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1.
Lancet Diabetes Endocrinol ; 9(9): 586-594, 2021 09.
Article in English | MEDLINE | ID: covidwho-1545532

ABSTRACT

BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.


Subject(s)
Benzhydryl Compounds/administration & dosage , COVID-19/complications , Cardiometabolic Risk Factors , Glucosides/administration & dosage , Multiple Organ Failure/prevention & control , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Multiple Organ Failure/complications , Treatment Outcome
2.
BMJ Open ; 11(9): e051359, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1394121

ABSTRACT

OBJECTIVE: To assess the association of cardiometabolic risk factors with hospitalisation or death due to COVID-19 in the general population. DESIGN, SETTING AND PARTICIPANTS: Swedish population-based cohort including 29 955 participants. EXPOSURES: Cardiometabolic risk factors assessed between 2014 and 2018. MAIN OUTCOME MEASURES: Hospitalisation or death due to COVID-19, as registered in nationwide registers from 31 January 2020 through 12 September 2020. Associations of cardiometabolic risk factors with the outcome were assessed using logistic regression adjusted for age, sex, birthplace and education. RESULTS: Mean (SD) age was 61.2 (4.5) and 51.5% were women. 69 participants experienced hospitalisation or death due to COVID-19. Examples of statistically significant associations between baseline factors and subsequent hospitalisation or death due to COVID-19 included overweight (adjusted OR (aOR) vs normal weight 2.73 (95% CI 1.25 to 5.94)), obesity (aOR vs normal weight 4.09 (95% CI 1.82 to 9.18)), pre-diabetes (aOR vs normoglycaemia 2.56 (95% CI 1.44 to 4.55)), diabetes (aOR vs normoglycaemia 3.96 (95% CI 2.13 to 7.36)), sedentary time (aOR per hour/day increase 1.10 (95% CI 1.02 to 1.17)), grade 2 hypertension (aOR vs normotension 2.44 (95% CI 1.10 to 5.44)) and high density lipoprotein cholesterol (aOR per mmol/L increase 0.33 (95% CI 0.17 to 0.65)). Statistically significant associations were not observed for grade 1 hypertension (aOR vs normotension 1.03 (95% CI 0.55 to 1.96)), current smoking (aOR 0.56 (95% CI 0.24 to 1.30)), total cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.71 to 1.13)), low density lipoprotein cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.69 to 1.15)) and coronary artery calcium score (aOR per 10 units increase 1.00 (95% CI 0.99 to 1.01)). CONCLUSIONS: In a large population-based sample from the general population, several cardiometabolic risk factors were associated with hospitalisation or death due to COVID-19.


Subject(s)
COVID-19 , Cardiometabolic Risk Factors , Cohort Studies , Female , Hospitalization , Humans , Risk Factors , SARS-CoV-2 , Sweden/epidemiology
3.
BMC Cardiovasc Disord ; 21(1): 332, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1344072

ABSTRACT

Recently, we face a surge in the fast-forward Coronavirus Disease 2019 (COVID-19) pandemic with nearly 170 million confirmed cases and almost 3.5 million confirmed deaths at the end of May 2021. Obesity, also known as the pandemic of the 21st century, has been evolving as an adverse prognostic marker. Obesity is associated with a higher risk of being SARS-CoV-2-positive (46%), as well as hospitalization (113%) and death (48%) due to COVID-19. It is especially true for subjects with morbid obesity. Also, observational studies suggest that in the case of COVID-19, no favorable "obesity paradox" is observed. Therefore, it is postulated to introduce a new entity, i.e., coronavirus disease-related cardiometabolic syndrome (CIRCS). In theory, it applies to all stages of COVID-19, i.e., prevention, acute proceedings (from COVID-19 diagnosis to resolution or three months), and long-term outcomes. Consequently, lifestyle changes, glycemic control, and regulation of the renin-angiotensin-aldosterone pathway have crucial implications for preventing and managing subjects with COVID-19. Finally, it is crucial to use cardioprotective drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and statins. Nevertheless, there is the need to conduct prospective studies and registries better to evaluate the issue of obesity in COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , COVID-19/diagnosis , COVID-19/therapy , Cardiometabolic Risk Factors , Diet/adverse effects , Exercise , Hospitalization , Humans , Metabolic Syndrome/diagnosis , Metabolic Syndrome/therapy , Obesity/diagnosis , Obesity/therapy , Physical Distancing , Preventive Health Services , Prognosis , Risk Assessment , Sedentary Behavior
4.
BMC Endocr Disord ; 21(1): 144, 2021 Jul 03.
Article in English | MEDLINE | ID: covidwho-1295459

