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Sci Transl Med . SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages

tetano

Editor, Senior Moderator
Sci Transl Med


. 2022 Sep 22;eabm9151.
doi: 10.1126/scitranslmed.abm9151. Online ahead of print.
SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages


Giovanny J Martínez-Colón[SUP] 1 [/SUP], Kalani Ratnasiri[SUP] 2 [/SUP], Heping Chen[SUP] 1 [/SUP], Sizun Jiang[SUP] 3 4 [/SUP], Elizabeth Zanley[SUP] 1 [/SUP], Arjun Rustagi[SUP] 1 [/SUP], Renu Verma[SUP] 1 [/SUP], Han Chen[SUP] 3 [/SUP], Jason R Andrews[SUP] 1 [/SUP], Kirsten D Mertz[SUP] 5 [/SUP], Alexandar Tzankov[SUP] 6 [/SUP], Dan Azagury[SUP] 7 [/SUP], Jack Boyd[SUP] 8 [/SUP], Garry P Nolan[SUP] 3 [/SUP], Christian M Schürch[SUP] 9 [/SUP], Matthias S Matter[SUP] 6 [/SUP], Catherine A Blish[SUP] 1 2 10 [/SUP], Tracey L McLaughlin[SUP] 1 [/SUP]



Affiliations

Abstract

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.
 
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