Obesity and severe coronavirus disease 2019: molecular mechanisms, paths forward, and therapeutic opportunities

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to have higher pathogenicity among patients with obesity. Obesity, termed as body mass index greater than 30 kg/m 2 , has now been demonstrated to be important comorbidity for disease severity during coronavirus disease 2019 (COVID-19) pandemic and associated with adverse events. Unraveling mechanisms behind this phenomenon can assist scientists, clinicians, and policymakers in responding appropriately to the COVID-19 pandemic. In this review, we systemically delineated the potential mechanistic links between obesity and worsening COVID-19 from altered physiology, underlying diseases, metabolism, immunity, cytokine storm, and thrombosis. Problematic ventilation caused by obesity and preexisting medical disorders exacerbate organ dysfunction for patients with obesity. Chronic metabolic disorders, including dyslipidemia, hyperglycemia, vitamin D deficiency, and polymorphisms of metabolism-related genes in obesity, probably aid SARS-CoV-2 intrusion and impair antiviral responses. Obesity-induced inadequate antiviral immunity (interferon, natural killer cells, invariant natural killer T cell, dendritic cell, T cells, B cell) at the early stage of SARS-CoV-2 infection leads to delayed viral elimination, increased viral load, and expedited viral mutation. Cytokine storm, with the defective antiviral immunity, probably contributes to tissue damage and pathological progression, resulting in severe symptoms and poor prognosis. The prothrombotic state, driven in large part by endothelial dysfunction, platelet hyperactivation, hypercoagulability, and impaired fibrinolysis in obesity, also increases the risk of severe COVID-19. These mechanisms in the susceptibility to severe condition also open the possibility for host-directed therapies in population with obesity. By bridging work done in these fields, researchers can gain a holistic view of the paths forward and therapeutic opportunities to break the vicious cycle of obesity and its devastating complications in the next emerging pandemic.

Evaluation of the Potential Risk of Mortality from SARS-CoV-2 Infection in Hospitalized Patients According to the Charlson Comorbidity Index

“…Apparently, humoral immunity is not affected, and people with diabetes mellitus have deficits in neutrophil function and alterations in the phenomena of chemotaxis, adhesion, and phagocytosis and also in the intracellular destruction of pathogenic microorganisms [ 55 ]. Patients with T2DM usually have an excess of adipose tissue, which, according to pathophysiological processes, can trigger an alteration of glycemic homeostasis, produce some important alterations such as chronic inflammatory state and chronic hyperglycemia, which cause a negative effect on patients with respect to immunity and make them more susceptible to infections—in this case, to the infection caused by SARS-CoV-2 [ 56 , 57 ].…”

“…The molecular mechanisms associated with SARS-CoV-2 infection involves an increase in inflammation, leading to an increase in cytokines (cytokine storm) in patients with COVID-19 [ 30 ], mainly manifested by an increase in interleukin IL-2, IL-7, INFγ, and TNFα, leading to suppression of NF-kB activity, resulting in decreased expression of COX-2 [ 31 ]. Among all interleukins, IL-6 was found to be associated with highly pathogenic SARS-CoV-2 infection, due to enhanced virus replication mainly in the lower respiratory tract [ 32 , 57 ] ( Figure 2 ).…”

“…Impaired antiviral immunity, leaky SARS-CoV-2 infections, and excessive macrophage infiltration together contribute to uncontrolled cytokine storm, promoting the development of immunopathology such as pulmonary edema and hyaline membrane. The predisposition to a prothrombotic state in COVID-19 is associated with chronical conditions, driven largely by endothelial damage, platelet hyperactivation, hypercoagulability, hyperinflammation, and impaired fibrinolysis and poor outcomes [ 9 , 30 , 31 , 32 , 57 ]. CHO: cholesterol; G: glycosylated; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; COVID-19: coronavirus disease 2019.…”

Use of steroids in COVID-19 patients: A meta-analysis

“…Other laboratory blood tests such as C-reactive protein (CRP) level, D-dimer, complete blood count (CBC) is also done to know about inflammatory and coagulation level of the individuals. It has been observed that patients with comorbid conditions like diabetes, obesity, hypertension, etc are more likely to get into serious conditions ( Rahman et al, 2021 ; Yan et al, 2021 ). Many researchers across the globe are working on the development of new chemical entities (NCEs) against this infection, however, no specific drugs are available in the market for its treatment so far ( Singhal, 2020 ).…”

Long non-coding RNAs in Sus scrofa ileum under starvation stress

“…The World Health Organization (WHO) reports that since 1975, the number of obese people in the world has grown nearly three-fold, and currently, nearly 20 million adults are overweight or obese [1]. Obesity not only affects one's physical appearance but also causes various diseases [2] that burden the economy and the medical and health infrastructure. At present, popular methods of weight loss include dieting, targeted drug therapy, and surgical liposuction.…”