Obesity Accompanying COVID‐19: The Role of Epicardial Fat
Lei Zhao
Abstract
To the Editor: With interest, we read the study by Simonnet et al. ((1)), in which important novel evidence is addressed on the fact that obesity is highly frequent among critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Although clinically very relevant, it remains difficult to elucidate the mechanisms by which SARS-CoV-2 severity is increased in the context of obesity. As reported by Katz et al. ((2)), 28% of hospitalized patients with coronavirus disease 2019 (COVID-19) presented with cardiac complications, including myocarditis, arrhythmias, heart failure (HF), and sudden death. Considering that myocardial response in COVID-19 is closely associated with in-hospital mortality, local biological effects on myocardial tissue from epicardial adipose tissue (EAT) warrant further discussion. Among COVID-19 patients included in the study, BMI ≥ 30 kg/m2 and > 35 kg/m2 were more frequent ((1)). BMI is associated with EAT volume. EAT, the metabolically active visceral fat mostly located in atrioventricular and interventricular grooves, is likely to affect the myocardial function from early on in the pathophysiology process. EAT is a rich source of adipokines, including proinflammatory mediators. Accumulation of adipokines secreted from EAT probably play a negative inotropic effect locally and contribute to subsequent inflammatory factor cascade systematically. Cytokine storms and dysfunctional immune systems during COVID-19 accelerate the progression of the disease. The pathological report ((3)) implied an overactivation of T cells, manifested with increased Th17 and high cytotoxicity of CD8 T cells, which indicate the immune dysregulation in COVID-19. It can explain why the elderly are more vulnerable and more likely to develop into critically ill patients; they have a fragile immune system, especially those with underlying disorders. It has been speculated that the inflammatory factor cascade (e.g., tumor necrosis factor and interleukin-6), resulting from dysfunctional host immune response to viral infection, has been linked to negative inotropic effect and subsequent HF decompensation. Conversely, the deterioration of cardiac function contributes to hypoxia and systemic inflammation, both preceeding disease aggravation. Based on current data, SARS-CoV-2 was shown to enter into the host cell through angiotensin converting enzyme2 (ACE2) receptor following the priming of spike protein by host cell proteases ((4)). Beside alveolar cells, ACE2 is also localized to human EAT. Loss of ACE2 increases macrophage polarization to a proinflammatory phenotype in EAT from HF patients. Also, ACE2 and inflammatory cytokines tumor necrosis factor-α and interleukin-6 have been demonstrated to be expressed at higher levels in epicardial fat in heart explants removed from patients with obesity with preserved ejection fraction HF than lean controls ((5)), which provides a rationale for proposing that EAT inflammation could contribute to myocardial complications, such as myocarditis or cardiomyocyte dysfunction, by the virus taking advantage of more ACE2-binding sites for internalization of the virus into adipocytes and then triggering an augmented inflammatory signaling cascade. To date, many critically ill patients with COVID-19 are still hospitalized. Considering that obesity, especially EAT, is an essential component in predicting the progression, we will need to optimize therapeutic strategies, such as appropriate physical exercise and pharmaceutical methods, in order to help disease recovery. The author declared no conflict of interest.