ABSTRACT

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


Subject(s)
Adiposity/physiology , COVID-19/mortality , Cardiovascular Diseases/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , Aged , Aged, 80 and over , Biological Specimen Banks/statistics & numerical data , Body Mass Index , COVID-19/complications , COVID-19/pathology , Cardiometabolic Risk Factors , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Cohort Studies , Databases, Factual , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/mortality , Female , Hospital Mortality , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/mortality , Middle Aged , Morbidity , Mortality , Obesity/complications , Obesity/mortality , Risk Factors , SARS-CoV-2/physiology , United Kingdom/epidemiology
5.
J Endocrinol Invest ; 44(12): 2845-2847, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1242833

ABSTRACT

PURPOSE: COVID-19 pandemics and cardiometabolic health are mutually interconnected. Chronic metabolic diseases are known risk factors for increased mortality after SARS-CoV-2 infection. In turn, COVID pandemics imposed sudden changes in lifestyle and social isolation with consequent potential cardiometabolic sequelae. The present study aimed at investigating the impact of changes in lifestyle and social life on metabolic profile in hyperprolactinemic or osteoporotic patients without pre-existing cardiometabolic diseases at the time of COVID-19. METHODS: The primary study outcome measurement was the prevalence of obesity, arterial hypertension, impaired glucose tolerance (IGT) or diabetes mellitus (DM), dyslipidemia and metabolic syndrome after COVID-19 outbreak. Seventy-four patients (21 men and 53 women, aged 51.8 ± 17.8 years) were admitted to the outpatient clinic of the Neuroendocrine Disease Unit at University "Federico II" of Naples, Italy, as per their routine clinical practice because of tumoral and non-tumoral hyperprolactinemia in 52 patients (70.3%), and osteoporosis/osteopenia in 22 (29.7%). Among female patients, 25 (47.2%) were at menopausal age. RESULTS: At the end of lockdown, prevalence of obesity (from 37.8% to 51.3%, p < 0.0001), dyslipidemia (from 28.4 to 48.6%, p = 0.003) and metabolic syndrome (from 14.9 to 27%, p < 0.0001) significantly increased compared to pre-COVID evaluation. No significant change was found in the prevalence of arterial hypertension and IGT/DM. CONCLUSION: SARS-CoV-2 outbreak has led to a rapid increase in the prevalence of metabolic syndrome, potentially contributing to the increased COVID-19 related mortality.


Subject(s)
COVID-19 , Cardiometabolic Risk Factors , Metabolic Syndrome/epidemiology , Pandemics , Quarantine , Adult , Aged , Aged, 80 and over , Dyslipidemias/epidemiology , Female , Health Status , Humans , Hyperprolactinemia/complications , Italy/epidemiology , Life Style , Male , Middle Aged , Obesity/epidemiology , Osteoporosis/complications , Prevalence , Social Environment
7.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171152

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
8.
PLoS One ; 16(4): e0248602, 2021.
Article in English | MEDLINE | ID: covidwho-1167090

ABSTRACT

BACKGROUND: SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. OBJECTIVE: This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. METHODS: We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. RESULTS: Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. CONCLUSION: Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.


