Do adipocytes serve as a reservoir for severe acute respiratory symptom coronavirus-2?

Obesity is associated with a higher risk of severe coronavirus disease 2019 (COVID-19) and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate severe acute respiratory symptom coronavirus-2 (SARS-CoV-2) cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight, and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In the adipose tissue from patients who died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than 3 weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.

The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial.

PURPOSE: Metabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS. METHODS: This parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%-45% carbohydrates and 35%-40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%-55% carbohydrates and 25%-30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention. FINDINGS: Compared with the NWLD group, following an MRCD significantly decreased weight (-4.82 vs -2.40 kg; P = 0.01), body mass index (-1.88 vs -0.94 kg/m2; P = 0.01), waist circumference (-5.34 vs -2.75 cm; P = 0.01), hip circumference (-2.58 vs -1.11 cm; P = 0.01), serum triglyceride (-26.8 vs -7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance. IMPLICATIONS: Moderate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1.

Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study.

BACKGROUND: To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment. METHODS: From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes. RESULTS: Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%. CONCLUSION: The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study. / Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte.

BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. OBJECTIVE: We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. METHODS: This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. RESULTS: Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI -0.217 to -0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). CONCLUSION: Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

FUNDAMENTO: Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. OBJETIVO: Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. MÉTODOS: O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. RESULTADOS: A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). CONCLUSÃO: Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Obesity increased the risk of SARS-CoV-2 positivity in children.

AIM: To determine the effects of obesity in childhood on SARS-CoV-2 infection. METHODS: A population-based, cross-sectional study combining the Israeli Growth Survey and COVID-19 data for children with at least one SARS-CoV-2 test from 16 February 2020 to 20 December 2021. Overweight and obesity status were based on body mass index and the Center for Disease Control criteria. Multivariate logistics regression was performed to validate reliability for weight categories at the age of approximately 6 years compared with weights at approximately 12 years. RESULTS: A total of 444 868 records for children with an overall positivity rate of 22% were studied. The mean age was 9.5 years. The odds ratios of children with obesity or overweight after controlling for sex at 6 years to test positive were 1.07-1.12 and 1.06-1.08 (depending on the model), respectively, compared to those with healthy range body mass index. CONCLUSION: Excess weight appears to increase the risk of SARS-CoV-2 infection. This finding should be considered for public health planning. For example, children with overweight and obesity should be prioritised for vaccination. Excess weight in childhood can be harmful at a young age and not only for long-term health.

Feeding intolerance during prolonged prone position in overweight and obese patients with severe COVID-19.

Introduction: Objective: the aim of this study was to compare the incidence rate of feeding intolerance (FI) during supine (SP) or prone positioning (PP) in critically ill COVID-19 patients. Methods: this was a retrospective cohort study of critically ill patients with overweight or obesity who received enteral nutrition (EN) in prone or supine positioning continuously during the first five days of mechanical ventilation. Nutritional risk, anthropometric measurements and body composition were assessed at the first 24 hours upon Intensive Care Unit (ICU) admission. Biochemical and clinical variables (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Kidney Injury [AKI] or comorbidities diagnosis) were collected. Pharmacotherapy (prokinetics, sedatives or neuromuscular blocking agents) and FI incidence (gastric residual volume [GRV] ≥ 200 ml or ≥ 500 ml, vomiting or diarrhea) were daily recorded. Constipation was defined as the absence of evacuation for five consecutive days. Results: eighty-two patients were included. Higher rate of prophylactic prokinetic prescription was observed in PP (42.8 vs 12.5 %, p = 0.002). GRV ≥ 200 in supine position was not different when compared to PP (p = 0.47). Vomiting episodes in supine compared to PP showed no difference between groups (15 % vs 24 %, p = 0.31). No differences in diarrhea events were detected (10 % vs 4.7 %, p = 0.36). Constipation was common in both groups (95 % vs 82 %, p = 0.06). Conclusion: FI during prone position was not different in comparison to supine position. Routinely use of prokinetics in continuous prone position may help to prevent FI incidence. Algorithm development is necessary for FI prevention and treatment so to avoid EN interruptions and adverse clinical outcomes.

