Summary
Justification:
Obesity affects 40% of American adults, is associated with a pro-inflammatory 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.
Goals:
To determine the impact of obesity on respiratory tract immunity in COVID-19 throughout human life.
Methods:
We analyzed BAL single-cell transcriptomes in three cohorts of adults ventilated 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 peripheral blood mononuclear cells in an independent cohort of adults with COVID-19 (n = 42), comparing obese and non-obese subjects.
Measurements and main results:
Surprisingly, we found that obese adult subjects had immune or pulmonary inflammatory responses. dimmed in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in nearly all subsets of immune and lung epithelial cells, and decreased 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 SARS-CoV-2 patients. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of the IFN-α and IFN-γ response genes.
Conclusions:
These findings show attenuated tissue immune responses in obese COVID-19 patients, with implications for treatment stratification, supporting the targeted application of inhaled recombinant type I IFNs in this vulnerable subset.
