Mechanisms contributing to adverse outcomes of COVID-19 in obesity.

A growing amount of epidemiological data from multiple countries indicate an increased prevalence of obesity, more importantly central obesity, among hospitalized subjects with COVID-19. This suggests that obesity is a major factor contributing to adverse outcome of the disease. As it is a metabolic disorder with dysregulated immune and endocrine function, it is logical that dysfunctional metabolism contributes to the mechanisms behind obesity being a risk factor for adverse outcome in COVID-19. Emerging data suggest that in obese subjects, (a) the molecular mechanisms of viral entry and spread mediated through ACE2 receptor, a multifunctional host cell protein which links to cellular homeostasis mechanisms, are affected. This includes perturbation of the physiological renin-angiotensin system pathway causing pro-inflammatory and pro-thrombotic challenges (b) existent metabolic overload and ER stress-induced UPR pathway make obese subjects vulnerable to severe COVID-19, (c) host cell response is altered involving reprogramming of metabolism and epigenetic mechanisms involving microRNAs in line with changes in obesity, and (d) adiposopathy with altered endocrine, adipokine, and cytokine profile contributes to altered immune cell metabolism, systemic inflammation, and vascular endothelial dysfunction, exacerbating COVID-19 pathology. In this review, we have examined the available literature on the underlying mechanisms contributing to obesity being a risk for adverse outcome in COVID-19.

The Obesity Paradox Predicts the Second Wave of COVID-19 to Be Severe in Western Countries.

While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people's visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots.

The role of visceral adiposity in the severity of COVID-19: Highlights from a unicenter cross-sectional pilot study in Germany.

BACKGROUND AND AIMS: Overall obesity has recently been established as an independent risk factor for critical illness in patients with coronavirus disease 2019 (COVID-19). The role of fat distribution and especially that of visceral fat, which is often associated with metabolic syndrome, remains unclear. Therefore, this study aims at investigating the association between fat distribution and COVID-19 severity. METHODS: Thirty patients with COVID-19 and a mean age of 65.6 ±â€¯13.1 years from a level-one medical center in Berlin, Germany, were included in the present cross-sectional analysis. COVID-19 was confirmed by polymerase chain reaction (PCR) from nasal and throat swabs. A severe clinical course of COVID-19 was defined by hospitalization in the intensive care unit (ICU) and/or invasive mechanical ventilation. Fat was measured at the level of the first lumbar vertebra on routinely acquired low-dose chest computed tomography (CT). RESULTS: An increase in visceral fat area (VFA) by ten square centimeters was associated with a 1.37-fold higher likelihood of ICU treatment and a 1.32-fold higher likelihood of mechanical ventilation (adjusted for age and sex). For upper abdominal circumference, each additional centimeter of circumference was associated with a 1.13-fold higher likelihood of ICU treatment and a 1.25-fold higher likelihood of mechanical ventilation. CONCLUSIONS: Our proof-of-concept study suggests that visceral adipose tissue and upper abdominal circumference specifically increase the likelihood of COVID-19 severity. CT-based quantification of visceral adipose tissue and upper abdominal circumference in routine chest CTs may therefore be a simple tool for risk assessment in COVID-19 patients.

Obesity in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Obesity is common in patients with coronavirus disease 2019 (COVID-19). The effects of obesity on clinical outcomes of COVID-19 warrant systematical investigation. OBJECTIVE: This study explores the effects of obesity with the risk of severe disease among patients with COVID-19. METHODS: Body mass index (BMI) and degree of visceral adipose tissue (VAT) accumulation were used as indicators for obesity status. Publication databases including preprints were searched up to August 10, 2020. Clinical outcomes of severe COVID-19 included hospitalization, a requirement for treatment in an intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality. Risks for severe COVID-19 outcomes are presented as odds ratios (OR) and 95% confidence interval (95%CI) for cohort studies with BMI-defined obesity, and standardized mean difference (SMD) and 95%CI for controlled studies with VAT-defined excessive adiposity. RESULTS: A total of 45, 650 participants from 30 studies with BMI-defined obesity and 3 controlled studies with VAT-defined adiposity were included for assessing the risk of severe COVID-19. Univariate analyses showed significantly higher ORs of severe COVID-19 with higher BMI: 1.76 (95%: 1.21, 2.56, P = 0.003) for hospitalization, 1.67 (95%CI: 1.26, 2.21, P<0.001) for ICU admission, 2.19 (95%CI: 1.56, 3.07, P<0.001) for IMV requirement, and 1.37 (95%CI: 1.06, 1.75, P = 0.014) for death, giving an overall OR for severe COVID-19 of 1.67 (95%CI: 1.43, 1.96; P<0.001). Multivariate analyses revealed increased ORs of severe COVID-19 associated with higher BMI: 2.36 (95%CI: 1.37, 4.07, P = 0.002) for hospitalization, 2.32 (95%CI: 1.38, 3.90, P = 0.001) for requiring ICU admission, 2.63 (95%CI: 1.32, 5.25, P = 0.006) for IMV support, and 1.49 (95%CI: 1.20, 1.85, P<0.001) for mortality, giving an overall OR for severe COVID-19 of 2.09 (95%CI: 1.67, 2.62; P<0.001). Compared to non-severe COVID-19 patients, severe COVID-19 cases showed significantly higher VAT accumulation with a SMD of 0.49 for hospitalization (95% CI: 0.11, 0.87; P = 0.011), 0.57 (95% CI: 0.33, 0.81; P<0.001) for requiring ICU admission and 0.37 (95% CI: 0.03, 0.71; P = 0.035) for IMV support. The overall SMD for severe COVID-19 was 0.50 (95% CI: 0.33, 0.68; P<0.001). CONCLUSIONS: Obesity increases risk for hospitalization, ICU admission, IMV requirement and death among patients with COVID-19. Further, excessive visceral adiposity appears to be associated with severe COVID-19 outcomes. These findings emphasize the need for effective actions by individuals, the public and governments to increase awareness of the risks resulting from obesity and how these are heightened in the current global pandemic.