Pandemics of the 21st Century: The Risk Factor for Obese People

Abstract

The number of obese adults and children is increasing worldwide, with obesity now being a global epidemic. Around 2.8 million people die annually from clinical overweight or obesity. Obesity is associated with numerous comorbid conditions including hypertension, cardiovascular disease, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, nonalcoholic fatty liver disease, and cancer, and even the development of severe disease after infection with viruses. Over the past twenty years, a number of new viruses has emerged and entered the human population. Moreover, influenza (H1N1)pdm09 virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused pandemics. During pandemics, the number of obese patients presents challenging and complex issues in medical and surgical intensive care units. Morbidity amongst obese individuals is directly proportional to body mass index. In this review, we describe the impact of obesity on the immune system, adult mortality, and immune response after infection with pandemic influenza virus and SARS-CoV-2. Finally, we address the effect of obesity on vaccination.

Keywords: SARS-CoV-2; immune system; influenza; obesity; vaccination.

Figure 1

The impact of obesity on the immune system. In obese individuals, overaccumulated white adipose tissue overexpress adipokines such as leptin adiponectin, C-reactive protein (CRP), and fibrinogen. The leptin receptor is expressed on the surface of T lymphocytes and alters the function of pro-inflammatory IFN-γ and IL-4. Hyperleptinemia is associated with decreased activity of NK cells and lower level of Treg, which lead to a lower amount of sufficient CD4⁺, CD25⁺, and CD127 markers and Foxp3⁺ transcription factor. A decreased concentration of adiponectin alters the function of NK cells. Pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and CCL2 are constantly overexpressed. Lower levels of γδ T cells lead to a reduced production of pro-inflammatory IFN-γ, and alter the adaptive immunity response. Overexpression of CRP impairs the homeostasis between Th1 and Th2 cell subsets, increases the activity of Th17 and Th22, decreases the level of M1 macrophages (M1), increases the level of M2 macrophages (M2), and decreases the number of dendritic cells. Obesity negatively influences the number of B cells, and the production and secretion of pro-inflammatory, anti-inflammatory cytokines, regulatory cytokines, and specific antibodies in infected individuals, which negatively affect disease severity.

Figure 2

Distribution of odds ratios (OR) for intensive care unit administration (ICU), invasive mechanical ventilation (IMV), severe outcome and hospitalization (SO&H), and mortality in patients with obesity after infection with SARS-CoV-2 and influenza virus. The size of the dots corresponds to number of analyzed patients.

Figure 3

The impact of virus infection on the immune response in obese individuals. With influenza infection, the antiviral response and immune disfunction of adaptive immunity are inefficient due to the chronic production of pro-inflammatory cytokines. The production of IFNs I and IFNs III is delayed or increased, and blood peptin upregulates the suppressor of cytokine signaling-3 (SOCS-3), which regulates the function of T and B cells. The reduced amount and activity of γδ T cells leads to a lower production of IFN-γ and reduced T cell diversity. The influenza virus activates assembly of the pyrin domain-containing protein 3 (NLRP3) inflammasome, which supports the autocatalytic processing of pro-caspase-1 and the subsequent cleavage and secretion of pro-inflammatory cytokines IL-1β and IL-18, leading to pyroptosis. The development of cytokine storm results in the overexpression of IL-6 and chemokines CCL2, CCL4, CXCL8, CXCL9, and CXCL10. With SARS-CoV-2 infection, the production of IFN-β and IFN-λ is attenuated, and the level of IFN-γ is very low. Concentrations of CD4⁺ and CD8⁺ T lymphocytes are reduced and the level of Th17 is increased. SARS-CoV-2 upregulates the expression of five cytokines connected to mortality: IL-6, CCL2, CXCL1, CXCL5, and CXCL10. Activation of the NLRP3 inflammasome with increased levels of TNF-α, IFN-γ, IL-1β, IL-8, CCL2, and CXCL10 results in pyroptosis. Overexpression of the ACE receptor plays a crucial role in increased susceptibility to SARS-CoV-2, higher infectivity, and the dysfunction of organs. Both influenza virus and SARS-CoV-2 can infect adipose tissue, which can serve as a virus reservoir, prolonging viral shedding and supporting the origination of new pathogenic variants.