PERICARDIAL INVOLVEMENT ASSOCIATED WITH SARS-COV-2 INFECTION. PROSPECTIVE OBSERVATION IN THE COVID- WARD.

Purpose. To identify the occurrence and structure of changes in the pericardium ultrasonography among patients who have undergone COVID-19 and have cardiological symptoms, as well as to compare these changes with the pericarditis aspects and the infection time duration in a prospective cohort observational study. Methods. Inclusion/exclusion criteria: current or transferred COVID-19, new symptoms that occurred during or after infection and forced to consult a cardiologist, the absence of other prerequisites for pericarditis and vaccination against SARS-CoV-2. Echocardiography was performed with an emphasis on the pericardium and an assessment of the echogenicity amplification, the area of the hyperechoic zone, thickness and artifacts, as well as a questionnaire. Results. From 05.2020 to On 10.2020, 335 patients from the covid ward and 284 patients from the out-patient clinic were included. 86% of patients had transient chest discomfort. The peaks of treatment accrued to 4-5 and 10-11 weeks (Me 10[2-36] (1 to 64) weeks) from SARS-CoV-2 infection occurred. Typical ECG changes were registered in 3%, pericardial friction noise - in 7% of patients. In 20% of patients discomfort in the heart area was the first, in 27% - the dominant, in 14% - the only symptom of COVID-19. According to EchoCG data, 96% of the examined patients had ultrasound signs of different changes in the pericardium: slight effusion in 65%, signs of tamponade in 2%, thickening in 12%, local hyperechogenicity in 83%, local adhesion in 8% of patients. The group without pericardial changes was distinguished by the presence of epicardial fat >7 mm. A combination of the echo-cardiography criteria with the second symptom recorded at the visit or earlier was present in 76% of the applicants. Comparison of the recorded ultrasound patterns with the time elapsed since infection allowed us to distinguish ultrasound phases: 1) the phase of damage (pattern of initial edema) occurred at 1 week, 2) the phase of edema /exudation (pattern of visible effusion) - at 3 weeks, 3) fibrosis (pattern of pericardial compaction) - at 11 weeks, 4) regression of inflammatory changes (pattern of local fibrin deposition) - on week 22, 5) residual signs of transferred inflammation may be visualized in patients with symptoms 44 weeks after COVID-19. Conclusions. Consideration of the infectious process triggered by SARS-CoV-2, as a systemic inflammation, allows us to interpret the phenomenon of pericardial involvement as a reactive serositis having ultrasound phases. It was possible to trace some patterns of echocardiography at different stages of the infectious and post-infectious period. Clinical data of 76% of patients can be interpreted as pericarditis, changes in 20% - as an increase in echogenicity of the pericardium.Copyright © 2022 Russian Electronic Journal of Radiology. All rights reserved.

Comparison of Thorax Computed Tomography Based Body Composition Parameters Between COVID-19 Positive and Negative Patients: A Cross-Sectional Study

Objective: To compare body fat-muscle and visceral obesity indices that can be measured with thorax computed tomography (CT) between reverse transcriptase-polymerase chain reaction (RT-PCR) positive and negative patients. Material(s) and Method(s): This ret-rospective, comparative study included 141 PCR (+) and 150 PCR (-) patients who applied to our hospital with flu-like symptoms without having the comorbid diseases and undergone thoracic CT between April 1, 2020-July 1, 2020. For the each patient, the ratio of thoracic subcutaneous adipose tissue thickness to pectoralis major muscle thickness (TSAT/PMJ), epicardial adipose tissue thickness (EAT), liver density (LD), abdominal subcutaneous adipose tissue thickness to psoas major muscle thickness ratio (ASAT/ PSM), subcutaneous abdominal adipose tissue thickness to erector spinae muscle thickness ratio (ASAT/ESM) was measured. The comparison was made between the subgroups in terms of age, gender, and measured parameters. Result(s): Statistically significant difference was found between PCR (+) and (-) individuals in terms of EAT mean (p<0.05). TSAT/PMJ, ASAT/PSM and ASAT/ESM ratios were higher in women (p <0.05). The mean EAT in men was increased in the PCR (+) group (p<0.05). In PCR (+) group, LD decreased, EAT increased with increasing age (p<0.05). PCR (+) and PCR (-) groups didn't show significant difference (p>0.05) in terms of TSAT/PMJ, ASAT/PSM, LD, ASAT/ESM. Conclusion(s): Higher EAT values can increase the risk of getting coronavirus disease-2019 (COVID-19) infection. Peripheral fat-muscle indices don't increase the risk of contracting COVID-19 infection.Copyright © 2023 by Turkiye Klinikleri.

