SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19

Author:

Martínez-Colón Giovanny J.,Ratnasiri Kalani,Chen Heping,Jiang Sizun,Zanley Elizabeth,Rustagi ArjunORCID,Verma Renu,Chen Han,Andrews Jason R.,Mertz Kirsten D.,Tzankov AlexandarORCID,Azagury Dan,Boyd Jack,Nolan Garry P.,Schürch Christian M.,Matter Matthias S.,Blish Catherine A.ORCID,McLaughlin Tracey L.

Abstract

AbstractThe 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 summaryOur work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.

Publisher

Cold Spring Harbor Laboratory

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