Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Abstract

The coronavirus disease 2019 COVID-19 pandemic is rapidly spreading worldwide and is becoming a major public health crisis. Increasing evidence demonstrates a strong correlation between obesity and the COVID-19 disease. We have summarized recent studies and addressed the impact of obesity on COVID-19 in terms of hospitalization, severity, mortality, and patient outcome. We discuss the potential molecular mechanisms whereby obesity contributes to the pathogenesis of COVID-19. In addition to obesity-related deregulated immune response, chronic inflammation, endothelium imbalance, metabolic dysfunction, and its associated comorbidities, dysfunctional mesenchymal stem cells/adipose-derived mesenchymal stem cells may also play crucial roles in fueling systemic inflammation contributing to the cytokine storm and promoting pulmonary fibrosis causing lung functional failure, characteristic of severe COVID-19. Moreover, obesity may also compromise motile cilia on airway epithelial cells and impair functioning of the mucociliary escalators, reducing the clearance of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Obese diseased adipose tissues overexpress the receptors and proteases for the SARS-CoV-2 entry, implicating its possible roles as virus reservoir and accelerator reinforcing violent systemic inflammation and immune response. Finally, anti-inflammatory cytokines like anti-interleukin 6 and administration of mesenchymal stromal/stem cells may serve as potential immune modulatory therapies for supportively combating COVID-19. Obesity is conversely related to the development of COVID-19 through numerous molecular mechanisms and individuals with obesity belong to the COVID-19-susceptible population requiring more protective measures.

Keywords: COVID-19; adipose-derived mesenchymal stem/stromal cells; cytokine storm; immune response; inflammation; obesity.

Figure 1

The illustration indicates that adipose tissue expresses the receptors ACE2, DPP4, and CD147, and the protease furin for the SARS-CoV-2 entry. These proteins are upregulated in obese adipose tissues accompanied by an enhanced secretion of ACE2 and DPP4 in the circulation of obese patients. Diseased adipose tissues could be targeted by SARS-CoV-2 and serve as its reservoir, as well as an accelerator reinforcing systemic inflammation and immune response, resulting in severe outcome of COVID-19 in obese patients.

Figure 2

A model showing negative effects of obesity on the pulmonary pathogenesis of COVID-19. Obesity-associated aspects, including defective immune response, chronic inflammation, dysfunctional MSCs, compromised ciliated airway epithelial cells, mechanical defects, and pulmonary arterial hypertension, impair the lung defense system against SARS-CoV-2 infection and cause worse outcome of obese COVID-19 patients.

Figure 3

Schematic illustration presenting that obesity negatively impacts the development of COVID-19. Obesity is characterized by various pathological features, including systemic chronic inflammation, deregulated immune response, dysfunctional endothelium, increased comorbidities, and dysfunctional ASCs/MSCs, which fundamentally influence the progression and outcome of COVID-19. Anti-inflammatory cytokine therapies for example anti-IL-6 and administration of MSCs may be useful for supportively treating COVID-19.