Epicardial Fat Necrosis After COVID-19 Infection: A Case Report.

Epipericardial or epicardial fat necrosis (EFN) is a self-limited inflammatory process occurring in the mediastinal fat surrounding the heart. It is an uncommon cause of acute chest pain and mimics more critical clinical disorders such as acute coronary syndrome, aortic dissection, and pulmonary embolism. However, EFN is frequently overlooked and under-recognized in emergency departments (EDs) owing to the unfamiliarity of this condition among physicians and radiologists. Herein, we present the case of a previously healthy young male patient, with a recent history of mild COVID-19 infection (two weeks before presentation), who presented to the ED for acute chest pain. Paraclinical evaluation including computed tomography (CT) of the chest revealed fat stranding along with the left epicardial fat pad in favor of EFN.

MACROPHAGES IN EPICARDIAL ADIPOSE TISSUE AND SERUM NT-proBNP IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Coronary artery disease (CAD) is widely considered a chronic inflammatory disorder, and dysfunction of epicardial adipose tissue could be an important source of the inflammation. Amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a known marker of cardiovascular disorders of cardiac origin. Recent studies show that inflammatory stimuli may influence its secretion. Our purpose was to evaluate NT-proBNP serum concentration in relation to immune cell ratios in epicardial adipose tissue (EAT), and cytokine levels in the patients with stable CAD. Patients with stable CAD and heart failure classified into classes II-III, according to the New York Heart Association (NYHA) scale, scheduled for the coronary artery bypass graft (CABG) surgery, were recruited into the study (n = 10;59.5 (53.0-65.0) y. o.;50% males). The EAT and subcutaneous adipose tissue (SAT) specimens were harvested in the course of CABG surgery. Immunostaining with anti-CD68, anti-CD45, anti-IL-1β and anti-TNFα monoclonal antibodies was performed to evaluate cell composition by differential counts per ten fields (400 magnification). Fasting venous blood was obtained from patients before CABG. Blood was centrifuged at 1500g, aliquots were collected and stored frozen at -40 °С until final analysis. Concentrations of NT-proBNP, IL-1β, IL-6, IL-10, TNFα were determined in serum samples by enzyme-linked immunosorbent assay (ELISA). We have found increased production of IL-1β and TNFα cytokines in EAT compared to SAT. Concentrations of NT-proBNP exceeded 125 pg/ml in 4 patients, and correlations between the CD68+ macrophage counts in both EAT and SAT samples (rs = 0.762;p = 0.010 and rs = 0.835;p = 0.003, respectively). NT-proBNP levels showed positive relations with CD45+ leukocyte counts (rs = 0.799;p = 0.006), and with IL-1β+ cell numbers (rs = 0.705;p = 0.023) in EAT samples only. As for the serum biomarkers, NT-proBNP levels showed negative correlation with fasting glucose levels (rs = -0.684;p = 0.029), and positive correlation with serum IL-6 concentrations (rs = 0.891;p = 0.001). Increased serum concentrations of NT-proBNP in CAD patients correlate with accumulation of macrophages in EAT, which is associated with increased production of IL-1β in EAT and correlates with some metabolic parameters.

