COVID | Free Full-Text | Three Years of COVID-19 Pandemic—Is the Heart Skipping a Beat?

Direct viral injury together with a generalised inflammatory response, diffuse vasculitis and/or cardiotoxic anti-viral therapies are considered to induce COVID-19-related myocarditis [28]. However, its pathogenesis remains a subject of debate. Potential mechanisms associated with the onset of myocarditis are separated, as previously mentioned, into two main categories: direct viral action and its indirect effects [19]. Direct viral invasion has been described in isolated cases of fulminant myocarditis associated with COVID-19, where RNA was present at the level of cardiomyocytes [29]. Fulminant myocarditis, which is characterized by a lymphocytic infiltrate on endomyocardial biopsies, remains an infrequent complication of COVID-19 infections [30]. One of the pathophysiological mechanisms linked to the onset of acute myocarditis among patients with COVID-19 is the viral invasion via the spike protein that connects to angiotensin-converting enzyme 2 receptors expressed by various cells including macrophages, thereby promoting inflammation at this level [4,19]. Moreover, in specific clinical situations where an endomyocardial biopsy was performed to confirm the diagnosis of myocarditis, COVID-19 RNA was identified supporting the theory of direct viral invasion [13,30]. The mortality rate among COVID-19 patients is considered to be less than 1%, with myocarditis being a potential cause of a worse outcome [31,32]. However, the prevalence of acute myocarditis is considered to be low, being considered as an uncommon finding among patients with COVID-19 [33]. A recent study described the occurrence of myocarditis in COVID-19 between 2.4 and 4.1 out of 1000 hospitalized patients, which is in contrast with earlier data where the prevalence was up to 60% based mainly on presumed myocarditis diagnosis without actual established diagnosis criteria [34,35]. A multicentric report including 1047 patients described the myocarditis pattern via cardiac magnetic resonance (CMR) in 7.9% of the patients [36]; however, it was limited by the retrospective nature and variability in the CMR protocols used in various centres, along with the absence of previous CMR examinations prior to COVID-19 to exclude pre-existing abnormalities. Nevertheless, the incidence of myocarditis was 42.3% higher in 2020 than it was in 2019, with an increased risk of 0.146% among patients with COVID-19 versus 0.009% among COVID-19-negative patients, respectively. However, it was not possible to determine causality based on the abovementioned data [33]. In the same report, patients with COVID-19 have a 16 times higher risk of developing myocarditis than patients without COVID-19 do [33]. Additionally, several reports evaluated its prevalence among young competitive athletes with a history of COVID-19 due to the high risk of sudden death in this particular population. In one of the largest studies involving 1597 competitive athletes, 37 (2.3%) patients presented clinical and subclinical characteristics suggestive of myocarditis [37]. Other reports consisting of smaller cohorts described a prevalence of myocarditis associated with a COVID-19 infection in up to 15% of them [38,39,40,41]; however, they were limited by differences in the time of examination following the acute episode of COVID-19 or the protocols used for CMR evaluation. In a recent study focusing on myocardial involvement among COVID-19 patients, the authors concluded that excess scarring described during CMR evaluation is predominantly due to myocardial infarction and microinfarction, emphasizing the prothrombotic state of COVID-19 [42]. Additionally, the same report concluded that the prevalence of myocarditis was low, and the pathogenesis of cardiac troponin elevation in this population remains diverse [42]. Nevertheless, COVID-19-associated myocarditis remains a difficult diagnosis to establish in the context of COVID-19 pneumonia due to the similarity of symptoms; one distinguished characteristic would be the early shock state that accompanies the onset of myocarditis in COVID-19 patients [43].