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1.
Nutrients ; 14(20)2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2071661

ABSTRACT

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.


Subject(s)
COVID-19 , Respiratory Insufficiency , Humans , Body Mass Index , Interleukin-6 , Obesity/complications , Obesity/pathology , Inflammation/complications , Respiratory Insufficiency/complications , Albumins , Ferritins , Risk Assessment , Intra-Abdominal Fat/pathology , Risk Factors
2.
Nutrients ; 14(18)2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2033075

ABSTRACT

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.


Subject(s)
COVID-19 , Aged , Body Composition/physiology , C-Reactive Protein/metabolism , Female , Humans , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
3.
BMC Geriatr ; 22(1): 686, 2022 08 19.
Article in English | MEDLINE | ID: covidwho-2002118

ABSTRACT

BACKGROUND: Screening and intervention in pre-frailty can help prevent or delay frailty among older adults. Being overweight has shown associated with pre-frailty, and overweight is highly prevalent among community-dwelling older adults during COVID-19. However, the impact of visceral fat accumulation remains unclear. This study aimed to explore the association between visceral fat area and pre-frailty in community-dwelling older adults. METHODS: The participants of this study included community-dwelling older adults from three elderly welfare centers. The frailty phenotype was assessed using the frailty screening index. The body composition was measured using bioelectrical impedance analysis. RESULTS: A total of 214 community-dwelling older adults completed the questionnaire and measurements. After excluding 16 frail participants, 149 (75.3%) were pre-frailty. The mean age of participants was 75.4 ± 5.4 years, and 69.7% (138) of participants were women. There were 54 (27.3%) participants with high visceral fat area. The multivariable model showed that participants with high visceral fat area were at increased risk for pre-frailty (adjusted OR, 3.15; 95% CI, 1.26 - 7.87; P = 0.014), even after adjusted for age, sex, health status, and impact of COVID-19 pandemic. CONCLUSIONS: This study suggests that the association between visceral fat accumulation and pre-frailty may help to identify a new target for prevention. Further longitudinal studies are needed to determine their mechanisms in older adults.


Subject(s)
COVID-19 , Frailty , Aged , COVID-19/epidemiology , Cross-Sectional Studies , Female , Frail Elderly , Frailty/diagnosis , Frailty/epidemiology , Geriatric Assessment , Humans , Independent Living , Intra-Abdominal Fat , Japan/epidemiology , Male , Overweight , Pandemics
4.
PLoS One ; 17(7): e0272059, 2022.
Article in English | MEDLINE | ID: covidwho-1963044

ABSTRACT

BACKGROUND: Several studies have reported that obesity is associated with influenza infection; however, the role of visceral fat remains unclear. The aim of this study was to investigate the association between visceral fat and influenza infection in community-dwelling Japanese adults. METHODS: A cross-sectional study was performed using data from an annual community-based health check-up conducted from May to June in 2019. In total, 1,040 Japanese adults aged 20-89 years were enrolled in this study. Influenza infection status was determined by participants' responses to a self-administered questionnaire. The visceral fat area (VFA) was measured using a bioimpedance-type visceral fat meter. Participants were classified into four groups using the following cut-off points: VFA < 100 cm2 was set as the reference category according to the Japanese criteria, 100 ≤ VFA < 150 cm2, 150 ≤ VFA < 200 cm2, and 200 cm2 ≤ VFA. Logistic regression models were used to assess the association between VFA and influenza infection. RESULTS: In total, 119 participants had influenza infections in the past year. In the multivariate adjusted model, a higher VFA was significantly associated with increased influenza infection; the adjusted odds ratio for 200 cm2 ≤ VFA was 5.03 [95% confidence interval (CI): 1.07-23.6], that for 150 ≤ VFA < 200 cm2 was 1.97 (95% CI: 0.71-5.45), and that for 100 ≤ VFA < 150 cm2 was 1.62 (95% CI: 0.84-3.12), compared with that for VFA < 100 cm2 (p for trend = 0.049). These findings were confirmed in the same cohort the following year. CONCLUSIONS: Our results suggest that visceral fat accumulation is associated with influenza infection. Large-scale prospective studies using diagnostic information for influenza infection are required to confirm this association.


