Obesity and COVID-19: Mechanistic Insights From Adipose Tissue

Abstract

Obesity is associated with an increase in morbidity and mortality from coronavirus disease 2019 (COVID-19). The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for severe acute respiratory syndrome coronavirus 2 entry by overexpression of viral receptors [angiotensin-converting enzyme 2 and dipeptidyl peptidase 4]. Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more proinflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyperimmune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells, and other cell types (endothelial cells and platelets, etc) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.

Keywords: COVID-19; chronic inflammation; cytokine storm; mitochondrial dysfunction; obesity.