-13
Here, we reported, a case of GCM following COVID-19 infection. Recently, Blagova et al. have reported a cardiomyopathy that was rapidly progressed to a sudden cardiac death following COVID -19 in a patient with a history of chronic adrenal insufficiency and myocardial disease with a final diagnosis GCM.9 As far as we researched, our case seems to be the first case report of GCM following COVID-19 in a patient with a background of autoimmune disorder, without any cardiac problem who was successfully treated with immunosuppressive therapy.
The etiology of GCM is unknown; however, an association with autoimmune diseases has been suggested. Many GCM cases are patients with immunological based diseases, such as thymoma, myasthenia gravis, dermatomyositis, thyroiditis, and pernicious anemia.1,3,4,14-16This association has prompted an autoimmune hypothesis for the etiology of GCM. Our patient had a history of an autoimmune dermatologic and thyroid disease.
It has been suggested that, patients with chronic and long term lichen plan (LP) dermatitis particularly those with erosive LP may have arterial stiffness secondary to autoimmune endothelial dysfunction and should be followed up in terms of cardiovascular disorders. However, the combination of GCM with autoimmune dermatologic including lichen planus has not been described yet.17,18
Another issue which should be considered in patients with LP dermatitis is its differential diagnosis with sarcoidosis. In a case series, Goldberg et al, have suggested that the LP can induce epidermotropic multinucleated giant cell inflammatory response and sarcoidosis with systemic involvement should be considered and worked up in these patients.19
Cardiac sarcoidosis (CS) could be considered as differential diagnosis of our patient. However, although cardiac sarcoidosis and giant cell myocarditis can be pathologically similar and pathological differentiation between the two may be difficult, cardiac sarcoidosis is not known to cause fulminant myocarditis and typically has a chronic course. Although there are a few reports of fulminant cardiac sarcoidosis, the treatment response of our patient could be in favor of GCM than CS.15,20-23
Since the beginning of the COVID-19 disaster, physicians have encountered a variety of clinical manifestations and complications of this disease and it seems that we should expect a stranger behavior of this virus overtime. COVID-19 is associated with a hyperinflammation and activated humoral and cell-mediated immune response in human body, particularly in its severe forms.8,12
Although, the mechanisms of COVID-19-related myocardial injury are not completely understood, the role of severe inflammatory response with significant cytokines release, predominantly interleukin-6 (IL-6), has been recognized. Data from COVID-19 victims show mechanisms such as vasculitis, extended endotheliitis, lymphocyte infiltration, and direct injury of cardiomyocytes by binding spike protein of the SARS-CoV-2 to the membrane protein angiotensin-converting enzyme 2, which may be involved in acute cardiac injury and myocarditis following COVID-19.5-12,24,25
The presence of microvascular dysfunction accompanied with a myocardial inflammatory process may be an explanation for the sub-endocardial ischemic pattern noticed in cardiac magnetic resonance of patients with COVID-19 like what was seen in our patient and the case reported by Blagova et al.9
Although the clinical presentation of COVID-19 was mild, we believe that the autoimmune reactions following COVID-19 in our patient, who had a background of autoimmune abnormality, have caused GCM which was successfully controlled by immunosuppressive therapies. Choosing an optimal evidence‐based immunosuppression regimen was challenging in this setting.
We opted to employ a combined immunosuppressive therapy utilizing IVIG, corticosteroid, tacrolimus and mycophenolate mofetil for our patient based on earlier reports concerning the treatment of GCM and our center’s previous experience with the treatment of GCM and recent COVID-19 infection.1,2,5,13,14,16
However, several questions remained unanswered which will be clarified over time. First, as there are several reports of acute myocarditis following COVID-19 vaccination, which of the COVID-19 vaccines would be safe in patients who had myocarditis following COVID-19 infection, particularly those with inflammatory myocarditis such as GCM.26,27Secondly, the necessity of further systemic work up including FDG-PET or CMR and/or repeated EMBx to exclude CS or for prognostication. Third, what would be the correct surveillance for electrophysiologic complications in this patient? Despite the fact that our patient never developed arrhythmias or atrioventricular block, her LVEF increased to 40% and up to now she remains asymptomatic, we advised her for ICD implantation for the primary prevention.
In conclusion, it seems that the development of myocarditis in COVID 19 would be independent of the severity of the illness. The current report supports the role of autoimmunity and immunosuppressive therapy in COVID-19 myocarditis including the inflammatory ones such as GCM. Further investigations are needed to determine the appropriate diagnostic and prognostic approach in patients with this type of myocarditis and necessity of surveillance regarding the myocardial inflammatory disorders in known cases of autoimmune diseases who have COVID-19 infection without cardiac injury.