Introducción: Objetivo: comparar la incidencia de intolerancia a la alimentación entre pacientes críticos en posición supino (PS) o prono (PP). Métodos: cohorte retrospectiva de pacientes bajo ventilación mecánica por distrés respiratorio por COVID-19 y sobrepeso y obesidad, quienes recibieron nutrición enteral (NE) en PP o PS. Se evaluaron riesgo nutricional, mediciones antropométricas y composición corporal en las primeras 24 horas de ingreso a la Unidad de Cuidados Intensivos (UCI). Se recolectaron variables bioquímicas y clínicas (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], lesión renal aguda y otras comorbilidades). Se registró el esquema de farmacoterapia prescrita durante los primeros cinco días (procinéticos, sedantes y bloqueadores neuromusculares). Se evaluó la incidencia de intolerancia a la alimentación, definida como la presencia de residuo gástrico (RG) ≥ 200 o ≥ 500 ml, vómito, diarrea o estreñimiento. Resultados: fueron incluidos 82 pacientes. Se observó una mayor prescripción de procinéticos como terapia profiláctica en PP (42,8 vs. 12,5 %, p = 0,002). No se observaron diferencias en RG ≥ 200 ml (p = 0,47) ni vómito (p = 0,31) entre ambos grupos. No se observaron diferencias en episodios de diarrea (10 % en PS vs. 4,7 % en PP, p = 0,36). El estreñimiento fue común en ambos grupos de estudio (95 vs. 82 %, p = 0,06). Conclusiones: la PP no se relaciona con una mayor incidencia de intolerancias a la alimentación. El uso rutinario de procinéticos durante la PP continua puede ayudar a prevenir la incidencia de dichas intolerancias. Es necesario el desarrollo de algoritmos para la prevención y tratamiento de las intolerancias a la alimentación para evitar interrupciones en la NE y desenlaces no deseables.

Mediterranean diet in the management and prevention of obesity.

The current pandemic of obesity represents a major global public health problem, mainly due to its association with chronic non-communicable disabling conditions and with increased mortality. Population aging increases the chances of non-communicable chronic diseases allowing a longer exposure to risk factors for these disabling conditions. Obesity is a major risk factor contributing to pathological aging. Numerous epidemiological studies have shown that the risk of death due to cardiovascular disease and cancer increases progressively as overweight and obesity rise. Nutrition research is now focused on the effects of combinations of foods in dietary patterns instead of those of single nutrients or foods. The dietary model with the largest body of evidence of health benefit is that traditionally followed by inhabitants of some Mediterranean countries. There is evidence confirming the inverse association of adhering to Mediterranean diet with overweight and obesity. Four meta-analyses of randomized controlled trials, including up to 16 trials, have shown a greater reduction of body weight and BMI with MedDiet compared to other diets, while a meta-analysis of 7 prospective cohort studies, found a reduced risk of becoming obese and gaining weight over time associated with a higher adherence to MedDiet. This narrative review examines studies reporting inverse associations of a higher adherence to the MedDiet with overweight/obesity and with age-associated chronic diseases related to obesity.

Biomarkers as predictors of mortality in critically ill obese patients with COVID-19 at high altitude.

