RT Journal Article SR Electronic T1 SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.24.465626 DO 10.1101/2021.10.24.465626 A1 Giovanny J. Martínez-Colón A1 Kalani Ratnasiri A1 Heping Chen A1 Sizun Jiang A1 Elizabeth Zanley A1 Arjun Rustagi A1 Renu Verma A1 Han Chen A1 Jason R. Andrews A1 Kirsten D. Mertz A1 Alexandar Tzankov A1 Dan Azagury A1 Jack Boyd A1 Garry P. Nolan A1 Christian M. Schürch A1 Matthias S. Matter A1 Catherine A. Blish A1 Tracey L. McLaughlin YR 2021 UL http://biorxiv.org/content/early/2021/10/25/2021.10.24.465626.abstract AB The COVID-19 pandemic, caused by the viral pathogen SARS-CoV-2, has taken the lives of millions of individuals around the world. Obesity is associated with adverse COVID-19 outcomes, but the underlying mechanism is unknown. In this report, we demonstrate that human adipose tissue from multiple depots is permissive to SARS-CoV-2 infection and that infection elicits an inflammatory response, including the secretion of known inflammatory mediators of severe COVID-19. We identify two cellular targets of SARS-CoV-2 infection in adipose tissue: mature adipocytes and adipose tissue macrophages. Adipose tissue macrophage infection is largely restricted to a highly inflammatory subpopulation of macrophages, present at baseline, that is further activated in response to SARS-CoV-2 infection. Preadipocytes, while not infected, adopt a proinflammatory phenotype. We further demonstrate that SARS-CoV-2 RNA is detectable in adipocytes in COVID-19 autopsy cases and is associated with an inflammatory infiltrate. Collectively, our findings indicate that adipose tissue supports SARS-CoV-2 infection and pathogenic inflammation and may explain the link between obesity and severe COVID-19.One sentence summary Our work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.Competing Interest StatementCAB is on the Scientific Advisory Boards of Catamaran Bio and DeepCell. CMS is on the Scientific Advisory Board of and has received research funding from Enable Medicine, Inc., both outside the current work. MSM has served as a consultant for Novartis and Glaxo Smith Kline and received speaker's honoraria from ThermoFisher and Merck, all outside the current work.