Obesity is associated with a distinct innate immune phenotype in severe COVID-19 patients

Abstract

Abstract Background/Objectives: Obesity is a chronic inflammatory disease that may impair immunity against SARS-Cov-2 in severe disease states. This study investigated whether the innate immune compartment is associated with obesity in severe COVID-19.Methods: This cross-sectional study enrolled twenty-seven ICU COVID-19 patients that were assigned to obese (BMI≥30 kg/m², n=9) and non-obese (BMI<30kg/m², n=18) groups. Thirteen non-obese healthy adults composed the control group. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples and analyzed by flow cytometry to evaluate the frequency and expression patterns of surface receptors associated with innate immune effector responses. sTREM-1 and IL-6 levels from patients’ sera were quantified by ELISA. Results: The frequency of monocytes was negatively correlated with BMI, while NK and neutrophils were positively associated (p<0.05). A reduction of peripheral monocytes was observed in obese patients, and these cells showed a higher expression of PD-L1 than non-obese (p=0.04). HLA-DR expression on CD14+ monocytes was negatively associated with BMI (p=0.03) and total leukocytes (p=0.005). Patients with obesity also demonstrated a higher frequency of NK cells (p=0.01) and a hyperactivated phenotype (CD16+CD182+TREM-1+) in HD neutrophils (p=0.01). This phenotype was positively correlated with total leukocytes (p=0.01) and negatively correlated with the total numbers of HLA-DR+ monocytes in obese group (p=0.001). An increased expression of CD16 (p=0.01) and TREM-1+ (p=0.005) on mature HD neutrophils was detected in obese patients. In this group, CD16 was negatively correlated with IL-6 levels (p=0.03) and TREM-1+ positively correlated with PD-L1 on neutrophils (p=0.03). Furthermore, sTREM-1 levels correlated with PD-L1 of monocytes and LD neutrophils (p=0.02). Finally, aging may exacerbate cytotoxic and suppressive activity. Conclusion: Our data support that obesity differentially affected innate immune response in severe COVID-19 and highlight immune markers that should be further investigated as predictors for monitoring treatment in severe patients with comorbidities.