Obesity Is Associated with Attenuated Tissue Immunity in COVID-19
| العنوان: | Obesity Is Associated with Attenuated Tissue Immunity in COVID-19 |
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| المؤلفون: | Guo, Shuang A, Bowyer, Georgina S, Ferdinand, John R, Maes, Mailis, Tuong, Zewen K, Gillman, Eleanor, Liao, Mingfeng, Lindeboom, Rik GH, Yoshida, Masahiro, Worlock, Kaylee, Gopee, Hudaa, Stephenson, Emily, Gao, Catherine A, Lyons, Paul A, Smith, Kenneth GC, Haniffa, Muzlifah, Meyer, Kerstin B, Nikolić, Marko Z, Zhang, Zheng, Wunderink, Richard G, Misharin, Alexander V, Dougan, Gordon, Navapurkar, Vilas, Teichmann, Sarah A, Conway Morris, Andrew, Clatworthy, Menna R |
| المساهمون: | Guo, Shuang A [0000-0002-1712-9180], Bowyer, Georgina S [0000-0002-2058-4045], Ferdinand, John R [0000-0003-0936-0128], Maes, Mailis [0000-0002-0266-6557], Tuong, Zewen K [0000-0002-6735-6808], Gillman, Eleanor [0000-0002-4221-7270], Lindeboom, Rik GH [0000-0002-3660-504X], Yoshida, Masahiro [0000-0002-3521-5322], Worlock, Kaylee [0000-0002-5656-7634], Gopee, Hudaa [0000-0001-8507-5682], Stephenson, Emily [0000-0002-4244-4019], Gao, Catherine A [0000-0001-5576-3943], Lyons, Paul A [0000-0001-7035-8997], Smith, Kenneth GC [0000-0003-3829-4326], Haniffa, Muzlifah [0000-0002-3927-2084], Meyer, Kerstin B [0000-0001-5906-1498], Nikolić, Marko Z [0000-0001-6304-6848], Zhang, Zheng [0000-0002-3544-1389], Wunderink, Richard G [0000-0002-8527-4195], Misharin, Alexander V [0000-0003-2879-3789], Dougan, Gordon [0000-0003-0022-965X], Navapurkar, Vilas [0000-0002-3610-3568], Teichmann, Sarah A [0000-0002-6294-6366], Conway Morris, Andrew [0000-0002-3211-3216], Clatworthy, Menna R [0000-0002-3340-9828], Apollo - University of Cambridge Repository |
| المصدر: | American Journal of Respiratory and Critical Care Medicine. 207:566-576 |
| بيانات النشر: | American Thoracic Society, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Adult, Pulmonary and Respiratory Medicine, obesity, Pediatric Obesity, SARS-CoV-2, COVID-19, Critical Care and Intensive Care Medicine, single-cell RNA sequencing, type-I interferon, Interferon Type I, Leukocytes, Mononuclear, bronchoalveolar lavage, Humans, Child, Lung |
| الوصف: | Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. 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 obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset. |
| وصف الملف: | application/pdf |
| تدمد: | 1535-4970 1073-449X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e06241f4fda7bfb6aa0e6b3d8366813Test https://doi.org/10.1164/rccm.202204-0751ocTest |
| رقم الانضمام: | edsair.doi.dedup.....3e06241f4fda7bfb6aa0e6b3d8366813 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354970 1073449X |
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