The Role of Obesity in the Immunopathogenesis of COVID-19 Respiratory Disease and Critical Illness

Abstract

Coronavirus disease (COVID-19), the clinical syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global health pandemic with substantial morbidity and mortality. COVID-19 has cast a shadow on nearly every aspect of society, straining health systems and economies across the world. Although it is widely accepted that a close relationship exists between obesity, cardiovascular disease, and metabolic disorders on infection, we are only beginning to understand ways in which the immunological sequelae of obesity functions as a predisposing factor related to poor clinical outcomes in COVID-19. As both the innate and adaptive immune systems are each primed by obesity, the alteration of key pathways results in both an immunosuppressed and hyperinflammatory state. The present review will discuss the cellular and molecular immunology of obesity in the context of its role as a risk factor for severe COVID-19, discuss the role of cytokine storm, and draw parallels to prior viral epidemics such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and 2009 H1N1.

Keywords: COVID-19; adaptive; cytokine; innate; obesity.

Figure 1.

Proposed mechanism of obesity-mediated priming and inflammation in coronavirus disease (COVID-19). ARDS = acute respiratory distress syndrome; ER = endoplasmic reticulum; HLH = hemophagocytic lymphohistiocytosis; MCP-1 = monocyte chemoattractant protein-1; NOD = nucleotide-binding and oligomerization domain; RIG-I = retinoic acid-inducible gene I; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TLR = Toll-like receptor.