Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients

Abstract

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.

COVID‐19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances

“…The proinflammatory cytokines and chemokines, such as IL‐6, IL‐8, tumour necrosis factor (TNF), IL‐17, IL‐12, IL‐1, IP‐10, MCP‐1, and CCL5, were generally increased with higher BMI. 27 , 28 , 36 , 40 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 Furthermore, high levels of IL‐10, an anti‐inflammatory cytokine, appear to be a hallmark of hyperinflammation during severe SARS‐CoV‐2 infection, 57 , 58 and some studies included in this review observed that IL‐10 levels predict poor outcomes in COVID‐19 patients with obesity. 32 , 51 In an attempt to reduce the high COVID‐19 mortality rates due to a cytokine storm, intensive research is underway examining the use of anti‐inflammatory drugs.…”

“… 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 Cell count of the innate immunity was altered in infected patients with a higher BMI in several studies. 29 , 33 , 34 , 35 , 36 The frequency of dendritic cells and monocytes was negatively correlated with BMI in aged COVID‐19 patients, 36 while natural killer (NK) cells decreased with BMI in young COVID‐19 patients. 36 In general, the neutrophil‐to‐lymphocyte ratio (NLR) is positively associated with adiposity and severity in COVID‐19‐positive patients.…”

“… 29 , 33 , 34 , 35 , 36 The frequency of dendritic cells and monocytes was negatively correlated with BMI in aged COVID‐19 patients, 36 while natural killer (NK) cells decreased with BMI in young COVID‐19 patients. 36 In general, the neutrophil‐to‐lymphocyte ratio (NLR) is positively associated with adiposity and severity in COVID‐19‐positive patients. 25 , 30 , 31 In contrast, the lymphocyte count significantly dropped in patients with obesity as compared to those without obesity, and this percentage was significantly associated with death in patients with obesity in univariate and multivariate analyses.…”

“…One study among the articles found in the present review reported a positive correlation between CD4 + central memory T cells and BMI in infected aged patients, while CD8 + cells secreting IFN‐γ correlated negatively with BMI in infected young patients. 36 Contrary to total CD4 + cells, which drop sharply in the infection, memory CD4 + cells are effectively formed in COVID‐19 patients and readily stimulated in vitro. 134 Like CD4 + cells, the CD8 + cell count is negatively associated with the severity of infection.…”

“…One study showed that BMI in COVID‐19 patients correlated with dendritic cells and central memory CD4 + T cells, two important cell types in the immune response following immunization. 36 Considering the antibody response specifically, individuals with obesity may present a unique humoral response with higher antibody titers but lower protection, as discussed above. Previous reports on the vaccination of patients with obesity have also observed mixed results, with BMI either negatively associated with efficacy and antibody levels or having no relationship with these parameters.…”