In addition to pulmonary involvement, SARS-CoV-2 infection can impair myocardial function, triggering cases of acute myocarditis. Myocarditis, an inflammatory disease of the myocardium, is one of the manifestations of myocardial injury. Viral infections - such as enteroviroses and adenoviroses - are common causes of this condition, which causes focal or global myocardial inflammation, necrosis, and in some cases ventricular dysfunction.(15) The diagnosis of myocarditis is based on several parameters, since this condition can manifest from a subclinical disease to sudden death. The symptoms of myocarditis usually present as chest pain, palpitations, fatigue, and syncope; however, in many cases additional tests are required. Increased markers of myocardial necrosis, nonspecific ST segment and T wave changes in the electrocardiogram, global hypokinesia and pericardial effusion in the echocardiogram, as well as histological changes in the biopsy are used as criteria for the diagnosis of myocarditis.(16,17) Moreover, in the absence of evidence of coronary artery disease, increased cardiac troponin I levels may suggest the occurrence of myocarditis, since this marker has high specificity for the diagnosis of myocarditis. (17) The pathogenesis of this involvement may reflect a process of viral replication and dissemination through the blood or lymphatic system of the respiratory tract. Moreover, it may be associated with the infectious process triggered by SARS-CoV-2, which characteristically induces an exaggerated inflammatory response capable of causing myocardial injury. (18) Furthermore, during pulmonary infection, fever and tachycardia increase oxygen demand by cardiac tissue. However, gas exchange impaired by continuous blood flow to lung regions of low ventilation causes a ventilation-perfusion mismatch resulting in blood hypoxemia, and consequently in worsening oxygenation of cardiac tissue. (19)
Yokoo et al.,(7) presented the case of a patient over 80 years old with a history of hypertension and ischemic stroke. Laboratory tests showed high levels of troponin T, electrocardiogram showed no signs of ischemia, and echocardiogram showed an ejection fraction of 35%. This patient underwent a cardiovascular MRI that revealed areas of delayed enhancement with ischemia in the left ventricular base septal wall, in addition to diffuse hypokinesia and impaired global systolic function. (7) Cases of myocarditis associated with COVID-19 have been reported from young to old. Paul et al., (20) described the case of a 35-year-old patient who was overweight as the only cardiovascular risk. In the electrocardiogram of this patient, alterations in repolarization were detected, and laboratory tests showed elevated level of cardiac troponin I of high sensitivity. Cardiac magnetic resonance imaging showed subepicardial enhancement predominantly in the lateral and inferior wall, a typical finding of myocarditis.(20) The two cases described presented patients with pre-existing cardiovascular risk, however, acute myocarditis associated with COVID-19 can also manifest in patients without cardiovascular risk factors. Inciardi et al.,(21) published a case of acute myocarditis in a patient without cardiovascular risk, who presented high-sensitivity troponin T elevation, besides diffuse hypokinesia and reduced ventricular ejection on transthoracic echocardiogram. In this sense, repolarization changes on electrocardiogram, cardiac troponin elevation, as well as detection of left ventricular diastolic impairment on echocardiogram are indicative of myocarditis associated with COVID-19.(21,22)
Patients with cardiac injury associated with SARS-CoV-2 infection have an acute manifestation of COVID-19 with greater severity, characterized by elevated levels of C-reactive protein and creatinine, as well as more intense pulmonary involvement, similar to the patient in this case.(21) The mortality rate is also influenced by the myocardial injury associated with COVID-19, being higher than 50% among patients with cardiac injury in comparison to 5% among those without it, indicating that it is associated with more severe clinical outcomes of COVID-19.(22,23)
In the present reported case, in addition to myocarditis, the patient presented diffuse cerebral edema. Several mechanisms are proposed for the neurological complications induced by COVID-19. The first hypothesis is based on the hematogenous or axonal retrograde pathway with viral accumulation in endothelial cells, smooth muscle cells, pericytes, inflammatory cells, neurons or glia cells. Brain damage may also be related to pneumonia caused by SARS-CoV-2, because when the virus passes through the lung parenchyma, it triggers exaggerated accumulation of neutrophils, increased vascular permeability, and formation of diffuse, interstitial exudates leading to hypoxemia. In the brain, hypoxia promotes increased anaerobic metabolism, promoting vasodilation and cerebral edema.(24) In this sense, the cerebral involvement of the patient in this case probably occurred due to severe hypoxia, which was also associated with the occurrence of circulatory shock. Furthermore, the pneumonia caused by the SARS-CoV-2 infection causes an exaggerated inflammatory response known as "cytokine storm”.(2) This hyperinflammatory state appears in advanced stages of severe COVID-19, causing damage to several organs.(25) The increased levels of cytokines cause destabilization of plaques, which may cause plaque rupture and thus trigger cardiac and cerebral injury. (25,26)
Another point to be analyzed is the presence of dyslipidemia as a comorbidity in the case patient. A meta-analysis of several studies highlighted the existence of a relationship between the presence of dyslipidemia and severe outcomes of COVID-19.(27) After the occurrence of a viral infection, macrophages may interact with cholesterol in atherosclerotic plaques or become involved in inflammasome activation, increasing the secretion of proinflammatory cytokines.(28) Thus, the presence of dyslipidemia may cause endothelial dysfunction and increase the risk of cardiovascular complications. (29)