Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019?

Abstract

Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity-driven predictors of poor COVID-19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID-19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.

Figure 1

Adipose tissue as a reservoir for SARS‐CoV‐2 spread, viral shedding, immune activation, and cytokine amplification. Schematic demonstrating the proposed centrality of adipose tissue in the dissemination of SARS‐CoV‐2 and the ensuing systemic immune activation. Created with Biorender.com. GIT, gastrointestinal tract; IL, interleukin; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor. [Color figure can be viewed at wileyonlinelibrary.com]