Obesity Is Associated with Attenuated Tissue Immunity in COVID-19.

Abstract

<b>Rationale:</b> 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. <b>Objectives:</b> To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. <b>Methods:</b> We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (<i>n</i> = 24) or without (<i>n</i> = 9) COVID-19 from nasal immune cells in children with (<i>n</i> = 14) or without (<i>n</i> = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (<i>n</i> = 42), comparing obese and nonobese subjects. <b>Measurements and Main Results:</b> 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 <i>IFNG</i> and <i>TNF</i> 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. <b>Conclusions:</b> 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.