BACKGROUND: Obesity is a common chronic comorbidity of patients with COVID-19, that has been associated with disease severity and mortality. COVID-19 at high altitude seems to be associated with increased rate of ICU discharge and hospital survival than at sea-level, despite higher immune levels and inflammation. The primary aim of this study was to investigate the survival rate of critically ill obese patients with COVID-19 at altitude in comparison with overweight and normal patients. Secondary aims were to assess the predictive factors for mortality, characteristics of mechanical ventilation setting, extubation rates, and analytical parameters. METHODS: This is a retrospective cohort study in critically ill patients with COVID-19 admitted to a hospital in Quito-Ecuador (2,850 m) from Apr 1, 2020, to Nov 1, 2021. Patients were cathegorized as normal weight, overweight, and obese, according to body mass index [BMI]). RESULTS: In the final analysis 340 patients were included, of whom 154 (45%) were obese, of these 35 (22.7%) were hypertensive and 25 (16.2%) were diabetic. Mortality in obese patients (31%) was lower than in the normal weight (48%) and overweight (40%) groups, but not statistically significant (p = 0.076). At multivariable analysis, in the overall population, older age (> 50 years) was independent risk factor for mortality (B = 0.93, Wald = 14.94, OR = 2.54 95%CI = 1.58-4.07, p < 0.001). Ferritin and the neutrophil/lymphocyte ratio were independent predictors of mortality in obese patients. Overweight and obese patients required more positive and-expiratory pressure compared to normal-weight patients. In obese patients, plateau pressure and mechanical power were significantly higher, whereas extubation failure was lower as compared to overweight and normal weight. CONCLUSIONS: This preliminary study suggests that BMI was not associated with mortality in critically ill patients at high altitude. Age was associated with an increase in mortality independent of the BMI. Biomarkers such as ferritin and neutrophils/lymphocytes ratio were independent predictors of mortality in obese patients with COVID-19 at high altitude.

Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors. OBJECTIVES: To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was from January 2018 to June 2022 (original review searched from inception to January 2018). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions to facilitate weight loss in women with endometrial cancer who are overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall survival and 2. frequency of adverse events. Our secondary outcomes were 3. recurrence-free survival, 4. cancer-specific survival, 5. weight loss, 6. cardiovascular and metabolic event frequency and 7. quality of Life. We used GRADE to assess certainty of evidence. We contacted study authors to obtain missing data, including details of any adverse events. MAIN RESULTS: We identified nine new RCTs and combined these with the three RCTs identified in the original review. Seven studies are ongoing.  The 12 RCTs randomised 610 women with endometrial cancer who were overweight or obese. All studies compared combined behavioural and lifestyle interventions designed to facilitate weight loss through dietary modification and increased physical activity with usual care. Included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (withdrawal rate up to 28% and missing data up to 65%, largely due to the effects of the COVID-19 pandemic). Importantly, the short duration of follow-up limits the directness of the evidence in evaluating the impact of these interventions on any of the survival and other longer-term outcomes.  Combined behaviour and lifestyle interventions were not associated with improved overall survival compared with usual care at 24 months (risk ratio (RR) mortality, 0.23, 95% confidence interval (CI) 0.01 to 4.55, P = 0.34; 1 RCT, 37 participants; very low-certainty evidence). There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as the studies reported no cancer-related deaths, myocardial infarctions or strokes, and there was only one episode of congestive heart failure at six months (RR 3.47, 95% CI 0.15 to 82.21; P = 0.44, 5 RCTs, 211 participants; low-certainty evidence). Only one RCT reported recurrence-free survival; however, there were no events. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six or 12 months compared with usual care (at six months: mean difference (MD) -1.39 kg, 95% CI -4.04 to 1.26; P = 0.30, I2 = 32%; 5 RCTs, 209 participants; low-certainty evidence). Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using 12-item Short Form (SF-12) Physical Health questionnaire, SF-12 Mental Health questionnaire, Cancer-Related Body Image Scale, Patient Health Questionnaire 9-Item Version or Functional Assessment of Cancer Therapy - General (FACT-G) at 12 months when compared with usual care (FACT-G: MD 2.77, 95% CI -0.65 to 6.20; P = 0.11, I2 = 0%; 2 RCTs, 89 participants; very low-certainty evidence). The trials reported no serious adverse events related to weight loss interventions, for example hospitalisation or deaths. It is uncertain whether lifestyle and behavioural interventions were associated with a higher or lower risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17 to 310.52; P = 0.04; 8 RCTs, 315 participants; very low-certainty evidence; note: 7 studies reported musculoskeletal symptoms but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 8).  AUTHORS' CONCLUSIONS: The inclusion of new relevant studies has not changed the conclusions of this review. There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life or significant weight loss in women with a history of endometrial cancer who are overweight or obese compared to those receiving usual care. The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, and it is uncertain if musculoskeletal problems were increased, as only one out of eight studies reporting this outcome had any events. Our conclusion is based on low- and very low-certainty evidence from a small number of trials and few women. Therefore, we have very little confidence in the evidence: the true effect of weight-loss interventions in women with endometrial cancer and obesity is currently unknown. Further methodologically rigorous, adequately powered RCTs are required with follow-up of five to 10 years of duration. These should focus on the effects of varying dietary modification regimens, and pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

