Obesity and its associated inflammatory cytokines pose significant risk factors for COVID-19 outcomes

Abstract

The incidence of overweight, obesity and non-alcoholic fatty liver disease (NAFLD) in Western society have increased to epidemic proportions in the past decade and are now recognized as significant progressive comorbidities contributing to complications of COVID-19. Adiposity reflects an imbalance in energy homeostasis, where cumulative energy intake chronically exceeds net energy expenditure often associated with Insulin resistance (IR) and other endocrinopathies which further impairs parameters of energy balance and expenditure. A primary function of white adipose tissues (WAT) is nutritionally and hormonally mediated lipogenesis and lipid storage in the form of triglycerides, derived from dietary or de novo substrates. Central adiposity, including visceral adipose depots is typically associated with chronic inflammation and endocrine dysregulation including elevations in plasma insulin, amylin, and hyperlipidemia, a suppressed immune response, and elevations in markers of inflammation in peripheral tissues, which are contributory to the progression of the cardiovascular, renal, and other significant comorbid sequela that often follow. Multiple mechanisms are operative in obesity that contribute to the magnitude of severity of COVID-19 illness. 1: The SARS-CoV-1 can infect multiple organ systems that contain ACE2 receptors, including WAT; 2. The SARS-CoV-2 virus contains abundant viral spike proteins compatible with the ACE2 receptors of WAT, enabling the efficient uptake of COVID-19 viral particles; 3: WAT secretes the inflammatory cytokines TNF, IL-6, and others, augmented by adipocytokines leptin and resistin, which together facilitate the creation of an enhanced inflammatory state combined in concert with the suppressed immune state; 4: WAT secretes leptin, TNFα, CXCL-10 and other inflammatory adipokines that are common factors in central obesity have been correlated with the severity of COVID-19 in obese individuals, and 5: the cytokine IL-6 from WAT acts as a primary mediator of the cytokine storm inflammatory response which typically leads to the development of an acute respiratory distress syndrome (ARDS) often with dire consequences in later stages of COVID-19. NAFLD also correlates with hyperlipidemia and the severity of COVID-19 in a similar manner. Thus, the inflammatory markers and the lipogenic characteristics of IR, excess adiposity, chronic inflammation, and related sequelae are significant opportunistic contributors to the magnitude of severity and outcome of the morbidity and mortality observed in COVID-19 illness. The purpose of this editorial review is to present an overview of the contributions of obesity and its endocrinologic and inflammatory pathophysiologic sequelae on COVID-19 illness.