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.

Increasing adiposity and the presence of cardiometabolic morbidity is associated with increased Covid-19-related mortality: results from the UK Biobank.

BACKGROUND: Although obesity, defined by body mass index (BMI), has been associated with a higher risk of hospitalisation and more severe course of illness in Covid-19 positive patients amongst the British population, it is unclear if this translates into increased mortality. Furthermore, given that BMI is an insensitive indicator of adiposity, the effect of adipose volume on Covid-19 outcomes is also unknown. METHODS: We used the UK Biobank repository, which contains clinical and anthropometric data and is linked to Public Health England Covid-19 healthcare records, to address our research question. We performed age- and sex- adjusted logistic regression and Chi-squared test to compute the odds for Covid-19-related mortality as a consequence of increasing BMI, and other more sensitive indices of adiposity such as waist:hip ratio (WHR) and percent body fat, as well as concomitant cardiometabolic illness. RESULTS: 13,502 participants were tested for Covid-19 (mean age 70 ± 8 years, 48.9% male). 1582 tested positive (mean age 68 ± 9 years, 52.8% male), of which 305 died (mean age 75 ± 6 years, 65.5% male). Increasing adiposity was associated with higher odds for Covid-19-related mortality. For every unit increase in BMI, WHR and body fat, the odds of death amongst Covid19-positive participants increased by 1.04 (95% CI 1.01-1.07), 10.71 (95% CI 1.57-73.06) and 1.03 (95% CI 1.01-1.05), respectively (all p < 0.05). Referenced to Covid-19 positive participants with a normal weight (BMI 18.5-25 kg/m2), Covid-19 positive participants with BMI > 35 kg/m2 had significantly higher odds of Covid-19-related death (OR 1.70, 95% CI 1.06-2.74, p < 0.05). Covid-19-positive participants with metabolic (diabetes, hypertension, dyslipidaemia) or cardiovascular morbidity (atrial fibrillation, angina) also had higher odds of death. CONCLUSIONS: Anthropometric indices that are more sensitive to adipose volume and its distribution than BMI, as well as concurrent cardiometabolic illness, are associated with higher odds of Covid-19-related mortality amongst the UK Biobank cohort that tested positive for the infection. These results suggest adipose volume may contribute to adverse Covid-19-related outcomes associated with obesity.

Nutritional and Behavioral Approaches to Body Composition and Low-Grade Chronic Inflammation Management for Older Adults in the Ordinary and COVID-19 Times.

As more insight is gained into personalized health care, the importance of personalized nutritional and behavioral approaches is even more relevant in the COVID-19 era, in addition to the need for further elucidation regarding several diseases/conditions. One of these concerning body composition (in this context; bone, lean and adipose tissue) is osteosarcopenic adiposity (OSA) syndrome. OSA occurs most often with aging, but also in cases of some chronic diseases and is exacerbated with the presence of low-grade chronic inflammation (LGCI). OSA has been associated with poor nutrition, metabolic disorders and diminished functional abilities. This paper addresses various influences on OSA and LGCI, as well as their mutual action on each other, and provides nutritional and behavioral approaches which could be personalized to help with either preventing or managing OSA and LGCI in general, and specifically in the time of the COVID-19 pandemic. Addressed in more detail are nutritional recommendations for and roles of macro- and micronutrients and bioactive food components; the microbiome; and optimal physical activity regimens. Other issues, such as food insecurity and nutritional inadequacy, circadian misalignment and shift workers are addressed as well. Since there is still a lack of longer-term primary studies in COVID-19 patients (either acute or recovered) and interventions for OSA improvement, this discussion is based on the existing knowledge, scientific hypotheses and observations derived from similar conditions or studies just being published at the time of this writing.

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.

Visceral Adiposity and High Intramuscular Fat Deposition Independently Predict Critical Illness in Patients with SARS-CoV-2.

OBJECTIVE: This study aimed to assess the association between adipose tissue distribution and severity of clinical course in patients with severe acute respiratory syndrome coronavirus 2. METHODS: For this retrospective study, 143 hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) who underwent an unenhanced abdominal computed tomography (CT) scan between January 1, 2020, and March 30, 2020, were included. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with the severity of COVID-19 infection. RESULTS: There were 45 patients who were identified as critically ill. High visceral to subcutaneous adipose tissue area ratio (called visceral adiposity) (odds ratio: 2.47; 95% CI: 1.05-5.98, P = 0.040) and low mean attenuation of skeletal muscle (called high intramuscular fat [IMF] deposition) (odds ratio: 11.90; 95% CI: 4.50-36.14; P < 0.001) were independent risk factors for critical illness. Furthermore, visceral adiposity or high IMF deposition increased the risk of mechanical ventilation (P = 0.013, P < 0.001, respectively). High IMF deposition increased the risk of death (P = 0.012). CONCLUSIONS: COVID-19 patients with visceral adiposity or high IMF deposition have higher risk for critical illness. Therefore, patients with abdominal obesity should be monitored more carefully when hospitalized.