Obesity associated with attenuated tissue immune cell responses in COVID-19

Guo, S. A.; Bowyer, G. S.; Ferdinand, J. R.; Maes, M.; Tuong, Z. K.; Gilman, E.; Liao, M.; Lindeboom, R. G. H.; Yoshida, M.; Worlock, K.; Gopee, H.; Stephenson, E.; Lyons, P. A.; Smith, K. G. C.; Haniffa, M.; Meyer, K. B.; Nikolic, M. Z.; Zhang, Z.; Wunderink, R. G.; Misharin, A. V.; Dougan, G.; Navapurkar, V.; Teichmann, S. A.; Morris, A. C.; Clatworthy, M. R.

doi:10.1101/2022.01.14.475727

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bioRxiv · 10.1101/2022.01.14.475727

Obesity associated with attenuated tissue immune cell responses in COVID-19

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Abstract

Obesity is common and associated with more severe COVID-19, proposed to be in part related to an adipokine-driven pro-inflammatory state. Here we analysed single cell transcriptomes from bronchiolar lavage in three adult cohorts, comparing obese (Ob, body mass index (BMI) >30m2) and non-obese (N-Ob, BMI <30m2). Surprisingly, we found that Ob subjects had attenuated lung immune/inflammatory responses in SARS-CoV-2 infection, with decreased expression of interferon (IFN), IFN{gamma} and tumour necrosis factor (TNF) alpha response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Analysis of peripheral blood immune cells in an independent adult cohort showed a similar, but less marked, reduction in type I IFN and IFN{gamma} response genes, as well as decreased serum IFN, in Ob patients with SARS-CoV-2. Nasal immune cells from Ob children with COVID-19 also showed reduced enrichment of IFN and IFN{gamma} response genes. Altogether, these findings show blunted tissue immune responses in Ob COVID-19 patients, with clinical implications.

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Guo, S. A., Bowyer, G. S., Ferdinand, J. R., Maes, M., Tuong, Z. K., Gilman, E., Liao, M., Lindeboom, R. G. H., Yoshida, M., Worlock, K., Gopee, H., Stephenson, E., Lyons, P. A., Smith, K. G. C., Haniffa, M., Meyer, K. B., Nikolic, M. Z., Zhang, Z., Wunderink, R. G., Misharin, A. V., Dougan, G., Navapurkar, V., Teichmann, S. A., Morris, A. C., Clatworthy, M. R.. 2022-01-18. Obesity associated with attenuated tissue immune cell responses in COVID-19. https://doi.org/10.1101/2022.01.14.475727

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