The Weight of Obesity in Immunity from Influenza to COVID-19

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in December 2019 and rapidly outspread worldwide endangering human health. The coronavirus disease 2019 (COVID-19) manifests itself through a wide spectrum of symptoms that can evolve to severe presentations as pneumonia and several non-respiratory complications. Increased susceptibility to COVID-19 hospitalization and mortality have been linked to associated comorbidities as diabetes, hypertension, cardiovascular diseases and, recently, to obesity. Similarly, individuals living with obesity are at greater risk to develop clinical complications and to have poor prognosis in severe influenza pneumonia. Immune and metabolic dysfunctions associated with the increased susceptibility to influenza infection are linked to obesity-associated low-grade inflammation, compromised immune and endocrine systems, and to high cardiovascular risk. These preexisting conditions may favor virological persistence, amplify immunopathological responses and worsen hemodynamic instability in severe COVID-19 as well. In this review we highlight the main factors and the current state of the art on obesity as risk factor for influenza and COVID-19 hospitalization, severe respiratory manifestations, extrapulmonary complications and even death. Finally, immunoregulatory mechanisms of severe influenza pneumonia in individuals with obesity are addressed as likely factors involved in COVID-19 pathophysiology.

Keywords: COVID-19; immunity; immunopathology; obesity; severe influenza.

Figure 1

Main factors of obesity-related inflammation and metabolic syndrome possibly involved in pathophysiology of respiratory viral infections. (A) changes in adipose tissue architecture with hypertrophic adipocytes, inflammatory infiltrate and fibrosis; (B) the loss of fat storage capacity and altered adipokinesecretionin dysfunctional white adipose tissue; and (C) metabolic endotoxemia resulting from the intestinal endothelial hyperpermeability also contribute to systemic metabolic and immunological complications; leading to (D) systemic low-grade inflammation, metabolic syndrome and increased cardiovascular risk. This syndrome evolves with (E) obesity-associated comorbidities and (F) increased susceptibility to infectious diseases, including Influenza and COVID-19. See the text for details and references.

Figure 2

Obesity and COVID-19. The low-grade systemic inflammation, endothelial dysfunction and procoagulant state in obesity amplify and contribute to COVID-19 immunopathology, such as (A) cytokine storm; (B) immunothrombotic tissue injury; and (C) increased risk for thromboembolic events, including (D) myocardial infarction, pulmonary thromboembolism, among others.