Subject(s)
Influenza, Human , Intra-Abdominal Fat , Adult , Cross-Sectional Studies , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Japan/epidemiology , Prospective Studies , Risk Factors
5.
Bol. malariol. salud ambient ; 62(1): 32-38, jun, 2022. tab, ilus
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-1772273

ABSTRACT

Hay dos tipos principales de tejido adiposo; el subcutáneo, que es menos activo metabólicamente, y el tejido adiposo visceral, que secreta constantemente citocinas inflamatorias y está relacionado a enfermedades metabólicas y cardiovasculares. Nuestro objetivo fue identificar la asociación entre el exceso de grasa visceral y la severidad de enfermedad en pacientes con COVID-19. Se realizó un estudio observacional analítico que incluyó a pacientes con COVID-19 admitidos al Hospital Carrión de Huancayo, Perú. Se utilizó la balanza de bioimpedancia para cuantificar la composición corporal, la variable dependiente fue la severidad de enfermedad. Se utilizó el análisis de regresión logística para determinar la asociación de la grasa visceral y otros parámetros antropométricos con severidad de enfermedad. Se analizaron a 120 personas con COVID-19, la edad promedio fue 50 años, el sexo masculino fue 60%. De acuerdo a los valores de la composición corporal emitidos por el equipo de bioimpedancia: La grasa visceral > 15Kg (OR 7,31; p = 0,001); la grasa corporal total > 35% (OR 5,58; p = 0,009) y el exceso de peso > 20Kg (OR 6,96; p = 0,011) fueron los parámetros asociados a enfermedad severa por COVID-19. La relación positiva entre el perímetro abdominal y la cantidad de grasa visceral fue significativo (p = 0,01). En la composición corporal, el exceso de grasa visceral es el mayor parámetro asociado a enfermedad severa por COVID-19(AU)


There are two main types of adipose tissue; the subcutaneous, which is less metabolically active, and the visceral adipose tissue, which constantly secretes inflammatory cytokines and is related to metabolic and cardiovascular diseases. Our objetive was to identify the association between the excess of visceral fat and disease severity in COVID-19 patients. An analytical observational study was carried out which included patients with COVID-19 admitted to the Carrión Hospital in Huancayo, Peru. The bioimpedance balance was used to quantify the body composition; the dependent variable was the severity of the disease. A logistic regression analysis was used to determine the association of visceral fat and other anthropometric parameters with the severity of the disease. Out of 120 people with COVID-19 were analyzed, the average age was 50 years, the male sex was 60%. According to the body composition values issued by the bioimpedance team: Visceral fat> 15Kg (OR 7.31; p = 0.001); Total body fat> 35% (OR 5.58; p = 0.009) and excess weight> 20Kg (OR 6.96; p = 0.011) were the parameters associated with severe disease due to COVID-19. The positive relationship between abdominal circumference and the amount of visceral fat was significant (p = 0.01). In body composition, excess visceral fat is the main parameter associated with severe COVID-19 disease(AU)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Aged, 80 and over , Respiratory Distress Syndrome, Newborn/epidemiology , Intra-Abdominal Fat/physiopathology , COVID-19/physiopathology , COVID-19/epidemiology , Obesity/physiopathology , Peru/epidemiology , Severity of Illness Index , Body Mass Index , Logistic Models , Regression Analysis , Hospitals
6.
J Nutr ; 151(9): 2513-2521, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1758779

ABSTRACT

BACKGROUND: Although intake of Hass avocado has been cross-sectionally linked to lower abdominal obesity, knowledge of the effects of avocado consumption on abdominal adiposity and glycemic outcomes remains limited. OBJECTIVE: The effects of avocado consumption on abdominal adiposity, insulin resistance, oral-glucose-tolerance test (OGTT), and estimated ß-cell function were evaluated. METHODS: A total of 105 adults aged 25-45 y (61% female) with BMI ≥25 kg/m2 were randomly assigned to an intervention (N = 53) that received a daily meal with 1 fresh Hass avocado or a control (N = 52) that received an isocaloric meal with similar ingredients without avocado for 12 wk. DXA was used to assess the primary outcomes of abdominal adiposity [visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and the ratio of VAT to SAAT (VS Ratio)]. Fasted glucose and insulin were used to assess the primary outcomes of insulin resistance (HOMA-IR), and insulin sensitivity (Matsuda index) and ß-cell function (Insulinogenic index) were estimated using an OGTT. Changes between groups were compared using an ANCOVA. Secondary analyses were conducted based on sex. RESULTS: The control group exhibited a greater reduction in SAAT [-54.5 ± 155.8 g (control) compared with 17.4 ± 155.1 g (treatment), P = 0.017] and increase in VS Ratio [0.007 ± 0.047 (control) compared with -0.011 ± 0.044 (treatment), P = 0.024]. Among females, the treatment group exhibited a greater reduction in VAT [1.6 ± 89.8 g (control) compared with -32.9 ± 81.6 g (treatment), P = 0.021] and VS Ratio [0.01 ± 0.05 (control) compared with -0.01 ± 0.03 (treatment), P = 0.001]. Among males, there was no significant difference between groups in changes in abdominal adiposity or glycemic outcomes. CONCLUSIONS: Daily consumption of 1 fresh Hass avocado changed abdominal adiposity distribution among females but did not facilitate improvements in peripheral insulin sensitivity or ß-cell function among adults with overweight and obesity.This study was registered at clinicaltrials.gov as NCT02740439.


