Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic – obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipokines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients.

“HIIT the Inflammation”: Comparative Effects of Low-Volume Interval Training and Resistance Exercises on Inflammatory Indices in Obese Metabolic Syndrome Patients Undergoing Caloric Restriction

“…If obesity is accompanied by other cardiometabolic risk factors, such as hypertension, high storage of visceral fat, hyperglycemia, or dyslipidemia (i.e., the metabolic syndrome, MetS), the risk of serious health issues and premature mortality is further substantially increased [ 3 , 4 ]. During the ongoing COVID-19 pandemic, it has also been observed, for example, that patients with preexisting obesity and cardiometabolic risk factors exhibit an increased likelihood for a severe or fatal disease course after a SARS CoV-2 infection [ 5 , 6 , 7 ], which currently illustrates the aggravated health risk in obese MetS populations.…”

Polycystic ovary syndrome and risks for COVID-19 infection: A comprehensive review

“…Adipose tissue is also a target and reservoir of SARS-CoV-2 [69,70]. The increased risk of severe COVID-19 in "Obesity" is well established [71][72][73][74][75]; the risks are higher for hospitalization and death [73,76,77]. The risk was estimated to be three-fold higher than normal-weight individuals [78].…”

“…In addition, obesity is associated with IR, leading to immune dysregulation characterized by amplified immune responses [138,139], making the immune system more vulnerable to infections [140]. Increased levels of proinflammatory cytokines, NK cells, and mucosal-associated invariant T cells in obesity are also implicated in the pathogenesis of COVID-19 [73,141,142]. Additionally, higher proinflammatory dipeptidyl peptidase4 (DPP-4), and consequent hyperinsulinemia independently increase the risk of COVID-19 in obesity [143].…”

Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues

“…Indeed, low-density lipoproteins (LDL) with smaller size and more density have greater atherogenicity then larger counterparts due to several specific physico-chemical and metabolic properties, including prolonged residency time in plasma because of reduced affinity to LDL receptor, greater entry and retention into the arteries as well as enhanced oxidative susceptibility [13]. Several authors have emphasized that obesity-related and diabetes-related inflammation and endothelial dysfunction have a crucial impact on disease severity in COVID-19 patients [14,15] and, very interestingly, it has been recently shown that low concentrations of high-density lipoproteins (HDL) together with elevated levels of triglycerides predict COVID-19 severity [16]. These two lipid altertations are usually accompanied by the predominance of small, dense LDL, constituting the so-called lipid triad or atherogenic lipoprotein phenotype [17], a lipid trait that is very common in patients at high cardiovascular risk and more evident is some ethnicities [18][19][20][21][22].…”