SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice.

Background: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear. Methods: We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis. Results: Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling. Conclusion: We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

COVID-19 infection manifesting as a severe gastroparesis flare: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which commonly presents with symptoms including fever, cough, and dyspnea. More recently, however, some patients have tested positive for COVID-19 after developing gastrointestinal (GI) symptoms either solely or in conjunction with respiratory symptoms. This may be due to SARS-CoV-2 infection of the GI tract. In patients with chronic GI illnesses, COVID-19 may initially present as a flare of their underlying GI conditions as viruses have historically been implicated in exacerbations of GI disorders, including gastroparesis. PATIENT CONCERNS: We report a case of a 37-year-old female with a history of diabetic gastroparesis who presented to the Emergency Department (ED) with nausea and vomiting similar to her gastroparesis flares. DIAGNOSES: Her symptoms in the ED failed to improve with fluids and anti-emetic medications. After developing a fever, she was tested and found to be positive for COVID-19. INTERVENTIONS: She was started on antibiotic, steroid, and antiviral medications. OUTCOMES: Her symptoms improved, her fever defervesced on day 4 of hospitalization, and she was discharged on day 5 of hospitalization. The patient reported symptom improvement at a follow-up outpatient gastroenterology visit 2 months after hospitalization. LESSONS: To the best of our knowledge, at the present time, this is the first report of a patient with COVID-19 presenting with signs and symptoms of a gastroparesis flare. This case illustrates that COVID-19 may present in an exacerbation of symptoms of an underlying disorder, such as a severe gastroparesis flare, in a patient with underlying gastroparesis. Initial presentation of these patients manifesting as a flare of their chronic GI disease, more severe than usual, should prompt an index of suspicion for COVID-19.

Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia.

Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

High prevalence of Afro-Caribbean ethnicity and hypoglycaemia in patients with diabetes and end stage renal disease hospitalized with COVID-19.

End stage renal disease (ESRD) is associated with a high mortality rate among patients hospitalized with COVID-19. To the best of our knowledge, there is limited data on the clinical features, ethnicity, inpatient glycaemic control and outcomes in patients with diabetes related ESRD in the literature. We report the clinical features and outcomes of 39 consecutive ESRD patients (28 on haemodialysis [HD] and 11 with renal transplant) secondary to diabetic kidney disease admitted to a university hospital with COVID-19. We observed a high prevalence of patients of Afro-Caribbean ethnicity hospitalized with COVID-19 with a 73% and 54% prevalence in renal transplant and HD groups respectively. The mortality rate of our cohort was 36%. Nearly a one-third of HD patients and one-fifth of transplant patients had hypoglycaemic events during COVID-19 hospitalization. Adjustment of diabetes treatment was frequently required. Our data highlight the importance of integrated multidisciplinary care of patients with diabetes related ESRD hospitalized with COVID-19.

Comorbid diabetes and the risk of disease severity or death among 8807 COVID-19 patients in China: A meta-analysis.

AIMS: Diabetes mellitus has been reported to be one of the most prevalent comorbidity in patients with Coronavirus Disease 2019 (COVID-19). We aimed to assess the association of comorbid diabetes with COVID-19 severity or mortality in China. METHODS: We performed a systematic literature search from six electronic databases on diabetes and COVID-19. The outcome of interest was disease severity or mortality. Heterogeneity among the studies was assessed by the Cochran Q test and the I2 statistic. A random effects model was applied to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). RESULTS: Nine studies from different provinces/cities were identified according to the predefined inclusion and exclusion criteria. There were a total of 1070 patients with diabetes, out of the 8807 COVID-19 cases. The majority of the cases were derived from Hubei Province. A low degree of heterogeneity in the risk estimates was observed in the included studies. Meta-analysis showed that there was a significant association of preexisting diabetes with disease severity or death. The pooled RR was 2.96 (95% CI: 2.31-3.79; p < 0.001). Sensitivity analysis demonstrated no significant changes in the pooled estimates. CONCLUSIONS: Comorbid diabetes was associated with an increased risk of disease severity or death in Chinese COVID-19 patients.

Imminent risk of COVID-19 in diabetes mellitus and undiagnosed diabetes mellitus patients.

Diabetes mellitus is a non-infectious disease and has affected about 425 million adults globally and nearly 15.9 million of them reside in Africa. Moreover, the prevalence of undiagnosed diabetes mellitus is very high in Africa and approximates to around 62%. Nearly 75% of the total deaths due to diabetes are in individuals lesser than 60 years of age. The multifaceted disease of diabetes mellitus produces chronic complications such as, neuropathy, nephropathy, retinopathy, microangiopathy etc. These patients of diabetes mellitus are more susceptible to infections due to compromised immune system. Hence these patients of diabetes mellitus and undiagnosed diabetes mellitus are at greater risk of contracting COVID-19 infections. The dual impact of pathophysiology of COVID-19 infections in diabetes mellitus may increase morbidity and mortality in these patients. Hence there is need of health awareness in diabetics as well in the high-risk group for diabetes such as persons with hypertension and obesity. The scarcity of health resources, shortage of trained medical personnel and disease burden of infectious and non-infectious diseases has laid a heavy impact on the economy in Africa and this has been further strained due to the COVID-19 pandemic. The practice of preventive measures by the risk group of Undiagnosed Diabetes Mellitus patients will prevent them from getting infected by COVID-19 and at the same time decrease mortality rates and hence the undiscovered group that is the patients of undiagnosed diabetes mellitus needs to be vigilant regarding safe preventive practices.

Dissecting the interaction between COVID-19 and diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.

Diabetes and covid-19: more than the sum of two morbidities.

The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.

Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

Convalescent plasma: A possible treatment protocol for COVID- 19 patients suffering from diabetes or underlying liver diseases.

BACKGROUND & AIM: As on date, no specific treatment is available for devastating COVID-19 (SARS-CoV-2) infection. This pandemic viral infection has affected over 200 countries within a very short time and created a calamitous situation across the globe. As per WHO guidelines, the treatment is mainly symptomatic and supportive. This clinical protocol has not proven sufficient to save the lives of COVID-19 patients suffering from diabetes or having underlying liver diseases; hence there is utmost need to tackle this situation by other means such as Convalescent Plasma (CP) therapy. METHODS: A comprehensive literature survey was carriedout using Elsevier, PubMed, Taylor & Francis, Springer, Nature and Google search engines. RESULTS: The patients suffering from diabetes or liver dysfunction or any other underlying diseases are at greatest risk of SARS-CoV-2 infection. From the study, it is proved that plasma collected from the recovered patients of viral infection has considerable potential to treat the viral disease without the occurrence of adverse effects. CONCLUSION: The CP therapy can be a possible life saving alternative to treat critical COVID-19 patients having diabetes or underlying liver dysfunction. Hence, randomised clinical trials are recommended at the earliest to save the lives of infected individuals of COVID-19.

Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2.

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.