Subject(s)
Insulin Resistance , Persea , Adiposity , Body Mass Index , Female , Glucose Tolerance Test , Humans , Intra-Abdominal Fat , Male , Obesity , Obesity, Abdominal , Overweight
7.
Int J Obes (Lond) ; 46(5): 1009-1017, 2022 05.
Article in English | MEDLINE | ID: covidwho-1655531

ABSTRACT

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.


Subject(s)
COVID-19 , Embolism, Fat , COVID-19/complications , COVID-19 Testing , Endothelial Cells/metabolism , Humans , Hyalin/metabolism , Inflammation/metabolism , Intra-Abdominal Fat/metabolism , Lipids , Lung , Obesity/metabolism , SARS-CoV-2
8.
Mol Cell Biochem ; 477(4): 1155-1193, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1653634

ABSTRACT

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.


Subject(s)
Adiposity/physiology , Body Mass Index , COVID-19/physiopathology , Intra-Abdominal Fat/physiology , Obesity/physiopathology , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Humans , Inflammation/physiopathology , Pandemics , Risk Factors , SARS-CoV-2/physiology
9.
BMC Infect Dis ; 21(1): 1240, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1566511

ABSTRACT

BACKGROUND: Clarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19. METHODS: The present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed. RESULTS: A total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008-1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000-1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference). CONCLUSIONS: A higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.


Subject(s)
COVID-19 , Intra-Abdominal Fat , Body Mass Index , Cohort Studies , Humans , Intra-Abdominal Fat/diagnostic imaging , Prognosis , SARS-CoV-2
10.
Dig Dis Sci ; 67(9): 4484-4491, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1530342

ABSTRACT

BACKGROUND: Patients with SARS-CoV-2 who present with gastrointestinal symptoms have a milder clinical course than those who do not. Risk factors for severe COVID-19 disease include increased adiposity and sarcopenia. AIMS: To determine whether body composition risk factors are associated with worse outcomes among patients with gastrointestinal symptoms. METHODS: This was a retrospective study of hospitalized patients with COVID-19 who underwent abdominal CT scan for clinical indications. Abdominal body composition measures including skeletal muscle index (SMI), intramuscular adipose tissue index (IMATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and liver and spleen attenuation were collected. The association between body composition measurements and 30-day mortality was evaluated in patients with and without gastrointestinal symptoms at the time of positive SARS-CoV-2 test. RESULTS: Abdominal CT scans of 190 patients with COVID-19 were evaluated. Gastrointestinal symptoms including nausea, vomiting, diarrhea, or abdominal pain were present in 117 (62%). Among patients without gastrointestinal symptoms, those who died had greater IMATI (p = 0.049), less SMI (p = 0.010), and a trend toward a greater VAT/SAT ratio. Among patients with gastrointestinal symptoms, those who died had significantly greater IMATI (p = 0.025) but no differences in other measures. CONCLUSIONS: Among patients with COVID-19, those without gastrointestinal symptoms showed the expected associations between mortality and low SMI, high IMATI, and trend toward higher VAT/SAT ratio, but those with gastrointestinal symptoms did not. Future studies should explore the mechanisms for the altered disease course in patients with COVID-19 who present with gastrointestinal symptoms.


