Validation of the signaling pathways in peripheral blood mononuclear cell (PBMC) samples. (A) Sample demographics of Stephenson and colleagues (25) PBMC samples used in this study. (B) Dot plot of gene set enrichment analysis of most enriched immune pathways within Hallmark gene sets for each T/natural killer (NK)/ILC subpopulation in PBMCs. Mean expression of genes contained in each gene set within each cell type, separated into nonobese versus obese groups, are indicated by color gradients. P values are indicated by dot sizes. (C) Dot plot of gene set enrichment analysis of most enriched immune pathways within Hallmark gene sets for each B/plasma subpopulation in PBMCs. Mean expression of genes contained in each gene set within each cell type, separated into nonobese versus obese groups, are indicated by color gradients. P values are indicated by dot sizes. (D) Mean expression dot plots of transcripts for IFN-γ, IL-6, and TNF-α in myeloid, T, and NK cells in the BAL samples. Expression amounts in each case are indicated by distinct color gradients (green: nonobese without COVID-19; yellow: nonobese with COVID-19; purple: obese without COVID-19; and magenta: obese with COVID-19). Expression percentages are indicated by dot sizes. (E) Mean expression dot plots for IL-6, TNF, and IFN-G in PBMC cell clusters from Stephenson and colleagues (25) grouped according to BMI status. The size of circles corresponds to the fraction of cells expressing each gene, and an increasing gradient from purple to yellow corresponds to an increasing mean expression value (standardized to 0–1 per gene). (F) Serum IFN-α measurements from n = 4 obese and n = 4 nonobese patients from the adult PBMC patient cohort (Stephenson and colleagues [25]). All four Obese samples were below detection limits. BMI = body mass index; cDC = classical dendritic cell; CM = central memory; EM = effector memory; ILC = Innate lymphoid cells; MoAM = monocyte-derived macrophage; N-ob = nonobese; Ob = obese; pDC = plasmacytoid dendritic cell; Tfh = T follicular helper; TNF = tumor necrosis factor; TRAM = tissue-resident macrophage.