COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

Abstract

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the “cytokine storm” and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

Browning Epicardial Adipose Tissue: Friend or Foe?

“…Furthermore, the authors observed that EAT density was significantly reduced after treatment by dexamethasone, suggesting that EAT could be targeted by anti-inflammatory treatment [97]. Moreover, numerous studies have highlighted the possible implication of EAT in myocardial inflammation through its anatomical and functional relationship with the myocardium [94,98,99]. The EAT inflammatory secretome, such as interleukin-6 (IL-6), cytokine found in excess in severe COVID-19 patients, may be a key element in cardiac complications [98].…”

“…Given that obesity has been identified as an independent risk factor for complications and mortality in coronavirus disease 2019 (COVID-19), great interest has been shown in the involvement of EAT in this disease. EAT would appear to express higher levels of ACE2 than subcutaneous adipose tissue, which could make it a preferred viral reservoir [94]. Several studies have shown that EAT is a major driver of COVID-19 severity [94].…”

“…EAT would appear to express higher levels of ACE2 than subcutaneous adipose tissue, which could make it a preferred viral reservoir [94]. Several studies have shown that EAT is a major driver of COVID-19 severity [94]. Using computed tomography (CT) scans and semi-automatic software, Cosson et al demonstrated that volume was associated with the severity of COVID-19 and with transfer to intensive care unit (ICU) or death [95].…”

Immune Cell Activation in Obesity and Cardiovascular Disease

“…For example, adenoviruses and enteroviruses are cardiotropic and cause direct myocardial injury by infecting cardiomyocytes; parvovirus B19 is vasculotropic and causes inflammation in the endothelial cells; coronaviruses including SARS-CoV2 may cause indirect cytokine-mediated cardiotoxicity [ 44 , 45 •, 46 ]; and immune checkpoint inhibitors used for cancer treatment cause T cell-mediated injury to unknown, presumably self, antigens [ 47 ]. Adipose tissue and systemic immune changes of obesity may contribute to myocardial injury through soluble mediators that act locally (from epicardial adipose tissue surrounding the myocardium) or at a distance (from visceral adipose tissue within the abdomen) [ 48 – 50 ].…”

Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues

“…Investigating such molecular mechanisms at the basis of atherosclerosis formation and progression can help to assess better strategies for proper treatment; for instance, the concomitant management of multiple lipid alterations is able to reduce the risk for cardiovascular events and the rates of progression of atherosclerotic disease [25]. This is particularly true during the current pandemic where we have observed a significant increase in cardiovascular complications in patients with diabetes or obesity [26,27]. In this context, some novel antidiabetic agents, such as glucagon-like peptide (GLP)-1 receptor agonists seems to play a role due to their anti-inflammatory and anti-atherogenic/thrombotic effects [28,29], with a likely direct mechanism against COVID-19 onset and severity [30].…”