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1.
Nutr Metab Cardiovasc Dis ; 31(9): 2612-2618, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1829287

ABSTRACT

BACKGROUND AND AIMS: Diabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19. METHODS AND RESULTS: Diabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19-1.45], 2.11 [1.83-2.44], 2.45 [1.96-3.07], 1.87 [1.68-2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20-39 years: 1.90 [1.04-3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40-59 years: 3.47 [2.00-5.70] and 5.54 [2.23-12.1], respectively. CONCLUSIONS: These data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.


Subject(s)
COVID-19/etiology , Diabetes Complications/etiology , SARS-CoV-2 , Adult , Age Factors , Aged , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Young Adult
3.
Front Endocrinol (Lausanne) ; 13: 780663, 2022.
Article in English | MEDLINE | ID: covidwho-1731765

ABSTRACT

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.


Subject(s)
COVID-19/complications , Diabetes Complications/virology , Diabetes Mellitus/etiology , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/pathology , Causality , Comorbidity , Diabetes Complications/epidemiology , Diabetes Complications/metabolism , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Humans , Patient Acuity , Risk Factors , SARS-CoV-2/pathogenicity
4.
Int J Med Sci ; 19(2): 402-415, 2022.
Article in English | MEDLINE | ID: covidwho-1662815

ABSTRACT

Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.


Subject(s)
COVID-19/genetics , COVID-19/epidemiology , Comorbidity , Coronary Artery Disease/complications , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Diabetes Complications/epidemiology , Diabetes Complications/genetics , Humans , Hypertension/complications , Hypertension/epidemiology , Hypertension/genetics , Mutation , Protein Interaction Maps
5.
Sci Rep ; 12(1): 1438, 2022 01 26.
Article in English | MEDLINE | ID: covidwho-1655618

ABSTRACT

The protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to the current vaccination or natural infection is a global concern. We aimed to investigate the rate of SARS-CoV-2 infection and its clinical features among infection-naïve, infected, vaccinated, and post-infection-vaccinated individuals. A cohort was designed among icddr,b staff registered for COVID-19 testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Reinfection cases were confirmed by whole-genome sequencing. From 19 March 2020 to 31 March 2021, 1644 (mean age, 38.4 years and 57% male) participants were enrolled; where 1080 (65.7%) were tested negative and added to the negative cohort. The positive cohort included 750 positive patients (564 from baseline and 186 from negative cohort follow-up), of whom 27.6% were hospitalized and 2.5% died. Among hospitalized patients, 45.9% had severe to critical disease and 42.5% required oxygen support. Hypertension and diabetes mellitus were found significantly higher among the hospitalised patients compared to out-patients; risk ratio 1.3 and 1.6 respectively. The risk of infection among positive cohort was 80.2% lower than negative cohort (95% CI 72.6-85.7%; p < 0.001). Genome sequences showed that genetically distinct SARS-CoV-2 strains were responsible for reinfections. Naturally infected populations were less likely to be reinfected by SARS-CoV-2 than the infection-naïve and vaccinated individuals. Although, reinfected individuals did not suffer severe disease, a remarkable proportion of naturally infected or vaccinated individuals were (re)-infected by the emerging variants.


Subject(s)
COVID-19/pathology , Reinfection/epidemiology , Adult , COVID-19/complications , COVID-19/virology , Cohort Studies , Diabetes Complications/pathology , Female , Humans , Hypertension/complications , Male , Middle Aged , RNA, Viral/analysis , RNA, Viral/metabolism , Reinfection/diagnosis , Reinfection/virology , Risk , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Severity of Illness Index , Vaccination/statistics & numerical data
6.
Int J Mol Sci ; 23(2)2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1624913

ABSTRACT

Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Pancreas/virology , Pancreatitis/complications , Angiotensin-Converting Enzyme 2/metabolism , Diabetes Complications , Diabetes Mellitus , Humans , Middle East Respiratory Syndrome Coronavirus , Pancreas/injuries , Pancreatic Neoplasms/metabolism , Pancreatitis/chemically induced , SARS Virus , Serine Endopeptidases/metabolism , Sodium-Hydrogen Exchangers/metabolism
8.
J Diabetes ; 14(2): 144-157, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1583720