Subject(s)
COVID-19 , Body Composition , Body Mass Index , Humans , Intra-Abdominal Fat , Retrospective Studies , SARS-CoV-2
11.
Eur J Radiol ; 145: 110031, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1527655

ABSTRACT

PURPOSE: To assess prognostic value of body composition parameters measured at CT to predict risk of hospitalization in patients with COVID-19 infection. METHODS: 177 patients with SARS-CoV-2 infection and with abdominopelvic CT were included in this retrospective IRB approved two-institution study. Patients were stratified based on disease severity as outpatients (no hospital admission) and patients who were hospitalized (inpatients). Two readers blinded to the clinical outcome segmented axial CT images at the L3 vertebral body level for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), muscle adipose tissue (MAT), muscle mass (MM). VAT to total adipose tissue ratio (VAT/TAT), MAT/MM ratio, and muscle index (MI) at L3 were computed. These measures, along with detailed clinical risk factors, were compared in patients stratified by severity. Various logistic regression clinical and clinical + imaging models were compared to discriminate inpatients from outpatients. RESULTS: There were 76 outpatients (43%) and 101 inpatients. Male gender (p = 0.013), age (p = 0.0003), hypertension (p = 0.0003), diabetes (p = 0.0001), history of cardiac disease (p = 0.007), VAT/TAT (p < 0.0001), and MAT/MM (p < 0.0001), but not BMI, were associated with hospitalization. A clinical model (age, gender, BMI) had AUC of 0.70. Addition of VAT/TAT to the clinical model improved the AUC to 0.73. Optimal model that included gender, BMI, race (Black), MI, VAT/TAT, as well as interaction between gender and VAT/TAT and gender and MAT/MM demonstrated the highest AUC of 0.83. CONCLUSION: MAT/MM and VAT/TAT provides important prognostic information in predicting patients with COVID-19 who are likely to require hospitalization.


Subject(s)
COVID-19 , Body Composition , Body Mass Index , Hospitalization , Humans , Intra-Abdominal Fat , Male , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
12.
Eur J Clin Invest ; 52(2): e13685, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1440744

ABSTRACT

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.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Intra-Abdominal Fat/metabolism , Leukocytes, Mononuclear/metabolism , Obesity/genetics , Receptors, Coronavirus/genetics , Subcutaneous Fat/metabolism , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Bariatric Surgery , COVID-19 , DNA Methylation , Diet, Ketogenic , Diet, Reducing , Female , Gene Expression Regulation , Humans , Male , Middle Aged , Obesity/metabolism , Obesity/therapy , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Obesity, Morbid/therapy , Receptors, Coronavirus/metabolism , SARS-CoV-2 , Weight Loss
13.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Article in English | MEDLINE | ID: covidwho-1394754

ABSTRACT

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.


Subject(s)
COVID-19/metabolism , Cardiomyopathies/metabolism , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Adipose Tissue/metabolism , Adipose Tissue/pathology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/immunology , Cardiomyopathies/immunology , Cardiomyopathies/pathology , Heart Diseases/immunology , Heart Diseases/metabolism , Heart Diseases/pathology , Humans , Inflammation , Intra-Abdominal Fat/pathology , Obesity/complications , Obesity/immunology , Obesity/pathology , Pericardium , Prognosis , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism
14.
Front Immunol ; 12: 702506, 2021.
Article in English | MEDLINE | ID: covidwho-1376698

ABSTRACT

Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing ß-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering ß-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop ß-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier in vitro and in vivo studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering ß-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.


Subject(s)
Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/virology , Intra-Abdominal Fat/immunology , Intra-Abdominal Fat/virology , Parvoviridae Infections/immunology , Animals , Humans , Parvovirus/immunology , Rats
15.
J Nutr ; 151(8): 2236-2244, 2021 08 07.
Article in English | MEDLINE | ID: covidwho-1280112

ABSTRACT

BACKGROUND: COVID-19 has been associated with cases of severe respiratory illness, admissions to intensive therapy units (ITUs), and high mortality rates. OBJECTIVES: The aim of the present study was to examine the relation between computed tomography- body composition (CT-BC) measurements, systemic inflammation, and clinical outcomes in those with COVID-19. METHODS: Patients who presented to our institution between March 17 and May 1, 2020, with a positive PCR test for COVID-19 or characteristic radiological changes, were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, poGPS, NLR , CT-BC measurements, and clinical outcomes including ITU admission and 30-d mortality, of those admitted. RESULTS: Sixty-three patients met the study inclusion criteria. Forty-two patients (67%) were aged ≥70 y, 30 (47.6%) were male and 34.9% ( n = 22) had a poGPS ≥1. ITU admission was significantly associated with a high VFA ( P < 0.05). Thirty-day mortality was associated with high VFA (P < 0.05) and low SMI (P < 0.05). CONCLUSIONS: Sarcopenia in the presence of obesity was associated with clinical outcomes including greater 30-d mortality.