Premature cardiovascular disease mortality with overweight and obesity as a risk factor: estimating excess mortality in the United States during the COVID-19 pandemic.

BACKGROUND: The United States has experienced high levels of excess mortality during the COVID-19 pandemic and also has high prevalence of overweight and obesity, which increases the risk of severe infection and death from the virus. This study uses multiple cause of death data to estimate excess premature cardiovascular disease mortality in the USA in 2020 for which overweight and obesity was a risk factor. METHODS: The contribution of overweight and obesity to premature (35-74 years) cardiovascular disease mortality was measured as cardiovascular disease reported on the death certificate with one or more of diabetes, chronic kidney disease, obesity, lipidemias or hypertensive heart disease (DKOLH-CVD). Excess mortality was calculated as the difference between actual and expected age-standardised death rates. Expected deaths were estimated using negative binomial regressions of monthly deaths during 2010-19. RESULTS: Excess DKOLH-CVD mortality in March-December 2020 was 29% (95% uncertainty interval 28-31%) for males and 30% (28-32%) for females, much higher than for all causes (males 19% (18-21%), females 16% (14-17%)). Excess mortality was higher where two or more DKOLH conditions (males 40% (37-43%), females 41% (37-44%)) or obesity (males 42% (38-45%), females 47% (43-51%)) were reported. One-half of excess DKOLH-CVD mortality was reported as due to COVID-19, lower than the four-fifths of excess all-cause deaths. For home deaths, just over 10% of excess mortality for each cause classification was reported as due to COVID-19. CONCLUSIONS: Excess premature cardiovascular disease mortality in the USA for which overweight and obesity was a risk factor was considerably higher than for all causes, exacerbating adverse pre-pandemic trends. The contribution of COVID-19 to excess mortality appears significantly under-reported for home deaths.

Television Viewing Time, Overweight, Obesity, and Severe COVID-19: A Brief Report From UK Biobank.

BACKGROUND: Overweight and obesity are well-established risk factors for COVID-19 severity; however, less is known about the role of sedentary behaviors such as television (TV) viewing. The purpose of this brief report was to determine whether lower TV viewing time may mitigate the risk of severe COVID-19 in individuals with excess weight. METHODS: We analyzed 329,751 UK Biobank participants to investigate the independent and combined associations of BMI and self-reported TV viewing time with odds of severe COVID-19 (inpatient COVID-19 or COVID-19 death). RESULTS: Between March 16 and December 8, 2020, there were 1648 instances of severe COVID-19. Per 1-unit (hours per day) increase in TV viewing time, the odds of severe COVID-19 increased by 5% (adjusted odds ratio = 1.05, 95% confidence interval = 1.02-1.08). Compared with normal-weight individuals with low (≤1 h/d) TV viewing time, the odds ratios for overweight individuals with low and high (≥4 h/d) TV viewing time were 1.17 (0.89-1.55) and 1.66 (1.31-2.11), respectively. For individuals with obesity, the respective ORs for low and high TV viewing time were 2.18 (1.61-2.95) and 2.14 (1.69-2.73). CONCLUSION: Higher TV viewing time was associated with higher odds of severe COVID-19 independent of BMI and moderate to vigorous physical activity. Additionally, low TV viewing time may partly attenuate the elevated odds associated with overweight, but not obesity.

Telemedicine management of type 2 diabetes mellitus in obese and overweight young and middle-aged patients during COVID-19 outbreak: A single-center, prospective, randomized control study.

OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic severely affected the disease management of patients with chronic illnesses such as type 2 diabetes mellitus (T2DM). This study aimed to assess the effect of telemedicine management of diabetes in obese and overweight young and middle-aged patients with T2DM during the COVID-19 pandemic. METHODS: A single-center randomized control study was conducted in 120 obese or overweight (body mass index [BMI] ≥ 24 kg/m2) young and middle-aged patients (aged 18-55 years) with T2DM. Patients were randomly assigned to the intervention (telemedicine) or control (conventional outpatient clinic appointment) group. After baseline assessment, they were home isolated for 21 days, received diet and exercise guidance, underwent glucose monitoring, and followed up for 6 months. Glucose monitoring and Self-Rating Depression Scale (SDS) scores were evaluated at 22 days and at the end of 3 and 6 months. RESULTS: Ninety-nine patients completed the 6-month follow-up (intervention group: n = 52; control group: n = 47). On day 22, the fasting blood glucose (FBG) level of the intervention group was lower than that of the control group (p < 0.05), and the control group's SDS increased significantly compared with the baseline value (p < 0.05). At the end of 3 months, glycated hemoglobin (HbA1c) and FBG levels in the intervention group decreased significantly compared with those in the control group (p < 0.01). At the end of 6 months, the intervention group showed a significant decrease in postprandial blood glucose, triglyceride, and low-density lipoprotein cholesterol levels as well as waist-to-hip ratio compared with the control group (p < 0.05); moreover, the intervention group showed lower SDS scores than the baseline value (p < 0.05). Further, the intervention group showed a significant reduction in BMI compared with the control group at the end of 3 and 6 months (p < 0.01). CONCLUSION: Telemedicine is a beneficial strategy for achieving remotely supervised blood glucose regulation, weight loss, and depression relief in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04723550.

Obesity and Dysmetabolic Factors among Deceased COVID-19 Adults under 65 Years of Age in Italy: A Retrospective Case-Control Study.

BACKGROUND: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. METHODS: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February-December 2020. Multivariate logistic regression identified the mortality risk factors. RESULTS: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07-14.76), obesity (adjOR 8.58, CI 3.30-22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06-94.22), heart disease (adjOR 17.68, 95% CI 3.80-82.18), cancer (adjOR 13.28, 95% CI 4.25-41.51) and male sex (adjOR 5.24, 95% CI 2.30-11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. CONCLUSION: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals' death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.

COVID-19 and Gestational Diabetes: The Role of Nutrition and Pharmacological Intervention in Preventing Adverse Outcomes.

Pregnant women with GDM affected by COVID-19 seem to be at higher risk of adverse maternal and neonatal outcomes, especially those with overweight or obesity. Good glycemic control seems to be the most effective measure in reducing the risk of GDM and severe COVID-19. For such purposes, the Mediterranean diet, micronutrient supplementation, and physical activity are considered the first line of treatment. Failure to achieve glycemic control leads to the use of insulin, and this clinical scenario has been shown to be associated with an increased risk of adverse maternal and neonatal outcomes. In this review, we explore the current evidence pertaining to the pathogenesis of SARS-CoV-2 leading to the main complications caused by COVID-19 in patients with GDM. We also discuss the incidence of complications caused by COVID-19 in pregnant women with GDM according to their treatment.

Usage of mobile health interventions among overweight/obese PCOS patients undergoing assisted reproductive technology treatment during the COVID-19 pandemic.