May Hepatic Steatosis Be Associated with Gynecomastia and Epicardial Fat? A Retrospective Study of 599 Male Patients

Objective: There is no study in the literature investigating the association of hepatic steatosis both gynecomastia and epicardial fat thickness together. We determined the correlations between hepatic steatosis through liver density, gynecomastia and epicardial fat thickness in patients undergoing computed tomography (CT) scans due to suspected coronavirus disease-2019 (COVID-19) symptoms. Methods: A total of 599 male patients who underwent chest CT scans because of a presumed diagnosis of COVID-19 in our radiology clinic were included in the study. Patients’ age, diameters of the subareolar glandular tissues of the right and left breasts, the right retroareolar fatty tissue, liver and spleen density, epicardial fat thickness and biochemical parameters were recorded and analyzed. Laboratory analyses were performed according to the standard methods. Results: The mean age of the patients was 47.21±15.00 years. The left subareolar tissue thickness and the right retroareolar fatty tissue thickness that are used to indicate gynecomastia were significantly correlated with liver density in the negative direction (r=-0.137, p<0.001;r=-0.172, p<0.001;respectively). Epicardial fat thickness was statistically significantly correlated with right subareolar tissue thickness (r=0.085, p=0.037), left subareolar tissue thickness (r=0.101, p=0.014) and right retroareolar fatty tissue thickness (r=0.148, p<0.001). Conclusion: The results of this study showed that gynecomastia was significantly correlated with both age and hepatic steatosis. Epicardial fat thickness is also associated with hepatic steatosis. We demonstrated the significant correlations between epicardial fat thickness and gynecomastia for the first time. Nevertheless, our results need to be confirmed by further comprehensive studies.

Epicardial adiposity as a predictor of COVID-19 severity in overweight and obese patients

Aim. To evaluate epicardial adiposity (EA), verified on the basis of epicardial adipose tissue (EAT) thickness according to echocardiography, as a possible predictor of the severity of coronavirus disease 2019 (COVID-19) course in overweight and obese patients in a retrospective analysis of data. Material and methods. We analyzed data on 165 patients (age, 45,2±4,7 years;men, 67,9%;body mass index, 31,4±3,5 kg/m2) who received outpatient or inpatient treatment for symptomatic COVID-19 in period from March 2020 to November 2021. Patients with diabetes, stage III-V chronic kidney disease and/or cardiovascular disease were excluded from the analysis, with the exception of hypertension. EA was verified in the case of EAT thickness ≥4,8 mm for persons aged 35-45 years and ≥5,8 mm for persons 46-55 years old. Results. Patients with EA were characterized by higher hospitalization rates (52,2% vs 9,0%, p<0,01), moderate (56,5% vs 19,7%, p<0,01), high and very high severity (17,4% vs 3,3%, p<0,01) of disease course, lung injury of CT-1, CT-2 and CT-3 (32,6% vs 9,8% (p<0,01), 21,7% vs 7,4% (p<0,05), and 15,2% vs 2,5% (p<0,01), respectively), invasive ventilation (8,7% vs 0,8%, p<0,05) and C-reactive protein >10 mg/l (69,6% vs 21,3%, p<0,01). Predictors of hospitalization for symptomatic COVID-19 according to multivariate logistic regression analysis were age, fasting glycemia, systolic blood pressure, EAT thickness, which was characterized by the highest standardized regression coefficient among other predictors (0,384, p<0,001). Conclusion. EAT thickness may be one of the predictors of COVID-19 severity in overweight and obese patients. Persons with EA in the case of COVID-19 need more careful monitoring and measures to prevent severe course and complications.

The predictive value of epicardial fat volume for clinical severity of COVID-19.

Introduction: Epicardial adipose tissue serves as a source of inflammatory cytokines and mediators. Cytokine storm is an important cause of morbidity and mortality in coronavirus disease 2019 (COVID-19). Objectives: To investigate the association between epicardial fat volume (EFV), inflammatory biomarkers and clinical severity of COVID-19. Methods: This retrospective study included 101 patients who were infected with COVID-19. Serum inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and ferritin levels were measured. Computed tomography images were analyzed and semi-automated measurements for EFV were obtained. The primary composite endpoint was admission to the intensive care unit (ICU) or death. Results: The primary composite endpoint occurred in 25.1% (n=26) of patients (mean age 64.8±14.8 years, 14 male). A total of 10 patients died. EFV, CRP, PCT, ferritin and IL-6 levels were significantly higher in ICU patients. Moreover, a positive correlation was determined between EFV and CRP (r: 0.494, p<0.001), PCT (r: 0.287, p=0.005), ferritin (r: 0.265, p=0.01) and IL-6 (r: 0.311, p=0.005). On receiver operating characteristic analysis, patients with EFV >102 cm3 were more likely to have severe complications. In multivariate logistic regression analysis, EFV independently predicted admission to the ICU at a significant level (OR: 1.02, 95% CI: 1.01-1.03, p=0.025). Conclusion: EFV and serum CRP, IL-6, PCT and ferritin levels can effectively assess disease severity and predict the outcome in patients with COVID-19. EFV is an independent predictor of admission to the ICU in hospitalized COVID-19 patients.