Subject(s)
Body Composition , COVID-19/mortality , Inflammation/etiology , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Body Mass Index , COVID-19/metabolism , COVID-19/pathology , Female , Hospitalization , Hospitals, Teaching , Humans , Intra-Abdominal Fat , Male , Middle Aged , Sarcopenia/etiology
16.
Nutr Metab Cardiovasc Dis ; 31(7): 2156-2164, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1249046

ABSTRACT

BACKGROUND AND AIMS: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. METHODS AND RESULTS: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). CONCLUSION: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. TRIAL REGISTRATION: NCT04318366.


Subject(s)
Adiposity , COVID-19/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , Obesity/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed , Aged , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Female , Hospital Mortality , Humans , Intra-Abdominal Fat/physiopathology , Italy , Male , Middle Aged , Obesity/mortality , Obesity/physiopathology , Pericardium , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors
17.
Obesity (Silver Spring) ; 29(9): 1427-1433, 2021 09.
Article in English | MEDLINE | ID: covidwho-1239993

ABSTRACT

OBJECTIVE: Adipose tissue plays a role in the novel coronavirus disease 2019 (COVID-19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with a high degree of inflammation in severe COVID-19. Whether and how adipose tissue may respond to the COVID-19 therapies is unknown. METHODS: The difference in computed tomography-measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), was retrospectively analyzed in 72 patients (mean [SD] age was 59.6 [12.4] years, 50 patients [69%] were men) at the hospital admission for COVID-19 and 99 days (interquartile range = 71-129) after discharge. RESULTS: At the admission, EAT-HU was significantly correlated with blood glucose levels, interleukin 6, troponin T levels, and waist circumference. EAT-HU decreased from -87.21 (16.18) to -100.0 (11) (p < 0.001), whereas SAT-HU did not change (-110.21 [12.1] to -111.11 [27.82]; p = 0.78) after therapy. Changes in EAT-HU (expressed as ∆) significantly correlated with dexamethasone therapy (r = -0.46, p = 0.006) and when dexamethasone was combined with tocilizumab (r = -0.24, p = 0.04). CONCLUSIONS: Dexamethasone therapy was associated with significant reduction of EAT inflammation in COVID-19 patients, whereas SAT showed no changes. Anti-inflammatory therapies targeting visceral fat may be helpful in COVID-19.


Subject(s)
COVID-19 , Dexamethasone/therapeutic use , Intra-Abdominal Fat , Pericardium , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Female , Humans , Inflammation , Intra-Abdominal Fat/diagnostic imaging , Male , Middle Aged , Pericardium/diagnostic imaging , Retrospective Studies
18.
PLoS One ; 16(5): e0251768, 2021.
Article in English | MEDLINE | ID: covidwho-1229049

ABSTRACT

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.


Subject(s)
Body Composition , COVID-19/diagnostic imaging , COVID-19/mortality , Intra-Abdominal Fat/diagnostic imaging , Mass Chest X-Ray/methods , SARS-CoV-2/genetics , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Body Mass Index , COVID-19/epidemiology , COVID-19/virology , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , Risk Factors , Treatment Outcome
19.
Clin Nutr ESPEN ; 43: 163-168, 2021 06.
Article in English | MEDLINE | ID: covidwho-1174154

ABSTRACT

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.


Subject(s)
Body Mass Index , COVID-19/metabolism , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Severity of Illness Index , Subcutaneous Fat/metabolism , Adiposity , Aged , COVID-19/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Obesity/complications , Obesity/epidemiology , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Obesity, Abdominal/metabolism , SARS-CoV-2
20.
J Prim Care Community Health ; 12: 2150132721996283, 2021.
Article in English | MEDLINE | ID: covidwho-1112423

ABSTRACT

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.


Subject(s)
Body Mass Index , COVID-19 , Obesity/therapy , Severity of Illness Index , Awareness , COVID-19/etiology , COVID-19/mortality , COVID-19/prevention & control , Hospital Mortality , Hospitalization , Humans , Insulin Resistance , Intensive Care Units , Intra-Abdominal Fat/metabolism , Obesity/complications , Obesity/metabolism , Odds Ratio , Respiration, Artificial , Risk Factors , SARS-CoV-2
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