ABSTRACT

BACKGROUND: Diabetes is a cardiometabolic comorbidity that may predispose COVID-19 patients to worse clinical outcomes. This study sought to determine the prevalence of diabetes in hospitalized COVID-19 patients and investigate the association of diabetes severe COVID-19, rate of acute respiratory distress syndrome (ARDS), mortality, and need for mechanical ventilation by performing a systematic review and meta-analysis. METHODS: Individual studies were selected using a defined search strategy, including results up until July 2021 from PubMed, Embase, and Cochrane Central Register of Controlled Trials. A random-effects meta-analysis was performed to estimate the proportions and level of association of diabetes with clinical outcomes in hospitalized COVID-19 patients. Forest plots were generated to retrieve the odds ratios (OR), and the quality and risk assessment was performed for all studies included in the meta-analysis. RESULTS: The total number of patients included in this study was 10 648, of whom 3112 had diabetes (29.23%). The overall pooled estimate of prevalence of diabetes in the meta-analysis cohort was 31% (95% CI, 0.25-0.38; z = 16.09, P < .0001). Diabetes significantly increased the odds of severe COVID-19 (OR 3.39; 95% CI, 2.14-5.37; P < .0001), ARDS (OR 2.55; 95% CI, 1.74-3.75; P = <.0001), in-hospital mortality (OR 2.44; 95% CI, 1.93-3.09; P < .0001), and mechanical ventilation (OR 3.03; 95% CI, 2.17-4.22; P < .0001). CONCLUSIONS: Our meta-analysis demonstrates that diabetes is significantly associated with increased odds of severe COVID-19, increased ARDS rate, mortality, and need for mechanical ventilation in hospitalized patients. We also estimated an overall pooled prevalence of diabetes of 31% in hospitalized COVID-19 patients.


Subject(s)
COVID-19/complications , Diabetes Complications/mortality , COVID-19/mortality , Hospital Mortality , Humans , Prevalence , Respiration, Artificial , Respiratory Distress Syndrome/virology
9.
Am J Emerg Med ; 52: 166-173, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1562396

ABSTRACT

BACKGROUND: We aimed to determine the characteristics, risk factors, and outcomes associated with readmission in COVID-19 patients. METHODS: PubMed, Embase, Web of Science, and Scopus databases were searched to retrieve articles on readmitted COVID-19 patients, available up to September 25, 2021. All studies comparing characteristics of readmitted and non-readmitted COVID-19 patients were included. We also included articles reporting the reasons for readmission in COVID-19 patients. Data were pooled and meta-analyzed using random or fixed-effect models, as appropriate. Subgroup analyses were conducted based on the place and duration of readmission. RESULTS: Our meta-analysis included 4823 readmitted and 63,413 non-readmitted COVID-19 patients. The re-hospitalization rate was calculated at 9.3% with 95% Confidence Interval (CI) [5.5%-15.4%], mostly associated with respiratory or cardiac complications (48% and 14%, respectively). Comorbidities including cerebrovascular disease (Odds Ratio (OR) = 1.812; 95% CI [1.547-2.121]), cardiovascular (2.173 [1.545-3.057]), hypertension (1.608 [1.319-1.960]), ischemic heart disease (1.998 [1.495-2.670]), heart failure (2.556 [1.980-3.300]), diabetes (1.588 [1.443-1.747]), cancer (1.817 [1.526-2.162]), kidney disease (2.083 [1.498-2.897]), chronic pulmonary disease (1.601 [1.438-1.783]), as well as older age (1.525 [1.175-1.978]), male sex (1.155 [1.041-1.282]), and white race (1.263 [1.044-1.528]) were significantly associated with higher readmission rates (P < 0.05 for all instances). The mortality rate was significantly lower in readmitted patients (OR = 0.530 [0.329-0.855], P = 0.009). CONCLUSIONS: Male sex, white race, comorbidities, and older age were associated with a higher risk of readmission among previously admitted COVID-19 patients. These factors can help clinicians and policy-makers predict, and conceivably reduce the risk of readmission in COVID-19 patients.


Subject(s)
COVID-19/complications , COVID-19/therapy , Patient Readmission/statistics & numerical data , Age Factors , Cardiovascular Diseases/complications , Diabetes Complications , Emergency Service, Hospital/statistics & numerical data , Humans , Kidney Diseases/complications , Lung Diseases/complications , Neoplasms/complications , Race Factors , Risk Factors , SARS-CoV-2 , Sex Factors
10.
Front Endocrinol (Lausanne) ; 12: 772865, 2021.
Article in English | MEDLINE | ID: covidwho-1556281

ABSTRACT

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19/complications , COVID-19/drug therapy , Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Aged , Animals , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Comorbidity , Female , Humans , Hyperglycemia/metabolism , Hypertension , Inflammation , Insulin Resistance , Insulin-Secreting Cells/metabolism , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Risk , Risk Factors , SARS-CoV-2
11.
J Med Virol ; 93(12): 6660-6670, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544317

ABSTRACT

With the wide spread of Coronavirus, most people who infected with the COVID-19, will recover without requiring special treatment. Whereas, elders and those with underlying medical problems are more likely to have serious illnesses, even be threatened with death. Many more disciplines try to find solutions and drive master plan to this global trouble. Consequently, by taking one particular population, Hungary, this study aims to explore a pattern of COVID-19 victims, who suffered from some underlying conditions. Age, gender, and underlying medical problems form the structure of the clustering. K-Means and two step clustering methods were applied for age-based and age-independent analysis. Grouping of the deaths in the form of two different scenarios may highlight some concepts of this deadly disease for public health professionals. Our result for clustering can forecast similar cases which are assigned to any cluster that it will be a serious cautious for the population.


