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.