Introdução: O tecido adiposo epicárdico é fonte de citocinas inflamatórias e mediadores. A tempestade de citocinas é uma importante causa de morbilidade e mortalidade na doença coronavírus 2019 (COVID-19). Objetivos: Investigar a associação entre volume adiposo epicárdico (VAE), biomarcadores inflamatórios e gravidade clínica da COVID-19. Métodos: Este estudo retrospetivo incluiu 101 doentes infetados com COVID-19. Foram avaliados biomarcadores inflamatórios séricos, incluindo os níveis de proteína C-reativa (PCR), de interleucina-6 (IL-6), de procalcitonina (PCT) e de ferritina. Foram analisadas imagens de tomografia computorizada (TC) e foram obtidas medições semi-automáticas do VAE. O endpoint primário composto foi a admissão na unidade de cuidados intensivos (UCI) ou morte. Resultados: O endpoint primário ocorreu em 25,1% (n=26) dos doentes (idade média 64,8±14,8 anos, 14 homens). Um total de 10 doentes morreu. Os níveis de VAE, PCR, PCT, ferritina e IL-6 foram significativamente superiores nos doentes internados na UCI. Além disso, verificou-se uma correlação positiva entre o VAE e a PCR (r: 0,494, p<0,001), PCT (r: 0,287, p=0,005), ferritina (r: 0,265, p=0,01) e IL-6 (r: 0,311, p=0,005). Na análise de regressão logistica multivariada, os doentes com VAE>102 cm3 tinham maior probabilidade de ter complicações graves. Conclusão: O VAE e os níveis séricos de PCR, IL-6, PCT e ferritina podem avaliar a gravidade da doença e prever o resultado em doentes com COVID-19. O VAE constitui um fator preditivo na admissão dos doentes hospitalizados com COVID-19 numa UCI.

Epicardial adipose tissue thickness in COVID-19 hospitalized patients: a tool for risk stratification

Background: Coronavirus Disease 2019 (COVID-19) impacted public health systems, overwhelming the intensive care units(ICU)(1).Epicardial adipose tissue (EAT) thickness is a potential novel parameter, which can be assessed using standard computer tomography(CT) for the prediction of worse prognosis in COVID-19(2,3). Purpose: We aimed to investigate the association of right ventricle (RV)-EAT thickness with the need for invasive mechanical ventilation, vasopressor support or ICU admission and in-hospital mortality in COVID-19. Methods: We analyzed 310 consecutive hospitalized patients with confirmed COVID-19 by RT-PCR, between March and April 2020.EAT thickness was assessed during the acute setting of the disease using low dose non-contrast chest CT.Maximal EAT thickness was determined on axial image series at the level of the RV free wall perpendicular to the surface of the heart(Figure 1).Intra-and interobserver reproducibility for the RV-EAT thickness measurement was assessed in 20 random patients after two weeks, by the primary and a second investigator. Data included demographics, clinical evaluation, comorbidities, treatment and complications.Peak lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) were defined as the highest level during hospitalization.The primary combined endpoint was ICU admission, invasive mechanical ventilation and vasopressor therapy.The secondary outcome was in-hospital mortality. Results: Median age was 64 years (interquartile range:53 to 79 years,58.1% males).106(34.2%) patients reached the primary endpoint.Inhospital mortality rate was 19.5% (59 patients).Among patients with combined endpoint, the mortality rate was 35.8% (38 patients).RV-EAT thickness was higher in patients with combined endpoint (5.0 ±2.6 mm versus 4.3 ± 2.2 mm, p = 0.021).Additionally, patients with the composite endpoint had more diabetes mellitus (p = 0.028) and history of coronary artery disease (p = 0.020).Multivariable analysis showed that RV-EAT thickness predicted the primary endpoint, irrespective of risk factors and disease severity (p = 0.014, OR 1.157,95%CI 1.030-1.300;p = 0.031, OR 1.146,95%CI 1.013-1.298, respectively)(Figure 2).Moreover, peak CRP and peak LDH were associated with both endpoints( Figure 2).However, RV-EAT thickness was not predictive for mortality (p = 0.561, OR 1.039, 95%CI 0.913-1.183). Intraobserver and interobserver reproducibility were good:0.88 (95%CI 0.66-0.95) and 0.86 (95%CI 0.65-0.94). Conclusion: RV-EAT thickness, easily and rapidly assessed by standard low dose non-contrast chest CT was associated with higher incidence of ICU admission, need for mechanical ventilation and vasopressor support in hospitalized COVID-19 patients.Although no independent association between RV-EAT and in-hospital mortality was found, RV-EAT thickness may serve as surrogate marker of severity, before the rise of inflammatory biomarkers and may reflect inflammation changes within the myocardium in COVID-19.

