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

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.

Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers

“…The theory of viral reservoirs as an explanation for long-COVID symptoms has been put forward because viral antigens or intermediate molecules of viral replication have been detected in long-COVID cases despite negative PCR tests. 17,18,19,20 However, to our knowledge, this is the first evidence of a viral reservoir based on intrahost phylogenetics. These results call for further investigation to determine whether SARS-CoV-2 viral reservoir can be found in immunocompetent patients.…”

Temporal Vascular Endothelial Growth Factor Sub-type gene Switching in SARS-CoV Pathogenesis. Interpretation through in vivo Murine C57BL Models

“…Mortality from severe pulmonary infection is highest among at-risk groups with chronic underlying conditions, including those with obesity and hypertension 1,2 .…”

SARS-CoV-2 fires up inflammation in adipose tissue

“…Interestingly, the authors found evidence that SARS-CoV-2 entry into macrophages might also not be dependent on ACE2 expression. Altogether, the new data by Martínez-Colón and colleagues suggest that adipose tissue could serve as an important target and reservoir for SARS-CoV-2 and that the related local inflammation and possible systemic inflammation might promote severe COVID-19 in people with obesity 3 .…”

“…To understand the mechanisms involved in this relationship, Martínez-Colón and colleagues investigated the targets of SARS-CoV-2 within adipose tissue. Furthermore, they studied how infection might drive subclinical inflammation and functional alterations at the single-cell level 3 by analysing adipose tissue from patients with COVID-19 who had died. They detected SARS-CoV-2 RNA in several adipose depots and, by using RNA in situ hybridization, they also found SARS-CoV-2 in the cytoplasm of adipocytes and an adjacent mononuclear inflammatory infiltrate.…”

“…There is ample evidence that adipose tissue is an important target for SARS-CoV-2 (refs. 3 – 6 ). Interestingly, it might not be adipose tissue per se, but rather specifically lipid-laden adipocytes that enable the virus to infect adipose tissue and to replicate 5 .…”