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.

Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19.

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

A new interventional home care model for COVID management: Virtual Covid IP.

AIM: Amidst COVID-19 pandemic, the health care delivery in India faces major challenges owing to the overwhelming hospitals, exhausted healthcare workers, and shortage of crucial medical supplies such as ventilators and oxygen. The study aims to propose a novel successful interventional home care model, the Virtual COVID In-Patient (VCIP) care for effective COVID management. METHODS: The Covid-19 positive patients enrolled in VCIP were chosen for the study. A 24/7 active multidisciplinary WhatsApp group was created for each patient, for remote monitoring of temperature, blood pressure, blood glucose, respiratory and pulse rate along with the symptoms. Advice on sleep and exercises were given along with the medication via video-audio consultations. Lab facility was provided at the doorstep. Training on various devices, medications including steroids, delivering subcutaneous injections etc were given via video platforms. RESULTS: Among the 220 patients who availed the VCIP facility, only two were hospitalized, yielding a 99.5 % success rate in preventing hospitalizations and patients enrolled have been immensely satisfied with their experience. CONCLUSIONS: With similar pandemics anticipated in near future, VCIP model may be considered for successful domiciliary treatment and overcoming the challenges.

Hospital admission for type 2 diabetes mellitus under the Universal Coverage Scheme in Thailand: A time- and geographical-trend analysis, 2009-2016.

BACKGROUND: Descriptive analyses of 2009-2016 were performed using the data of the Universal Coverage Scheme (UCS) which covers nearly 70 percent of the Thai population. The analyses described the time and geographical trends of nationwide admission rates of type 2 diabetes mellitus (T2DM) and its complications, including chronic kidney disease (CKD), myocardial infarction, cerebrovascular diseases, retinopathy, cataract, and diabetic foot amputation. METHODS AND FINDINGS: The database of T2DM patients aged 15-100 years who were admitted between 2009 and 2016 under the UCS and that of the UCS population were retrieved for the analyses. The admitted cases of T2DM were extracted from the database using disease codes of principal and secondary diagnoses defined by the International Classification of Diseases 9th and 10th Revisions. The T2DM admission rates in 2009-2016 were the number of admissions divided by the number of the UCS population. The standardized admission rates (SARs)were further estimated in contrast to the expected number of admissions considering age and sex composition of the UCS population in each region. A linearly increased trend was found in T2DM admission rates from 2009 to 2016. Female admission rates were persistently higher than that of males. In 2016, an increase in the T2DM admission rates was observed among the older ages relative to that in 2009. Although the SARs of T2DM were generally higher in Bangkok and central regions in 2009, except that with CKD and foot amputation which had higher trends in northeastern regions, the geographical inequalities were fairly reduced by 2016. CONCLUSION: Admission rates of T2DM and its major complications increased in Thailand from 2009 to 2016. Although the overall geographical inequalities in the SARs of T2DM were reduced in the country, further efforts are required to improve the health system and policies focusing on risk factors and regions to manage the increasing T2DM.

Use of Continuous Glucose Monitor in Critically Ill COVID-19 Patients Requiring Insulin Infusion: An Observational Study.

CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic has created a need for remote blood glucose (BG) monitoring in the intensive care unit (ICU). OBJECTIVE: To evaluate feasibility and patient safety of a hybrid monitoring strategy of point-of-care (POC) BG plus continuous glucose monitor (CGM) in the ICU. DESIGN: Retrospective analysis. SETTING: ICU of an academic medical center. PATIENTS: Patients with COVID-19 on IV insulin. INTERVENTION: After meeting initial validation criteria, CGM was used for IV insulin titration and POC BG was performed every 6 hours or as needed. MAIN OUTCOME MEASURES: Outcomes included frequency of POC BG, workflow, safety, and accuracy measures. RESULTS: The study included 19 patients, 18 with CGM data, mean age 58 years, 89% on mechanical ventilation, 37% on vasopressors, and 42% on dialysis. The median time to CGM validation was 137 minutes (interquartile range [IQR] 114-206). During IV insulin, the median number of POC values was 7 (IQR 6-16) on day 1, and declined slightly thereafter (71% reduction compared with standard of 24/day). The median number of CGM values used nonadjunctively to titrate IV insulin was 11.5 (IQR 0, 15) on day 1 and increased thereafter. Time in range 70 to 180 mg/dL was 64 ± 23% on day 1 and 72 ± 16% on days 2 through 7, whereas time <70 mg/dL was 1.5 ± 4.1% on day 1 and <1% on days 2 through 7. CONCLUSIONS: This study provides data to support that CGM using a hybrid protocol is feasible, accurate, safe, and has potential to reduce nursing and staff workload.

Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Severity of COVID-19 and Treatment Strategy for Patient With Diabetes.

Coronavirus disease 2019 (COVID-19), which was named by the World Health Organization (WHO) in February 2020, has quickly spread to more than 200 countries around the world and was declared as a global pandemic in March 2020. The severity of the disease makes it more prone to severe symptoms and higher mortality rates in patients, especially those who are with comorbidities, including high blood pressure, cardiovascular disease, obesity, and diabetes, increases the concern over the consequences of this pandemic. However, initial reports do not clearly describe whether diabetes itself or associated comorbidities or treatment strategies contribute to the severe prognosis of COVID-19 infections. Various clinical trials are being conducted on glucose-lowering agents but to date, there is no standard treatment protocol approved for COVID-19 cases with pre-existing diabetes. This review is aimed to decipher the potential risk factors of COVID-19 involved from existing evidence. Identification of a novel therapeutic strategy could be beneficial for combating SARS-CoV-2, which might be dreadful to debilitating people who have diabetes.

Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis.

AIMS/HYPOTHESIS: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death. METHODS: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool. RESULTS: A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19. CONCLUSIONS/INTERPRETATION: Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted. REGISTRATION: PROSPERO registration ID CRD42020193692.

Type 2 Diabetes Mellitus and COVID-19: A Narrative Review.

The pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has involved more than one hundred million individuals, including more than two million deaths. Diabetes represents one of the most prevalent chronic conditions worldwide and significantly increases the risk of hospitalization and death in COVID-19 patients. In this review, we discuss the prevalence, the pathophysiological mechanisms, and the outcomes of COVID-19 infection in people with diabetes. We propose a rationale for using drugs prescribed in patients with diabetes and some pragmatic clinical recommendations to deal with COVID-19 in this kind of patient.

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.

When Scarcity Meets Disparity: "Resources Allocation and COVID-19 Patients with Diabetes".

The COVID-19 pandemic raised distinct challenges in the field of scarce resource allocation, a long-standing area of inquiry in the field of bioethics. Policymakers and states developed crisis guidelines for ventilator triage that incorporated such factors as immediate prognosis, long-term life expectancy, and current stage of life. Often these depend upon existing risk factors for severe illness, including diabetes. However, these algorithms generally failed to account for the underlying structural biases, including systematic racism and economic disparity, that rendered some patients more vulnerable to these conditions. This paper discusses this unique ethical challenge in resource allocation through the lens of care for patients with severe COVID-19 and diabetes.

Impact of Diabetes in Patients Diagnosed With COVID-19.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), known as a highly contagious disease, currently affecting more than 200 countries worldwide. The main feature of SARS-CoV-2 that distinguishes it from other viruses is the speed of transmission combined with higher risk of mortality from acute respiratory distress syndrome (ARDS). People with diabetes mellitus (DM), severe obesity, cardiovascular disease, and hypertension are more likely to get infected and are at a higher risk of mortality from COVID-19. Among elderly patients who are at higher risk of death from COVID-19, 26.8% have DM. Although the reasons for this increased risk are yet to be determined, several factors may contribute to type-2 DM patients' increased susceptibility to infections. A possible factor that may play a role in increasing the risk in people affected by diabetes and/or obesity is the impaired innate and adaptive immune response, characterized by a state of chronic and low-grade inflammation that can lead to abrupt systemic metabolic alteration. SARS patients previously diagnosed with diabetes or hyperglycemia had higher mortality and morbidity rates when compared with patients who were under metabolic control. Similarly, obese individuals are at higher risk of developing complications from SARS-CoV-2. In this review, we will explore the current and evolving insights pertinent to the metabolic impact of coronavirus infections with special attention to the main pathways and mechanisms that are linked to the pathophysiology and treatment of diabetes.

Clinical characteristics and outcomes of COVID-19 hospitalized patients with diabetes in the United Kingdom: A retrospective single centre study.

AIM: To describe the clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes. METHODS: A retrospective cross-sectional study was conducted among patients admitted to the William Harvey Hospital in England between March 10th and May10th, 2020 with a laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), known as COVID-19. Variation in characteristics, length of stay in hospital, diabetes status, duration of diabetes, control of diabetes, comorbidities and outcomes were examined. RESULTS: There were 232 COVID-19 presentations. Mean (standard deviation (SD), range) age was 70.5 (±15.7, 30-101) years, 62.5% were male, and 37.5% were having diabetes. There were 43.4% males and 27.6 females, p = 0.016, with diabetes admitted to our hospital due to COVID-19. Patients with diabetes were more likely to have longer length of stay (LOS) in hospital, 14.4 (SD ± 9.6) days, compared to the patients without diabetes, 9.8 (SD ± 17.1) days, p < 0.0001. Patients with diabetic ketoacidosis (DKA) were more likely to survive (87.1%) compared to patients without DKA (50.6%), p = 0.046. CONCLUSION: Males were more likely to be admitted to hospital with COVID-19 illness than females. Hospitalized COVID-19 patients with diabetes had a longer LOS in hospital than patients without diabetes. Older age COVID-19 patients with diabetes and patients without DKA were less likely to survive compared to younger patients and patients with DKA, respectively. Further studies with large sample size are needed.

The Australian response to the COVID-19 pandemic and diabetes - Lessons learned.

The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to "flatten" the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.

Clouds and Silver Linings: COVID-19 Pandemic Is an Opportune Moment to Democratize Diabetes Care Through Telehealth.

With the recent pivot to telehealth as a direct result of the COVID-19 pandemic, there is an imperative to ensure that access to affordable devices and technologies with remote monitoring capabilities for people with diabetes becomes equitable. In addition, expanding the use of remote Diabetes Self-Management Education and Support (DSMES) and Medical Nutrition Therapy (MNT) services will require new strategies for achieving long-term, effective, continuous, data-driven care. The current COVID-19 pandemic has especially impacted underserved US communities that were already disproportionately impacted by diabetes. Historically, these same communities have faced barriers in accessing timely and effective diabetes care including access to DSMES and MNT services, and diabetes technologies. Our call to action encourages all involved to urge US Federal representatives to widen access to the array of technologies necessary for successful telehealth-delivered care beyond COVID-19.