Subject(s)
COVID-19/epidemiology , Cardiometabolic Risk Factors , Diabetes Mellitus, Type 2/epidemiology , Aged , Apolipoprotein A-I/analysis , Apolipoprotein B-100/analysis , Biological Specimen Banks , Biomarkers/analysis , Body Mass Index , Cholesterol, HDL/analysis , Cholesterol, LDL/analysis , Female , Glycated Hemoglobin A/analysis , Humans , Male , Middle Aged , Triglycerides/analysis , United Kingdom
9.
Glob Heart ; 16(1): 15, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1145668

ABSTRACT

Background: SARS-CoV-2 pandemic has modified the cardiovascular care of ambulatory patients. The aim of this survey was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19. Methods: A cross-sectional survey was conducted in ambulatory patients with cardiometabolic disease using paper/digital surveys. Variables investigated included socioeconomic status, physical activity, diet, tobacco use, alcohol intake, treatment discontinuation, and psychological symptoms. Results: A total of 4,216 patients (50.9% males, mean age 60.3 ± 15.3 years old) from 13 Spanish-speaking Latin American countries were enrolled. Among the study population, 46.4% of patients did not have contact with a healthcare provider, 31.5% reported access barriers to treatments and 17% discontinued some medication. Multivariate analysis showed that non-adherence to treatment was more prevalent in the secondary prevention group: peripheral vascular disease (OR 1.55, CI 1.08-2.24; p = 0.018), heart failure (OR 1.36, CI 1.05-1.75; p = 0.017), and coronary artery disease (OR 1.29 CI 1.04-1.60; p = 0.018). No physical activity was reported by 38% of patients. Only 15% of patients met minimum recommendations of physical activity (more than 150 minutes/week) and vegetable and fruit intake. Low/very low income (45.5%) was associated with a lower level of physical activity (p < 0.0001), less fruit and vegetables intake (p < 0.0001), more tobacco use (p < 0.001) and perception of depression (p < 0.001). Low educational level was also associated with the perception of depression (OR 1.46, CI 1.26-1.70; p < 0.01). Conclusions: Patients with cardiometabolic disease but without clinical evidence of COVID-19 showed significant medication non-adherence, especially in secondary prevention patients. Deterioration in lifestyle habits and appearance of depressive symptoms during the pandemic were frequent and related to socioeconomic status.


Subject(s)
COVID-19 , Cardiovascular Diseases/therapy , Depression/psychology , Diabetes Mellitus/therapy , Diet , Dyslipidemias/therapy , Exercise , Treatment Adherence and Compliance/statistics & numerical data , Adult , Aged , Alcohol Drinking/epidemiology , Arrhythmias, Cardiac/therapy , Cardiometabolic Risk Factors , Cigarette Smoking/epidemiology , Coronary Artery Disease/therapy , Educational Status , Female , Health Services Accessibility , Heart Failure/therapy , Humans , Hypertension/therapy , Latin America/epidemiology , Male , Mental Health , Middle Aged , Outpatients , Peripheral Vascular Diseases/therapy , SARS-CoV-2 , Secondary Prevention , Social Class , Surveys and Questionnaires
10.
PLoS Med ; 18(3): e1003553, 2021 03.
Article in English | MEDLINE | ID: covidwho-1117467

ABSTRACT

BACKGROUND: Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. METHODS AND FINDINGS: We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10-8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10-5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10-5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null. CONCLUSIONS: In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.


