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.

Low-grade inflammation, CoVID-19, and obesity: clinical aspect and molecular insights in childhood and adulthood

“…Morbidity and mortality from CoVID-19 are further increased in subjects with obesity with visceral adiposity and ectopic fat deposition [ 60 ]. Therefore, individuals with obesity are assumed to develop more severe CoVID-19 disease than normal-weight individuals, regardless of gender, age, and existence of associated comorbidities [ 61 – 63 ]. Similarly, in a cohort of 200 hospitalized patients, in USA, with CoVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were independently associated with higher in-hospital mortality and in general worse in-hospital outcomes [ 64 ].…”

Obesity associated with attenuated tissue immune cell responses in COVID-19

“…Transcriptomic studies have identified both absent/low and increased IFN response genes in patients with severe or lethal disease, and longitudinal studies revealed a diminished and/or delayed induction of type I IFNs in COVID-19 patients compared with patients with influenza, with an exuberant early TNF/IL6 response 16 . To date, the effect of obesity on immune responses to SARS-CoV-2, particularly tissue responses, has not been considered, although it has been proposed that the elevated leptin associated with obesity might promote an excessive inflammatory response, contributing to the worse outcomes observed in obese patients with COVID-19, with calls for anti-inflammatory therapeutic strategies to be employed in this patient group 17 .…”

Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes

“…Nevertheless, when obesity is present, the low-grade state of inflammation in both omental and subcutaneous adipose tissues often results in impaired glucose metabolism and may contribute to the development of insulin resistance and weight gain. Moreover, obesity and insulin resistance further compromise the already impaired immune systems ( Andrade et al, 2021 ).…”