TY - JOUR T1 - Obesity associated with attenuated tissue immune cell responses in COVID-19 JF - bioRxiv DO - 10.1101/2022.01.14.475727 SP - 2022.01.14.475727 AU - Shuang A. Guo AU - Georgina S. Bowyer AU - John R. Ferdinand AU - Mailis Maes AU - Zewen K. Tuong AU - Eleanor Gilman AU - Mingfeng Liao AU - Rik G. H. Lindeboom AU - Masahiro Yoshida AU - Kaylee Worlock AU - Huda Gopee AU - Emily Stephenson AU - Paul A. Lyons AU - Kenneth G.C. Smith AU - Muzlifah Haniffa AU - Kerstin B. Meyer AU - Marko Z. Nikolić AU - Zheng Zhang AU - Richard G. Wunderink AU - Alexander V. Misharin AU - Gordon Dougan AU - Vilas Navapurkar AU - Sarah A. Teichmann AU - Andrew Conway-Morris AU - Menna R. Clatworthy Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/18/2022.01.14.475727.abstract N2 - 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 StatementThe authors have declared no competing interest. ER -