Early Cardiac Marker of Mortality in COVID-19

Background. Epicardial adipose tissue (EAT) is a highly inflammatory depot of fat, with high concentrations of IL-6 and macrophages, which can directly reach the myo-pericardium via the vasa vasorum or paracrine pathways. TNF-α and IL-6 diminish cardiac inotropic function, making EAT inflammation a potential cause of cardiac dysfunction. Methods. A retrospective cohort study assessing EAT Thickness and Density from CT scans, without contrast, from adult patients during index admission for COVID-19 infection at Mount Sinai Medical Center from March 2020 to January 2021. A total of 1,644 patients were screened, of which 148 patients were included. Follow-up completed until death or discharge. The descriptive analysis was applied to the general population, parametric test of normality for comparisons between groups. Kaplan survival analysis was conducted after survival distribution was confirmed significant. It was followed by the assumption of normality by Q-Q Plot, prior to performing a multiple regression analysis in the vulnerable group using a K-Matrix input for cofounders. A log-rank test was conducted to determine differences in the survival distributions for the different ranges of EAT thickness. Results. A total of 148 Participants were assigned to two groups based on epicardial adipose tissue in order to classify them as increased or decreased risk of cardiovascular risk: >5mm (n = 99), < 5mm (n = 49). The survival percentage was higher in the group with no EAT inflammation compared to the group with EAT inflammation (95.0% and 65%, respectively). Participants with EAT >5mm had a median day of hospital stay of 18 (95% CI, 16.86 to 29.92). The survival distributions for the two categories were statistically significantly different, χ2(2) = 6.9, p < 0.01. A Bonferroni correction was made with statistical significance accepted at the p < 0.025 level. There was a statistically significant difference in survival distributions for the EAT >5 mm vs EAT < 5 mm, χ2(1) =6.953, p = 0.008. Conclusion. There was an association with increased EAT thickness and increased mortality. These findings suggest that EAT thickness can be used as a prognostic factor and as a risk factor for increased mortality in patients with COVID-19.

