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      COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin

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          Abstract

          Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability.

          Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily ( n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone ( n = 20). Anthropometric, biochemical, and radiological data were evaluated.

          Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients ( p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.

          Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.

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          Most cited references50

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          Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes

          Summary Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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            Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19

            Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.
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              SARS2-CoV-2 and Stroke in a New York Healthcare System

              Background and Purpose: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. Methods: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). Results: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. Conclusions: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                19 February 2021
                2021
                19 February 2021
                : 8
                : 644295
                Affiliations
                [1] 1Department of Clinical Pharmacology and Medicine, College of Medicine, Al-Mustansiriyia University , Baghdad, Iraq
                [2] 2Department of Microbiology, College of Medicine, Taif University , Taif, Saudi Arabia
                [3] 3Faculty of Medicine, University of Porto , Porto, Portugal
                [4] 4Institute for Research and Innovation in Health (i3S), University of Porto , Porto, Portugal
                [5] 5Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto , Porto, Portugal
                [6] 6Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University , Damanhour, Egypt
                Author notes

                Edited by: Pierpaolo Di Micco, Ospedale Buon Consiglio Fatebenefratelli, Italy

                Reviewed by: Ciro Salzano, Ospedale Buon Consiglio Fatebenefratelli, Italy; Maria Rita Poggiano, Ospedale Buon Consiglio Fatebenefratelli, Italy

                *Correspondence: Natália Cruz-Martins ncmartins@ 123456med.up.pt
                Gaber El-Saber Batiha gaberbatiha@ 123456gmail.com

                This article was submitted to Hematology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2021.644295
                7944640
                33718411
                2d2538df-16f4-4b86-9008-86693ec9ba30
                Copyright © 2021 Al-kuraishy, Al-Gareeb, Alblihed, Cruz-Martins and Batiha.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 December 2020
                : 22 January 2021
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 50, Pages: 10, Words: 6569
                Categories
                Medicine
                Original Research

                covid-19,acute ischaemic stroke,diabates mellitus,metformin,sars-cov-2

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