Objective: In the context of the coronavirus disease 2019 (COVID-19) pandemic, telemedicine is a promising tool for providing clinical care for patients. Since the first-line treatment for infertile women with polycystic ovarian syndrome (PCOS) is lifestyle modification, a mobile-based service that provides lifestyle modification education would be helpful in the treatment of PCOS patients. In this observational study, the effect of a mobile Health (mHealth) application for lifestyle modification on PCOS patients undergoing assisted reproductive technology (ART) treatment was evaluated.Methods: A total of 79 overweight/obese patients (40 in the paper group and 39 in the WeChat application group) with PCOS from the First Affiliated Hospital of University of Science and Technology of China were enrolled in the study. The changes in the outcomes of BMI and ART treatment were analyzed between the two groups.Results: After three months of intervention, the BMIs in the control and mHealth groups were 24.5 ± 3.3 and 23.7 ± 3.1, respectively. The percentage of patients who lost weight was higher in the WeChat group than in the control group (87.2% vs. 67.5%). Furthermore, PCOS patients in the WeChat group were found to have a higher live birth rate than those in the control group (p = 0.005).Conclusion: Lifestyle modifications for PCOS patients undergoing ART treatment using the WeChat application improved weight loss and oocyte quality. Infertile patients with PCOS were more likely to make lifestyle modifications based on the usage of mobile applications during the COVID-19 pandemic.

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.

BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

Association between obesity and COVID-19 mortality and length of stay in intensive care unit patients in Brazil: a retrospective cohort study.

The present study aimed to evaluate the association between obesity and COVID-19 mortality and length of stay in ICU patients, and how these associations were modified by age groups. We performed a retrospective multicenter cohort study with data obtained from a hospital-based registry. The sample consisted of 8183 ICU hospitalized patients who tested positive for SARS-CoV-2. Cox proportional models were used to evaluate the association between BMI categories and COVID-19 mortality and generalized linear models for the length of stay in the ICU. After adjusting for confounders, those in the younger group with severe obesity had an increased risk of COVID-19 mortality compared to those with normal/overweight (HR 1.27; 95% CI 1.01-1.61). An increased risk of death was also observed for patients with underweight (HR 3.74; 95% CI 1.39-10.07). For patients aged ≥ 60 year, mild/moderate obesity was associated with reduced mortality risk (HR 0.87; 95% CI 0.78-0.97). For the age group < 60 year, the length of stay in ICU for those patients with severe obesity was 35% higher compared to the normal/overweight category (eß 1.35; 95% CI 1.21-1.51). Conversely, for the survivors in the underweight category, the length of stay in ICU was 51% lower compared to the normal/overweight group (eß 0.49; 95% CI 0.31-0.78). In the age group ≥ 60 year, mild/moderate obesity was associated with an increased length of stay in the ICU (eß 1.10; 95% CI 1.01-1.21), adjusting for confounders. These findings could be helpful for health professionals to identify subgroups at higher risk for worse outcomes.

Overweight and obesity are not associated with worse clinical outcomes in COVID-19 patients treated with fixed-dose 6 mg dexamethasone.

OBJECTIVE: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone. METHODS: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020). RESULTS: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25-30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43-1.53) and 0.61 (0.30-1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99-4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity. CONCLUSIONS: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

The bad rainbow of COVID-19 time: effects on glucose metabolism in children and adolescents with obesity and overweight.

BACKGROUND: COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity-related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on children with obesity during the 13 years before and during the COVID-19 pandemic. SUBJECTS/METHODS: Data from 741 children with obesity and overweight were retrieved and clustered into seven groups starting from year 2008-2009 until 2020-2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. RESULTS: Children with overweight and obesity in the COVID-19 restriction group did not present increased values of SDS-Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR), and body mass fat were detected in these children (all P < 0.01). Fasting glycaemia, glucose, and insulin excursions were significantly higher compared to pre- pandemic children (all P < 0.01). Insulin resistance was higher while insulin secretion was lower (all P < 0.01) determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P < 0.002). Furthermore, High-Density Lipoprotein (HDL) cholesterol was significantly lower (P < 0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P = 0.03 and P = 0.02, respectively). CONCLUSIONS: COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in children with obesity and overweight. Urgent strategies are needed in order to reverse COVID-19 restriction measures' effects on glucose and insulin metabolism.

Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study.

BACKGROUND: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England. METHODS: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m2) after vaccination. FINDINGS: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. INTERPRETATION: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease. FUNDING: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.