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

Martinez-Colon, G. J.; Ratnasiri, K.; Chen, H.; Jiang, S.; Zanley, E.; Rustagi, A.; Verma, R.; Andrews, J. R.; Mertz, K.; Tzankov, A.; Azagury, D.; Boyd, J.; Nolan, G. P.; Schürch, C. M.; Matter, M. S.; Blish, C. A.; McLaughlin, T. L.

doi:10.1101/2021.10.24.465626

bioRxiv · 10.1101/2021.10.24.465626

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

Martinez-Colon, G. J.·Ratnasiri, K.·Chen, H.·Jiang, S.·Zanley, E.·Rustagi, A.·Verma, R.·Andrews, J. R.·Mertz, K.·Tzankov, A.·Azagury, D.·Boyd, J.·Nolan, G. P.·Schürch, C. M.·Matter, M. S.·Blish, C. A.·McLaughlin, T. L.

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Abstract

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

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Martinez-Colon, G. J., Ratnasiri, K., Chen, H., Jiang, S., Zanley, E., Rustagi, A., Verma, R., Andrews, J. R., Mertz, K., Tzankov, A., Azagury, D., Boyd, J., Nolan, G. P., Schürch, C. M., Matter, M. S., Blish, C. A., McLaughlin, T. L.. 2021-10-25. SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19. https://doi.org/10.1101/2021.10.24.465626

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