Subject(s)
Body Mass Index , COVID-19 , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Disease Susceptibility , Obesity , Renal Insufficiency, Chronic , Stroke , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/genetics , Cardiometabolic Risk Factors , Causality , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genetic Variation , Genome-Wide Association Study/statistics & numerical data , Humans , Mendelian Randomization Analysis , Meta-Analysis as Topic , Obesity/diagnosis , Obesity/epidemiology , Obesity/metabolism , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , SARS-CoV-2 , Severity of Illness Index , Stroke/epidemiology , Stroke/genetics
11.
Am J Med Sci ; 361(6): 718-724, 2021 06.
Article in English | MEDLINE | ID: covidwho-1084611

ABSTRACT

BACKGROUND: Inflammation can facilitate development of coronavirus disease 2019 (COVID-19) and cardiac injury is associated with worse clinical outcomes. However, data are relatively scarce on the association between hyper-inflammatory response and cardiac injury among COVID-19 patients. METHODS: The study was designed based on severe and critically ill patients with COVID-19. Information on clinical characteristics and laboratory examinations was collected from the electronic medical records and analyzed. RESULTS: There were 32.4% (n = 107) of patients with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, and leukocyte counts, significantly elevated concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and inflammatory cytokines. Logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury. CONCLUSIONS: Cardiac injury was associated with elevated levels of inflammatory cytokines among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.


Subject(s)
COVID-19 , Heart Diseases , SARS-CoV-2 , Troponin I/blood , Aged , C-Reactive Protein/analysis , COVID-19/immunology , COVID-19/physiopathology , COVID-19/therapy , Cardiometabolic Risk Factors , China/epidemiology , Critical Illness/epidemiology , Critical Illness/therapy , Diabetes Mellitus/epidemiology , Female , Heart Diseases/diagnosis , Heart Diseases/immunology , Heart Diseases/virology , Humans , Hypertension/epidemiology , Interleukin-6/blood , Male , Risk Assessment , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/virology , Tumor Necrosis Factor-alpha/blood
12.
Scott Med J ; 66(1): 3-10, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1067034

ABSTRACT

BACKGROUND & AIMS: Though viewed as a critical measure to prevent the spread of the virus, a prolonged homestay may result in unfavourable sedentary behaviour and chronic disease risk. This systematic review focuses on sedentary behaviour resulting from this quarantine period which may elevate the cardiovascular disease risk, obesity, hypertension, cancer and mental health illness. METHODS: Evidence of breaking sedentary behaviour and global recommendations were investigated. Potential unanswered questions regarding sedentary behaviour and physical activity during lockdown were explored. RESULTS: Five systematic reviews and six prospective trials explored the effect of sedentarism affecting chronic disease through potential pathophysiological mechanisms. Sedentary behaviour especially prolonged sitting is found to be a pleiotropic risk factor with altered energy expenditure, adipogenic signalling, immunomodulation, autonomic stability and hormonal dysregulation perpetuating underlying chronic diseases such as obesity, cardiovascular disease, cancer and mental health disorders. CONCLUSION: Breaking sitting and physical activity are found to reverse the adverse effects associated with excessive sitting during the lockdown.


Subject(s)
COVID-19/prevention & control , Cardiovascular Diseases/epidemiology , Communicable Disease Control , Mental Disorders/epidemiology , Obesity/epidemiology , Public Policy , Sedentary Behavior , Cardiometabolic Risk Factors , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Chronic Disease , Exercise , Humans , Mental Disorders/metabolism , Mental Disorders/physiopathology , Neoplasms/epidemiology , Neoplasms/metabolism , Neoplasms/physiopathology , Obesity/metabolism , Obesity/physiopathology , SARS-CoV-2
13.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1039811

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
15.
Cytokine Growth Factor Rev ; 58: 102-110, 2021 04.
Article in English | MEDLINE | ID: covidwho-778706

ABSTRACT

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/etiology , Metabolic Diseases/etiology , SARS-CoV-2/pathogenicity , Toll-Like Receptor 4/physiology , COVID-19/epidemiology , COVID-19/pathology , Cardiometabolic Risk Factors , Cardiovascular Diseases/epidemiology , Comorbidity , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/etiology , Humans , Metabolic Diseases/epidemiology , Multiple Organ Failure/epidemiology , Multiple Organ Failure/etiology , Severity of Illness Index
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