Abstract and Introduction
Obesity is associated with an increase in morbidity and mortality from coronavirus disease 2019 (COVID-19). The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for severe acute respiratory syndrome coronavirus 2 entry by overexpression of viral receptors [angiotensin-converting enzyme 2 and dipeptidyl peptidase 4]. Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more proinflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyperimmune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells, and other cell types (endothelial cells and platelets, etc) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.
Coronavirus disease 2019 (COVID-19) is an infectious diseases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified in 2019. As of February 1, 2022, the virus and its variants have infected more than 377 million people with 5.7 million deaths worldwide (https://coronavirus.jhu.edu/map.html). The COVID-19 pandemic has generated a huge challenge to the global healthcare community due to the high mortality rate. Although the infection and mortality have been effectively reduced by virus-targeting vaccinations, the threat remains serious as current vaccinations may lose efficacy to emerging mutant strains of virus, and a large portion of world's population remains unvaccinated. It is generally accepted that multiorgan failure is a major cause of the high mortality rate in COVID-19 with cytokine storm as the primary underlying event.[1,2]
Obesity is a well-established risk factor for severe COVID-19 with high mortality,[3,4] which was first reported in April 2020 and currently supported by epidemiological data from the World Health Organization (https://ourworldindata.org/). Based on World Health Organization data in 2016, obesity has become a pandemic, with 39% of adults (age > 18 years) being overweight or obese worldwide, leading to 4.7 million premature deaths each year (https://www.who.int/). The combination of the COVID-19 and obesity pandemics has resulted in a significant increase in the death rate in COVID-19 patients. The underlying mechanism linking obesity to the high death rate remains to be established; however, the chronic inflammation and tissue structure changes derived from obesity appear to be the major factors. For example, obesity may reduce the function of the respiratory system by complications, such as asthma, obstructive sleep apnea, and chronic obstructive pulmonary disease.[5–7] The same applies to the H1N1 influenza virus infection.
In obesity, adipose tissue expansion induces multiple structural and functional changes in the body, which contribute to the development of severe COVID-19[8,9] (Figure 1). The cellular and molecular events of adipose tissue dysfunction leading to severe COVID-19 will be discussed in this review.
J Clin Endocrinol Metab. 2022;107(7):1799-1811. © 2022 Endocrine Society