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

ABSTRACT

RATIONALE Obesity affects 40% of US adults, is associated with a pro-inflammatory state, and presents a significant risk factor for the development of severe COVID-19. To date, there is limited information on how obesity might affect immune cell responses in SARS-CoV-2 infection. OBJECTIVES: To determine the impact of obesity on respiratory tract immunity in COVID-19 across human lifespan. METHODS: We analysed single cell transcriptomes from bronchiolar lavage in three ventilated adult cohorts with (n=24) or without COVID-19 (n=9), from nasal immune cells in children with (n=14) or without COVID-19 (n=19), and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n=42), comparing obese (Ob) and non-obese subjects (N-Ob). MEASUREMENTS AND MAIN RESULTS: Surprisingly, we found that adult 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. 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. CONCLUSIONS: These findings show blunted tissue immune responses in Ob COVID-19 patients, with implications for treatment stratification, supporting the specific application of inhaled recombinant type I IFNs in this vulnerable subset. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http//creativecommons.org/licenses/by-nc-nd/4.0/).