Subject(s)
COVID-19/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Asthma/complications , COVID-19/etiology , Diabetes Complications/epidemiology , Female , Humans , Hungary/epidemiology , Lung Diseases/complications , Male , Middle Aged , Neoplasms/complications , Obesity/complications , Risk Factors , Schizophrenia/complications , Sex Factors , Young Adult
12.
Int J Mol Sci ; 22(22)2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1524023

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...].


Subject(s)
COVID-19/pathology , Cardiovascular Diseases/complications , Diabetes Complications/pathology , COVID-19/complications , COVID-19/virology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Humans , Lipoproteins, LDL/metabolism , SARS-CoV-2/isolation & purification
13.
PLoS Negl Trop Dis ; 15(11): e0009921, 2021 11.
Article in English | MEDLINE | ID: covidwho-1523404

ABSTRACT

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19-induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19-associated mucormycosis in India.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Mucormycosis/epidemiology , Mucormycosis/virology , Antifungal Agents/therapeutic use , COVID-19/microbiology , Coinfection/drug therapy , Coinfection/microbiology , Comorbidity , Diabetes Complications/microbiology , Humans , India/epidemiology , Mucormycosis/drug therapy , Risk Factors
15.
Transl Res ; 241: 52-69, 2022 03.
Article in English | MEDLINE | ID: covidwho-1510374

ABSTRACT

Impaired glucose regulation (IGR) is common world-wide, and is correlated with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus that causes Coronavirus disease 2019 (COVID-19). However, no systematic reviews are available on the topic, and little is known about the strength of the evidence underlying published associations. The current systematic review identified consistent, reproducible associations but several limitations were observed including: (1) a consistent lack of robust confounder adjustment for risk factors collected prior to infection; (2) lack of data on insulin resistance or glycemia measures [Hemoglobin A1c (HbA1c) or glucose]; (3) few studies considering insulin resistance, glucose or HbA1c values in the clinically normal range as a predictor of SARS-CoV-2 risk; (4) few studies assessed the role of IGR as a risk factor for infection among initially uninfected samples; (5) a paucity of population-based data considering SARS-CoV-2 as a risk factor for the onset of IGR. While diabetes status is a clear predictor of poor prognosis following a SARS-CoV-2 infection, causal conclusions are limited. It is uncertain whether interventions targeting dysglycemia to improve SARS-CoV-2 outcomes have potential to be effective, or if risk assessment should include biomarkers of diabetes risk (ie, insulin and glucose or HbA1c) among diabetes-free individuals. Future studies with robust risk factor data collection, among population-based samples with pre-pandemic assessments will be important to inform these questions.


Subject(s)
COVID-19/pathology , Diabetes Complications , Glucose/metabolism , SARS-CoV-2/isolation & purification , COVID-19/complications , COVID-19/virology , Humans , Severity of Illness Index
16.
Inflamm Res ; 71(1): 27-38, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1491057

ABSTRACT

INTRODUCTION: The rapid emergence and spread of SARS-CoV-2 in late 2019 has infected millions of people worldwide with significant morbidity and mortality with various responses from health authorities to limit the spread of the virus. Although population-wide inoculation is preferred, currently, there is large variation and disparity in the acquisition, development, and deployment of vaccination programs in many countries. Even with availability of a vaccine, achieving herd immunity does not guarantee against reinfection from SARS-CoV-2. Emerging evidence indicates that vaccines do not eliminate infection but protect against severe disease and potential hospitalisation. Therefore, additional strategies which strengthen the immune system should be strongly considered to assist in reducing the overall health care burden and stem the rate of infection. There is now substantial evidence that SARS-CoV-2 disease severity and death are linked to existing comorbidities such as cardiovascular disease, obesity, and metabolic disorders. PURPOSE: In this review, we discuss the potential medium-to-long-term strategy of habitual exercise and its relationship to targeted comorbidities and underlying inflammation as a protective mechanism against SARS-CoV-2 disease severity. CONCLUSION: We conclude that engagement in habitual physical activity and exercise could be a strategy to mitigate the development of comorbidities and improve the response of the immune system, potentially reducing the risk of symptoms and life-threatening complications if infected.


