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      Importance of hyperglycemia in COVID-19 intensive-care patients: Mechanism and treatment strategy

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          Highlights

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            COVID-19 patients develop hyperglycemia and related complication.

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            COVID-19 is associated with increased risk for development of diabetes in future.

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            Hyperglycemia is an important factor in all operative periods.

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            Hyperglycemia strongly elevated risk of organs failure, and death.

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            Hyperglycemia is strong predictors of organ failure and mortality rate.

          Abstract

          This review reported that coronavirus disease 2019 (COVID-19) infected patients with short time bed rest or quarantine and airway inflammation are at more risk of developing hyperglycemia and insulin resistance. This condition can induce oxidative stress, decrease immune system function, impair endothelial function, induce apoptosis, and reduce antioxidant in the lungs. We provide a possible mechanism in severe COVID-19 patients and recommend treatment strategy to reduce mortality rate and prevent adverse outcomes after intensive care unit (ICU).

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          Covid-19 in Critically Ill Patients in the Seattle Region — Case Series

          Pavan K. Bhatraju, Bijan J Ghassemieh, Michelle Nichols … (2020)
          Abstract Background Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. Methods We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. Results We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. Conclusions During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)
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            Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System

            Mahmoud Gheblawi, Kaiming Wang, Anissa Viveiros … (2020)
            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.
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              Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

              William Grant, Henry Lahore, Sharon McDonnell … (2020)
              The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Prim Care Diabetes
                Journal ID (iso-abbrev): Prim Care Diabetes
                Title: Primary Care Diabetes
                Publisher: Primary Care Diabetes Europe. Published by Elsevier Ltd.
                ISSN (Print): 1751-9918
                ISSN (Electronic): 1878-0210
                Publication date PMC-release: 9 January 2021
                Publication date (Electronic): 9 January 2021
                Affiliations
                [a ]Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
                [b ]Department of Anatomical Sciences, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
                [c ]Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran
                [d ]Islamic Azad University of Sanandaj, Department of Biology, Sanandaj, Iran
                [e ]Hearing Impairment Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
                Author notes
                [* ]Corresponding author at: Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
                Article
                Publisher Item ID: S1751-9918(21)00002-4
                DOI: 10.1016/j.pcd.2021.01.002
                PMC ID: 7834268
                PubMed ID: 33436320
                SO-VID: 8b63fd10-ca40-4f47-b3ab-6a47c4045aba
                Copyright © © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date accepted : 4 January 2021
                Categories
                Subject: Review

                Keywords: coronavirus,covid-19,diabetes,hyperglycemia,oxidative stress,sars-cov-2
                Data availability:
                Keywords: coronavirus, covid-19, diabetes, hyperglycemia, oxidative stress, sars-cov-2

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