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

Shuang A. Guo, Georgina S. Bowyer, View ORCID ProfileJohn R. Ferdinand, Mailis Maes, Zewen K. Tuong, Eleanor Gilman, Mingfeng Liao, Rik G. H. Lindeboom, Masahiro Yoshida, Kaylee Worlock, Huda Gopee, Emily Stephenson, Paul A. Lyons, Kenneth G.C. Smith, Muzlifah Haniffa, View ORCID ProfileKerstin B. Meyer, Marko Z. Nikolić, Zheng Zhang, View ORCID ProfileRichard G. Wunderink, Alexander V. Misharin, Gordon Dougan, Vilas Navapurkar, Sarah A. Teichmann, Andrew Conway-Morris, Menna R. Clatworthy
doi: https://doi.org/10.1101/2022.01.14.475727
Shuang A. Guo
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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Georgina S. Bowyer
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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John R. Ferdinand
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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  • ORCID record for John R. Ferdinand
Mailis Maes
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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Zewen K. Tuong
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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Eleanor Gilman
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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Mingfeng Liao
5Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China
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Rik G. H. Lindeboom
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
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Masahiro Yoshida
6UCL Respiratory, Division of Medicine, University College London, London, UK
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Kaylee Worlock
6UCL Respiratory, Division of Medicine, University College London, London, UK
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Huda Gopee
7Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
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Emily Stephenson
7Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
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Paul A. Lyons
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
8NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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Kenneth G.C. Smith
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
8NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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Muzlifah Haniffa
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
7Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
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Kerstin B. Meyer
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
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Marko Z. Nikolić
6UCL Respiratory, Division of Medicine, University College London, London, UK
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Zheng Zhang
5Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China
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Richard G. Wunderink
9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Alexander V. Misharin
9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Gordon Dougan
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
8NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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Vilas Navapurkar
10John V Farman Intensive Care Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Sarah A. Teichmann
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
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  • For correspondence: mrc38@medschl.cam.ac.uk
Andrew Conway-Morris
10John V Farman Intensive Care Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
11Division of Anaesthesia, University of Cambridge Department of Medicine, Cambridge, UK
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  • For correspondence: mrc38@medschl.cam.ac.uk
Menna R. Clatworthy
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
2Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
3Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK
4Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
8NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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  • For correspondence: mrc38@medschl.cam.ac.uk
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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)α, IFNγ 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 IFNγ response genes, as well as decreased serum IFNα, in Ob patients with SARS-CoV-2. Nasal immune cells from Ob children with COVID-19 also showed reduced enrichment of IFNα and IFNγ response genes. Altogether, these findings show blunted tissue immune responses in Ob COVID-19 patients, with clinical implications.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 18, 2022.
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Obesity associated with attenuated tissue immune cell responses in COVID-19
Shuang A. Guo, Georgina S. Bowyer, John R. Ferdinand, Mailis Maes, Zewen K. Tuong, Eleanor Gilman, Mingfeng Liao, Rik G. H. Lindeboom, Masahiro Yoshida, Kaylee Worlock, Huda Gopee, Emily Stephenson, Paul A. Lyons, Kenneth G.C. Smith, Muzlifah Haniffa, Kerstin B. Meyer, Marko Z. Nikolić, Zheng Zhang, Richard G. Wunderink, Alexander V. Misharin, Gordon Dougan, Vilas Navapurkar, Sarah A. Teichmann, Andrew Conway-Morris, Menna R. Clatworthy
bioRxiv 2022.01.14.475727; doi: https://doi.org/10.1101/2022.01.14.475727
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Obesity associated with attenuated tissue immune cell responses in COVID-19
Shuang A. Guo, Georgina S. Bowyer, John R. Ferdinand, Mailis Maes, Zewen K. Tuong, Eleanor Gilman, Mingfeng Liao, Rik G. H. Lindeboom, Masahiro Yoshida, Kaylee Worlock, Huda Gopee, Emily Stephenson, Paul A. Lyons, Kenneth G.C. Smith, Muzlifah Haniffa, Kerstin B. Meyer, Marko Z. Nikolić, Zheng Zhang, Richard G. Wunderink, Alexander V. Misharin, Gordon Dougan, Vilas Navapurkar, Sarah A. Teichmann, Andrew Conway-Morris, Menna R. Clatworthy
bioRxiv 2022.01.14.475727; doi: https://doi.org/10.1101/2022.01.14.475727

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