Subject(s)
COVID-19/pathology , COVID-19/virology , Exercise Therapy , SARS-CoV-2 , COVID-19/complications , COVID-19 Vaccines , Cardiovascular Diseases/complications , Comorbidity , Cytokine Release Syndrome , Cytokines/metabolism , Diabetes Complications , Exercise , Female , Health Status , Humans , Hypertension/complications , Immune System , Inflammation , Male , Obesity/complications , Risk , Severity of Illness Index
17.
Biomolecules ; 11(11)2021 10 27.
Article in English | MEDLINE | ID: covidwho-1488477

ABSTRACT

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of "clinically" relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, "IV-effects" of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 µg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.


Subject(s)
Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Hemorrhage/prevention & control , S-Nitrosoglutathione/administration & dosage , Stroke/complications , Thrombolytic Therapy/adverse effects , Animals , Behavior, Animal , Blood Pressure , Blood-Brain Barrier , COVID-19/epidemiology , Hemorrhage/complications , Hypoxia , Infusions, Intravenous , Laser-Doppler Flowmetry , Male , Mice , Mice, Inbred C57BL , Microcirculation , Nebulizers and Vaporizers , Neuroprotective Agents/pharmacology , Perfusion , Reperfusion Injury/drug therapy , Risk , Stress, Mechanical
18.
Diabetes Metab Syndr ; 15(6): 102328, 2021.
Article in English | MEDLINE | ID: covidwho-1487693

ABSTRACT

BACKGROUND AND AIMS: Cardiometabolic disease may confer increased risk of adverse outcomes in COVID-19 patients by activation of the aldose reductase pathway. We hypothesized that aldose reductase inhibition with AT-001 might reduce viral inflammation and risk of adverse outcomes in diabetic patients with COVID-19. METHODS: We conducted an open-label prospective phase 2 clinical trial to assess safety, tolerability and efficacy of AT-001 in patients hospitalized with COVID-19 infection, history of diabetes mellitus and chronic heart disease. Eligible participants were prospectively enrolled and treated with AT-001 1500 mg BID for up to 14 days. Safety, tolerability, survival and length of hospital stay (LOS) were collected from the electronic medical record and compared with data from two matched control groups (MC1 and MC2) selected from a deidentified registry of COVID-19 patients at the same institution. RESULTS: AT-001 was safe and well tolerated in the 10 participants who received the study drug. In-hospital mortality observed in the AT-001 group was 20% vs. 31% in MC1 and 27% in MC2. Mean LOS observed in the AT-001 group was 5 days vs. 10 days in MC1 and 25 days in MC2. CONCLUSIONS: In hospitalized patients with COVID-19 and co-morbid diabetes mellitus and heart disease, treatment with AT-001 was safe and well tolerated. Exposure to AT-001 was associated with a trend of reduced mortality and shortened LOS. While the observed trend did not reach statistical significance, the present study provides the rationale for investigating potential benefit of AT-001 in COVID 19 affected patients in future studies.


Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Benzothiazoles/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , Pyridones/therapeutic use , Registries , Aged , Benzothiazoles/pharmacology , COVID-19/complications , COVID-19/mortality , Diabetes Complications/drug therapy , Female , Humans , Hypertension/complications , Inpatients , Male , Middle Aged , New York/epidemiology , Pilot Projects , Prospective Studies , Pyrazines/pharmacology , Pyridones/pharmacology
19.
Diabetes ; 70(12): 2733-2744, 2021 12.
Article in English | MEDLINE | ID: covidwho-1484985

ABSTRACT

The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. COVID-19 may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is unclear whether the virus induces type 1 or type 2 diabetes or instead causes a novel atypical form of diabetes. Moreover, it remains unknown if recovering COVID-19 patients exhibit a higher risk of developing new-onset diabetes or its complications going forward. The aim of this review is to summarize what is currently known about the epidemiology and mechanisms of this bidirectional relationship between COVID-19 and diabetes. We highlight major challenges that hinder the study of COVID-19-induced new-onset of diabetes and propose a potential framework for overcoming these obstacles. We also review state-of-the-art wearables and microsampling technologies that can further study diabetes management and progression in new-onset diabetes cases. We conclude by outlining current research initiatives investigating the bidirectional relationship between COVID-19 and diabetes, some with emphasis on wearable technology.


Subject(s)
COVID-19/complications , Diabetes Mellitus/etiology , SARS-CoV-2 , COVID-19/epidemiology , Diabetes Complications , Diabetes Mellitus/mortality , Humans
20.
Diabetes Metab Syndr ; 15(6): 102322, 2021.
Article in English | MEDLINE | ID: covidwho-1482539

ABSTRACT

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.


Subject(s)
Adrenal Cortex Hormones/adverse effects , COVID-19/complications , Diabetes Complications/virology , Mucormycosis/virology , Adult , Aged , COVID-19/drug therapy , Comorbidity , Diabetes Complications/mortality , Female , Humans , India/epidemiology , Male , Middle Aged , Mucormycosis/chemically induced , Mucormycosis/mortality , Retrospective Studies , Risk Factors
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