Epicardial adipose tissue thickness as a mortality risk marker in covid-19

Intro: Cardiac involvement in COVID-19 infection is common. Epicardial adipose tissue functions as an inflammatory depot, and a thickness (EAT-T) >5mm is associated with increased cardiovascular risk. The present study assessed the significance of increased EAT-T in patients with COVID-19. Methods: A retrospective cohort study of 149 consecutive patients diagnosed with COVID-19 between March 2020 to January 2021 was performed. Inclusion criteria were lab-confirmed COVID19 infection and having a Chest CT scan without contrast during hospitalization. EAT-T was measure in right ventricle free wall (Figure 1). Characteristic of patients and comparisons were analyzed by T-Test and Chi-square. Log-linear analysis and cumulative logistic regression was carried out to predict effect between EAT-T and mortality Results: The mean age was 67 ± 15 years, 65% were male, and time from onset of symptoms was 7 ± 5 days. Forty-seven (31.5%) patients required mechanical ventilation, and 34 (22.8%) required vasopressors. Medical therapy included convalescent plasma (36%), Remdesivir (28%), Tocilizumab (46%), Enoxaparin (64%), and Dexamethasone (39%). There were 36 (24.2%) inhospital deaths, with a greater incidence amongst patients with an EAT-T > 5 mm versus ≤ 5 mm (95 vs 5%, p=.001). Notably, age was not significantly different on patients with in-hospital mortality (69 vs 66 years, p=0.5), and higher EAT-T by 2.17 mm on patient with acute respiratory distress syndrome (p=.001) and 10.9 mm in myocardial infarction (p=.02). In multivariable analysis an EAT-T >5mm was associated with an increased risk of mortality (OR 12.3, 95% CI 3-55, p=.001). In the presence of EAT-T > 5 mm, no effect was observed by chronic kidney disease, hypertension, coronary artery disease, dyslipidemia, or body mass index (p >0.5). Conclusions: In patients with COVID-19, an EAT-T > 5 mm is associated with increased risk of inhospital mortality and may provide important risk stratification.

Rapid prognostic stratification using Point of Care ultrasound in critically ill COVID patients: The role of epicardial fat thickness, myocardial injury and age.

PURPOSE: The burden of critical COVID-19 patients in intensive care units (ICU) demands new tools to stratify patient risk. We aimed to investigate the role of cardiac and lung ultrasound, together with clinical variables, to propose a simple score to help predict short-term mortality in these patients. MATERIAL AND METHODS: We collected clinical and laboratorial data, and a point-of-care cardiac and lung ultrasound was performed in the first 36 h of admission in the ICU. RESULTS: Out of 78 patients (61 ± 12y-o, 55% male), 33 (42%) died during the hospitalization. Deceased patients were generally older, had worse values for SOFA score, baseline troponin levels, left ventricular ejection fraction (LVEF), LV diastolic function, and increased epicardial fat thickness (EFT), despite a similar prevalence of severe lung ultrasound scores. Based on the multivariable model, we created the POCOVID score, including age (>60 years), myocardial injury (LVEF<50% and/or usTnI>99til), and increased EFT (>0.8 cm). The presence of two out of these three criteria identified patients with almost twice the risk of death. CONCLUSIONS: A higher POCOVID score at ICU admission can be helpful to stratify critical COVID-19 patients with increased in-hospital mortality and to optimize medical resources allocation in more strict-resource settings.

Epicardial adipose tissue and severe Coronavirus Disease 19.

BACKGROUND: Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with Coronavirus Disease 19 (COVID-19) severity. We aimed to investigate whether an association also exists for EAT. MATERIAL AND METHODS: We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 [Formula: see text] 6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity. RESULTS: We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters. CONCLUSIONS: Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.

Dual role for angiotensin-converting enzyme 2 in Severe Acute Respiratory Syndrome Coronavirus 2 infection and cardiac fat.

Angiotensin-converting enzyme 2 (ACE2) has been an increasingly prevalent target for investigation since its discovery 20 years ago. The finding that it serves a counterregulatory function within the traditional renin-angiotensin system, implicating it in cardiometabolic health, has increased its clinical relevance. Focus on ACE2's role in cardiometabolic health has largely centered on its apparent functions in the context of obesity. Interest in ACE2 has become even greater with the discovery that it serves as the cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), opening up numerous mechanisms for deleterious effects of infection. The proliferation of ACE2 within the literature coupled with its dual role in SARS-CoV-2 infection and obesity necessitates review of the current understanding of ACE2's physiological, pathophysiological, and potential therapeutic functions. This review highlights the roles of ACE2 in cardiac dysfunction and obesity, with focus on epicardial adipose tissue, to reconcile the data in the context of SARS-CoV-2 infection.

Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer.

AIMS: Obesity, diabetes and cardiovascular disease are associated with COVID-19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. MATERIALS AND METHODS: Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open-heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA. RESULTS: Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u., P = .05 for ACE2 and 1.68 [1.66-1.78] vs 1.66 [1.63-1.69] a.u., P < .05 for ADAM17). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels (P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55-1.63] vs 1 [1-1.34]), were not correlated with the soluble ACE2. CONCLUSION: Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS-CoV-2 infection.