Association of the COVID-19 pandemic with changes in objectively measured sedentary behaviour and adiposity.

BACKGROUND: Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors. METHODS: Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes. RESULTS: Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (ß = 3.85, 95% CI 1.22-6.49, P = 0.004) and a decrease in adiponectin level (ß = -0.04, 95% CI -0.06 to -0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA. CONCLUSIONS: The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic.

Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study.

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

Visceral fat inflammation and fat embolism are associated with lung's lipidic hyaline membranes in subjects with COVID-19.

BACKGROUND: Preliminary data suggested that fat embolism could explain the importance of visceral obesity as a critical determinant of coronavirus disease-2019 (COVID-19). METHODS: We performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissue (VAT), lungs and livers of 19 subjects with COVID-19 (COVID-19+), and 23 people without COVID-19 (controls). Human adipocytes (hMADS) infected with SARS-CoV-2 were also studied. RESULTS: Although there were no between-group differences in body-mass-index and adipocytes size, a higher prevalence of CD68+ macrophages among COVID-19+ VAT was detected (p = 0.005) and accompanied by crown-like structures presence, signs of adipocytes stress and death. Consistently, human adipocytes were successfully infected by SARS-CoV-2 in vitro and displayed lower cell viability. Being VAT inflammation associated with lipids spill-over from dead adipocytes, we studied lipids distribution by ORO. Lipids were observed within lungs and livers interstitial spaces, macrophages, endothelial cells, and vessels lumen, features suggestive of fat embolism syndrome, more prevalent among COVID-19+ (p < 0.001). Notably, signs of fat embolism were more prevalent among people with obesity (p = 0.03) independently of COVID-19 diagnosis, suggesting that such condition may be an obesity complication exacerbated by SARS-CoV-2 infection. Importantly, all infected subjects' lungs presented lipids-rich (ORO+) hyaline membranes, formations associated with COVID-19-related pneumonia, present only in one control patient with non-COVID-19-related pneumonia. Importantly, transition aspects between embolic fat and hyaline membranes were also observed. CONCLUSIONS: This study confirms the lung fat embolism in COVID-19+ patients and describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in people with COVID-19 and obesity.

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury.

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

Visceral adiposity, subcutaneous adiposity, and severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis.

BACKGROUND AND AIMS: Body mass index (BMI) has previously been shown to increase mortality and disease severity in patients with COVID-19, but the pooled effect estimate was heterogeneous. Although BMI is widely used as an indicator, it cannot distinguish visceral from subcutaneous fat. This systematic review and meta-analysis aimed to investigate the association between visceral adiposity, subcutaneous fat, and severe COVID-19. METHODS: We performed a systematic literature search using the databases: PubMed, Embase, and EuropePMC. Data on visceral fat area (VTA), subcutaneous fat area (SFA), and total fat area (TFA) were collected. The outcome of interest was severe COVID-19. We used a REML random-effects model to pool the mean differences and odds ratio (OR). RESULTS: There were 5 studies comprising of 539 patients. Patients with severe COVID-19 have a higher VTA (mean difference 41.7 cm2 [27.0, 56.4], p < 0.001; I2: 0%) and TFA (mean difference 64.6 cm2 [26.2, 103.1], p = 0.001; I2: 0%). There was no significant difference in terms of SFA between patients with severe and non-severe COVID-19 (mean difference 9.3 cm2 [-4.9, 23.4], p = 0.199; I2: 1.2%). Pooled ORs showed that VTA was associated with severe COVID-19 (OR 1.9 [1.1, 2.2], p = 0.002; I2: 49.3%). CONCLUSION: Visceral adiposity was associated with increased COVID-19 severity, while subcutaneous adiposity was not. PROSPERO ID: CRD42020215876.

We Should Do More to Offer Evidence-Based Treatment for an Important Modifiable Risk Factor for COVID-19: Obesity.

Observational studies, from multiple countries, repeatedly demonstrate an association between obesity and severe COVID-19, which is defined as need for hospitalization, intensive care unit admission, invasive mechanical ventilation (IMV) or death. Meta-analysis of studies from China, USA, and France show odds ratio (OR) of 2.31 (95% CI 1.3-4.1) for obesity and severe COVID-19. Other studies show OR of 12.1 (95% CI 3.25-45.1) for mortality and OR of 7.36 (95% CI 1.63-33.14) for need for IMV for patients with body mass index (BMI) ≥ 35 kg/m2. Obesity is the only modifiable risk factor that is not routinely treated but treatment can lead to improvement in visceral adiposity, insulin sensitivity, and mortality risk. Increasing the awareness of the association between obesity and COVID-19 risk in the general population and medical community may serve as the impetus to make obesity identification and management a higher priority.

Visceral adipose tissue area predicts intensive care unit admission in COVID-19 patients.

We retrospectively investigated, in 62 consecutive hospitalised COVID-19 patients (aged 70 ± 14 years, 40 males), the prognostic value of CT-derived subcutaneous adipose tissue and visceral adipose tissue (VAT) metrics, testing them in four predictive models for admission to intensive care unit (ICU), with and without pre-existing comorbidities. Multivariate logistic regression identified VAT score as the best ICU admission predictor (odds ratios 4.307-12.842). A non-relevant contribution of comorbidities at receiver operating characteristic analysis (area under the curve 0.821 for the CT-based model, 0.834 for the one including comorbidities) highlights the potential one-stop-shop prognostic role of CT-derived lung and adipose tissue metrics.