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) >30m 2 ) and non-obese (N-Ob, BMI <30m 2 ). 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.
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SciScore for 10.1101/2022.01.14.475727: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: The use of discard samples surplus to that required for clinical testing, and anonymised data review were conducted under the consent waiver granted by Leeds West NHS Research Ethics Committee (ref: 20/YH/0152).
IRB: The use of discard samples surplus to that required for clinical testing, and anonymised data review were conducted under the consent waiver granted by Leeds West NHS Research Ethics Committee (ref: 20/YH/0152).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Samples were processed on a Fortessa flow cytometer (Becton Dickinson, Basel, Switzerland) … SciScore for 10.1101/2022.01.14.475727: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: The use of discard samples surplus to that required for clinical testing, and anonymised data review were conducted under the consent waiver granted by Leeds West NHS Research Ethics Committee (ref: 20/YH/0152).
IRB: The use of discard samples surplus to that required for clinical testing, and anonymised data review were conducted under the consent waiver granted by Leeds West NHS Research Ethics Committee (ref: 20/YH/0152).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Samples were processed on a Fortessa flow cytometer (Becton Dickinson, Basel, Switzerland) and data analysed using Flowjo version 10. Flowjosuggested: (FlowJo, RRID:SCR_008520)The data were acquired from Gene Expression Omnibus (GEO) database under accession codes GSE145926 and GSE155249, respectively. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Re-integration of structural cells, macrophages, T / NK cells, and B cells: Major cell types including structural cells, macrophages, T / NK cells, and B cells were re-clustered with Seurat (4.0.4), followed by removal of batch effect across different patients with harmony (1.0). Seuratsuggested: (SEURAT, RRID:SCR_007322)Gene set enrichment analysis (GSEA): clusterProfiler36 (3.18.1) was used to perform GSEA. Gene set enrichment analysissuggested: (Gene Set Enrichment Analysis, RRID:SCR_003199)Hallmark gene sets in msigdbr (7.4.1) and enricher function in clusterProfiler were used for gene functional annotation. clusterProfilersuggested: (clusterProfiler, RRID:SCR_016884)Calculation of the cytokine module score: The module score was calculated using AddModuleScore function in Seurat with the cytokine and chemokine gene set from KEGG pathway. KEGGsuggested: (KEGG, RRID:SCR_012773)Briefly, the normalized counts and meta data extracted from Seurat objects were applied for the statistical analysis from CellPhoneDB in python 3.8.8. CellPhoneDBsuggested: (CellPhoneDB, RRID:SCR_017054)pythonsuggested: (IPython, RRID:SCR_001658)Visualization: Plotting was performed using ggplot2 (3.3.5). ggplot2suggested: (ggplot2, RRID:SCR_014601)Heatmap was generated using pheatmap (1.0.12). pheatmapsuggested: (pheatmap, RRID:SCR_016418)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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